Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

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Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

2018-06-16

Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

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Saman Mohammadi

Full Text Available In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline. The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC, and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001. The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

Removal of the basement membrane enhances corneal wound healing.

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Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Stepp, Mary Ann

2011-12-01

Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, β4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. Copyright © 2011 Elsevier Ltd. All rights reserved.

Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

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2017-02-01

a cell population particularly suitable for low serum propagation, provided that appropriate growth factors are available. A low serum medium...of MGK. 15. SUBJECT TERMS Cornea, chemical warfare agent, corneal endothelial cell, endothelium, growth , isolation, mouse, rabbit, porcine, in...with corneal SM exposure.2 A primary requirement in achieving this goal is to develop methods that enable the isolation of a pure CEC population and

Systematic assessment of microneedle injection into the mouse cornea.

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Matthaei, Mario; Meng, Huan; Bhutto, Imran; Xu, Qingguo; Boelke, Edwin; Hanes, Justin; Jun, Albert S

2012-06-20

Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. A mean corneal area of 5.0 ± 1.4 mm(2) (mean ± SD) and 7.7 ± 1.4 mm(2) was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively of total corneal area involved.

Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals.

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Higuchi, Akihiro; Inoue, Hiroyoshi; Kaneko, Yoshio; Oonishi, Erina; Tsubota, Kazuo

2016-11-11

The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.

Systematic assessment of microneedle injection into the mouse cornea

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Matthaei Mario

2012-06-01

Full Text Available Abstract Background Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Methods Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. Results A mean corneal area of 5.0 ±1.4 mm2 (mean ± SD and 7.7 ±1.4 mm2 was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Conclusions Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively

Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

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Philipp Steven

Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

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Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recovery of Corneal Sensitivity and Increase in Nerve Density and Wound Healing in Diabetic Mice After PEDF Plus DHA Treatment.

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He, Jiucheng; Pham, Thang Luong; Kakazu, Azucena; Bazan, Haydee E P

2017-09-01

Diabetic keratopathy decreases corneal sensation and tear secretion and delays wound healing after injury. In the current study, we tested the effect of treatment with pigment epithelium-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) on corneal nerve regeneration in a mouse model of diabetes with or without corneal injury. The study was performed in streptozotocin-induced diabetic mice (C57BL/6). Ten weeks after streptozotocin injection, diabetic mice showed significant decreases of corneal sensitivity, tear production, and epithelial subbasal nerve density when compared with age-matched normal mice. After diabetic mice were wounded in the right eye and treated in both eyes with PEDF+DHA for 2 weeks, there was a significant increase in corneal epithelial nerve regeneration and substance P-positive nerve density in both wounded and unwounded eyes compared with vehicle-treated corneas. There also was elevated corneal sensitivity and tear production in the treated corneas compared with vehicle. In addition, PEDF+DHA accelerated corneal wound healing, selectively recruited type 2 macrophages, and prevented neutrophil infiltration in diabetic wounded corneas. These results suggest that topical treatment with PEDF+DHA promotes corneal nerve regeneration and wound healing in diabetic mice and could potentially be exploited as a therapeutic option for the treatment of diabetic keratopathy. © 2017 by the American Diabetes Association.

Anatomical characterization of central, apical and minimal corneal thickness

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Federico Saenz-Frances

2014-08-01

Full Text Available AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness (pupil center in relation to the corneal apex.METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex (AT, minimum corneal thickness (MT and corneal thickness at the pupil center (PT were determined using the pentacam. Distances from the corneal apex to MT (MD and PT (PD were calculated and their quadrant position (taking the corneal apex as the reference determined:point of minimum thickness (MC and point of central thickness (PC depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume (determined using the Pentacam and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models.RESULTS: MT was located at a mean distance of 0.909 mm from the apex (79.4% in the inferior-temporal quadrant. PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume (B=-0.024; 95%CI:-0.043 to -0.004. No significant relations were identified in the linear regression model for PD or the multinomial logistic regressions for MC and PC.CONCLUSION: MT was typically located at the inferior-temporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

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Min Gao

Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

A new dry eye mouse model produced by exorbital and intraorbital lacrimal gland excision.

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Shinomiya, Katsuhiko; Ueta, Mayumi; Kinoshita, Shigeru

2018-01-24

Chronic dry eye is an increasingly prevalent condition worldwide, with resulting loss of visual function and quality of life. Relevant, repeatable, and stable animal models of dry eye are still needed. We have developed an improved surgical mouse model for dry eye based on severe aqueous fluid deficiency, by excising both the exorbital and intraorbital lacrimal glands (ELG and ILG, respectively) of mice. After ELG plus ILG excision, dry eye symptoms were evaluated using fluorescein infiltration observation, tear production measurement, and histological evaluation of ocular surface. Tear production in the model mice was significantly decreased compared with the controls. The corneal fluorescein infiltration score of the model mice was also significantly increased compared with the controls. Histological examination revealed significant severe inflammatory changes in the cornea, conjunctiva or meibomian glands of the model mice after surgery. In the observation of LysM-eGFP (+/-) mice tissues, postsurgical infiltration of green fluorescent neutrophils was observed in the ocular surface tissues. We theorize that the inflammatory changes on the ocular surface of this model were induced secondarily by persistent severe tear reduction. The mouse model will be useful for investigations of both pathophysiology as well as new therapies for tear-volume-reduction type dry eye.

Corneal Laceration

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Full Text Available ... Eye Health A-Z Symptoms Glasses & Contacts Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye ... Causes Corneal Laceration? Corneal Laceration Diagnosis Corneal Laceration Treatment What Is Corneal Laceration? Leer en Español: ¿Qué ...

Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

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Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

2010-01-01

We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer

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Hatim Batawi

2016-01-01

Full Text Available Purpose: We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method: This is an observational case report study. Results: A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion: Corneal hydrops can occur in the setting of corneal infections.

Comparison of confocal microscopy and two-photon microscopy in mouse cornea in vivo.

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Lee, Jun Ho; Lee, Seunghun; Gho, Yong Song; Song, In Seok; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

2015-03-01

High-resolution imaging of the cornea is important for studying corneal diseases at cellular levels. Confocal microscopy (CM) has been widely used in the clinic, and two-photon microscopy (TPM) has recently been introduced in various pre-clinical studies. We compared the performance of CM and TPM in normal mouse corneas and neovascularized mouse corneas induced by suturing. Balb/C mice and C57BL/6 mice expressing green fluorescent protein (GFP) were used to compare modalities based on intrinsic contrast and extrinsic fluorescence contrast. CM based on reflection (CMR), CM based on fluorescence (CMF), and TPM based on intrinsic/extrinsic fluorescence and second harmonic generation (SHG) were compared by imaging the same sections of mouse corneas sequentially in vivo. In normal mouse corneas, CMR visualized corneal cell morphologies with some background noise, and CMF visualized GFP expressing corneal cells clearly. TPM visualized corneal cells and collagen in the stroma based on fluorescence and SHG, respectively. However, in neovascularized mouse corneas, CMR could not resolve cells deep inside the cornea due to high background noise from the effects of increased structural irregularity induced by suturing. CMF and TPM visualized cells and induced vasculature better than CMR because both collect signals from fluorescent cells only. Both CMF and TPM had signal decays with depth due to the structural irregularity, with CMF having faster signal decay than TPM. CMR, CMF, and TPM showed different degrees of image degradation in neovascularized mouse corneas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corneal Laceration

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Trifluoperazine: corneal endothelial phototoxicity

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Hull, D.S.; Csukas, S.; Green, K.

1983-01-01

Trifluoperazine is used for the treatment of psychiatric disorders. Perfusion of corneal endothelial cells with trifluoperazine-HC1 concurrent with exposure to long wavelength ultraviolet light resulted in a corneal swelling rate greater than that found in perfused corneas not exposed to ultraviolet light. Exposure of endothelial cells to 25 W incandescent light during perfusion with trifluoperazine-HC1 did not result in a higher corneal swelling rate compared to those perfused in the dark. The increased corneal swelling rate could be produced by pre-exposure of the trifluoperazine-HC1 perfusing solution to ultraviolet light suggesting the production of toxic photoproducts during exposure of trifluoperazine-HC1 to ultraviolet light. Perfusion of corneal endothelial cells with non-ultraviolet illuminated trifluoperazine-HC1 had no effect on endothelial cell membranes or ultrastructure. This is in contrast to cells perfused with trifluoperazine-HC1 that had been exposed to ultraviolet light in which there was an alteration of mitochondria and a loss of cytoplasmic homogeneity. The data imply that the trifluoperazine-HC1 photoproduct had an adverse effect on cellular transport mechanisms. The study also further demonstrates the value of the corneal endothelial cell model for identifying the physiological and anatomical changes occuring in photo-induced toxic reactions. (author)

Role of corneal collagen fibrils in corneal disorders and related pathological conditions

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Hong-Yan Zhou

2017-05-01

Full Text Available The cornea is a soft tissue located at the front of the eye with the principal function of transmitting and refracting light rays to precisely sense visual information. Corneal shape, refraction, and stromal stiffness are to a large part determined by corneal fibrils, the arrangements of which define the corneal cells and their functional behaviour. However, the modality and alignment of native corneal collagen lamellae are altered in various corneal pathological states such as infection, injury, keratoconus, corneal scar formation, and keratoprosthesis. Furthermore, corneal recuperation after corneal pathological change is dependent on the balance of corneal collagen degradation and contraction. A thorough understanding of the characteristics of corneal collagen is thus necessary to develop viable therapies using the outcome of strategies using engineered corneas. In this review, we discuss the composition and distribution of corneal collagens as well as their degradation and contraction, and address the current status of corneal tissue engineering and the progress of corneal cross-linking.

Experimental Models for Investigating Intra-Stromal Migration of Corneal Keratocytes, Fibroblasts and Myofibroblasts

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Lisha Ma

2012-03-01

Full Text Available Following laser vision correction, corneal keratocytes must repopulate areas of cell loss by migrating through the intact corneal stroma, and this can impact corneal shape and transparency. In this study, we evaluate 3D culture models for simulating this process in vitro. Buttons (8 mm diameter were first punched out of keratocyte populated compressed collagen matrices, exposed to a 3 mm diameter freeze injury, and cultured in serum-free media (basal media or media supplemented with 10% FBS, TGFb1 or PDGF BB. Following freeze injury, a region of cell death was observed in the center of the constructs. Although cells readily migrated on top of the matrices to cover the wound area, a limited amount of cell migration was observed within the constructs. We next developed a novel “sandwich” model, which better mimics the native lamellar architecture of the cornea. Using this model, significant migration was observed under all conditions studied. In both models, cells in TGFb and 10% FBS developed stress fibers; whereas cells in PDGF were more dendritic. PDGF stimulated the most inter-lamellar migration in the sandwich construct. Overall, these models provide insights into the complex interplay between growth factors, cell mechanical phenotypes and the structural properties of the ECM.

Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model

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Li, Xinyu; Zhou, Qinbo; Hanus, Jakub; Anderson, Chastain; Zhang, Hongmei; Dellinger, Michael; Brekken, Rolf; Wang, Shusheng

2013-01-01

Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders. PMID:23186311

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model.

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Zhang, Wei; Chen, Jialin; Backman, Ludvig J; Malm, Adam D; Danielson, Patrik

2017-03-01

The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm -1 optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Corneal tissue welding with infrared laser irradiation after clear corneal incision.

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Rasier, Rfat; Ozeren, Mediha; Artunay, Ozgür; Bahçecioğlu, Halil; Seçkin, Ismail; Kalaycoğlu, Hamit; Kurt, Adnan; Sennaroğlu, Alphan; Gülsoy, Murat

2010-09-01

The aim of this study was to investigate the potential of infrared lasers for corneal welding to seal corneal cuts done in an experimental animal model. Full-thickness corneal cuts on freshly enucleated bovine eyes were irradiated with infrared (809-nm diode, 980-nm diode, 1070-nm YLF, and 1980-nm Tm:YAP) lasers to get immediate laser welding. An 809-nm laser was used with the topical application of indocyanine green to enhance the photothermal interaction at the weld site. In total, 60 bovine eyes were used in this study; 40 eyes were used in the first part of the study for the determination of optimal welding parameters (15 eyes were excluded because of macroscopic carbonization, opacification, or corneal shrinkage; 2 eyes were used for control), and 20 eyes were used for further investigation of more promising lasers (YLF and Tm:YAP). Laser wavelength, irradiating power, exposure time, and spot size were the dose parameters, and optimal dose for immediate closure with minimal thermal damage was estimated through histological examination of welded samples. In the first part of the study, results showed that none of the applications was satisfactory. Full-thickness success rates were 28% (2 of 7) for 809-nm and for 980-nm diode lasers and 67% (2 of 3) for 1070-nm YLF and (4 of 6) for 1980-nm Tm:YAP lasers. In the second part of the study, YLF and Tm:YAP lasers were investigated with bigger sample size. Results were not conclusive but promising again. Five corneal incisions were full-thickness welded out of 10 corneas with 1070-nm laser, and 4 corneal incisions were partially welded out of 10 corneas with 1980-nm laser in the second part of the study. Results showed that noteworthy corneal welding could be obtained with 1070-nm YLF laser and 1980-nm Tm:YAP laser wavelengths. Furthermore, in vitro and in vivo studies will shed light on the potential usage of corneal laser welding technique.

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model.

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Gore, Daniel M; O'Brart, David; French, Paul; Dunsby, Chris; Allan, Bruce D

2015-07-01

To measure depth-specific riboflavin concentrations in corneal stroma using two-photon fluorescence microscopy and compare commercially available transepithelial corneal collagen cross-linking (CXL) protocols. Transepithelial CXL riboflavin preparations--MedioCross TE, Ribocross TE, Paracel plus VibeX Xtra, and iontophoresis with Ricrolin+--were applied to the corneal surface of fresh postmortem rabbit eyes in accordance with manufacturers' recommendations for clinical use. Riboflavin 0.1% (VibeX Rapid) was applied after corneal epithelial debridement as a positive control. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35-μm thick were cut on a cryostat, mounted on a slide, and imaged by two-photon fluorescence microscopy. Mean (SD) concentrations were calculated from five globes tested for each protocol. Peak riboflavin concentration of 0.09% (± 0.01) was observed within the most superficial stroma (stromal depth 0-10 μm) in positive controls (epithelium-off). At the same depth, peak stromal riboflavin concentrations for MedioCross TE, Ricrolin+, Paracel/Xtra, and Ribocross TE were 0.054% (± 0.01), 0.031% (0.003), 0.021% (± 0.001), and 0.015% (± 0.004), respectively. At a depth of 300 μm (within the demarcation zone commonly seen after corneal cross-linking), the stromal concentration in epithelium-off positive controls was 0.075% (± 0.006), while at the same depth MedioCross TE and Ricrolin+ achieved 0.018% (± 0.006) and 0.016% (0.002), respectively. None of the remaining transepithelial protocols achieved concentrations above 0.005% at this same 300-μm depth. Overall, MedioCross TE was the best-performing transepithelial formulation. Corneal epithelium is a significant barrier to riboflavin absorption into the stroma. Existing commercial transepithelial CXL protocols achieve relatively low riboflavin concentrations in the anterior corneal stroma when compared to gold standard epithelium-off absorption

Corneal surface temperature change as the mode of stimulation of the non-contact corneal aesthesiometer.

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Murphy, P J; Morgan, P B; Patel, S; Marshall, J

1999-05-01

The non-contact corneal aesthesiometer (NCCA) assesses corneal sensitivity by using a controlled pulse of air, directed at the corneal surface. The purpose of this paper was to investigate whether corneal surface temperature change was a component in the mode of stimulation. Thermocouple experiment: A simple model corneal surface was developed that was composed of a moistened circle of filter paper placed on a thermocouple and mounted on a glass slide. The temperature change produced by different stimulus pressures was measured for five different ambient temperatures. Thermal camera experiment: Using a thermal camera, the corneal surface temperature change was measured in nine young, healthy subjects after exposure to different stimulus air pulses. Pulse duration was set at 0.9 s but was varied in pressure from 0.5 to 3.5 millibars. Thermocouple experiment: An immediate drop in temperature was detected by the thermocouple as soon as the air flow was incident on the filter paper. A greater temperature change was produced by increasing the pressure of the incident air flow. A relationship was found and a calibration curve plotted. Thermal camera experiment: For each subject, a drop in surface temperature was detected at each stimulus pressure. Furthermore, as the stimulus pressure increased, the induced reduction in temperature also increased. A relationship was found and a calibration curve plotted. The NCCA air-pulse stimulus was capable of producing a localized temperature change on the corneal surface. The principal mode of corneal nerve stimulation, by the NCCA air pulse, was the rate of temperature change of the corneal surface.

Denervation of the Lacrimal Gland Leads to Corneal Hypoalgesia in a Novel Rat Model of Aqueous Dry Eye Disease.

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Aicher, Sue A; Hermes, Sam M; Hegarty, Deborah M

2015-10-01

Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production. Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED. Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli. Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.

The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.

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Inna Maltseva

Full Text Available Corneal epithelial wound repair involves the migration of epithelial cells to cover the defect followed by the proliferation of the cells to restore thickness. Heparan sulfate proteoglycans (HSPGs are ubiquitous extracellular molecules that bind to a plethora of growth factors, cytokines, and morphogens and thereby regulate their signaling functions. Ligand binding by HS chains depends on the pattern of four sulfation modifications, one of which is 6-O-sulfation of glucosamine (6OS. SULF1 and SULF2 are highly homologous, extracellular endosulfatases, which post-synthetically edit the sulfation status of HS by removing 6OS from intact chains. The SULFs thereby modulate multiple signaling pathways including the augmentation of Wnt/ß-catenin signaling. We found that wounding of mouse corneal epithelium stimulated SULF1 expression in superficial epithelial cells proximal to the wound edge. Sulf1⁻/⁻, but not Sulf2⁻/⁻, mice, exhibited a marked delay in healing. Furthermore, corneal epithelial cells derived from Sulf1⁻/⁻ mice exhibited a reduced rate of migration in repair of a scratched monolayer compared to wild-type cells. In contrast, human primary corneal epithelial cells expressed SULF2, as did a human corneal epithelial cell line (THCE. Knockdown of SULF2 in THCE cells also slowed migration, which was restored by overexpression of either mouse SULF2 or human SULF1. The interchangeability of the two SULFs establishes their capacity for functional redundancy. Knockdown of SULF2 decreased Wnt/ß-catenin signaling in THCE cells. Extracellular antagonists of Wnt signaling reduced migration of THCE cells. However in SULF2- knockdown cells, these antagonists exerted no further effects on migration, consistent with the SULF functioning as an upstream regulator of Wnt signaling. Further understanding of the mechanistic action of the SULFs in promoting corneal repair may lead to new therapeutic approaches for the treatment of corneal injuries.

Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

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Darci M Fink

Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

Burn mouse models

DEFF Research Database (Denmark)

Calum, Henrik; Høiby, Niels; Moser, Claus

2014-01-01

Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....

Corneal neurotoxicity due to topical benzalkonium chloride.

Science.gov (United States)

Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-04-06

The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001). Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.

Corneal densitometry and its correlation with age, pachymetry, corneal curvature, and refraction.

Science.gov (United States)

Garzón, Nuria; Poyales, Francisco; Illarramendi, Igor; Mendicute, Javier; Jáñez, Óscar; Caro, Pedro; López, Alfredo; Argüeso, Francisco

2017-12-01

To determine normative corneal densitometry values in relation to age, sex, refractive error, corneal thickness, and keratometry, measured using the Oculus Pentacam system. Three hundred and thirty-eight healthy subjects (185 men; 153 women) with no corneal disease underwent an exhaustive ocular examination. Corneal densitometry was expressed in standardized grayscale units (GSU). The mean corneal densitometry over the total area was 16.46 ± 1.85 GSU. The Pearson correlation coefficient for total densitometry was r = 0.542 (p  0.05). This is the first report of normative corneal densitometry values in relation to keratometry, corneal thickness, and spherical equivalent measured with the latest Oculus Pentacam software. Corneal densitometry increases with age, but corneal keratometry and refractive parameters do not affect light scattering in the human cornea.

Turning the tide of corneal blindness

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Matthew S Oliva

2012-01-01

Full Text Available Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world′s largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind.

Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model.

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Khoh-Reiter, Su; Jessen, Bart A

2009-07-28

Benzalkonium chloride (BAC) is a common preservative used in ophthalmic solutions. The aim of this study was to compare the cytotoxic effects of BAC-containing ophthalmic solutions with a BAC-free ophthalmic solution using an organotypic 3-dimensional (3-D) corneal epithelial model and to determine the effects of latanoprost ophthalmic solution and its BAC-containing vehicle on corneal thickness in a monkey model. The cytotoxicity of commercially available BAC-containing ophthalmic formulations of latanoprost (0.02% BAC) and olopatadine (0.01% BAC) was compared to that of BAC-free travoprost and saline in a corneal organotypic 3-D model using incubation times of 10 and 25 minutes. To compare the extent of differentiation of 3-D corneal cultures to monolayer transformed human corneal epithelial (HCE-T) cell cultures, expression levels (mRNA and protein) of the corneal markers epidermal growth factor receptor, transglutaminase 1 and involucrin were quantified. Finally, latanoprost ophthalmic solution or its vehicle was administered at suprapharmacologic doses (two 30 microL drops twice daily in 1 eye for 1 year) in monkey eyes, and corneal pachymetry was performed at baseline and at weeks 4, 13, 26 and 52. In the 3-D corneal epithelial culture assays, there were no significant differences in cytotoxicity between the BAC-containing latanoprost and olopatadine ophthalmic solutions and BAC-free travoprost ophthalmic solution at either the 10- or 25-minute time points. The 3-D cultures expressed higher levels of corneal epithelial markers than the HCE-T monolayers, indicating a greater degree of differentiation. There were no significant differences between the corneal thickness of monkey eyes treated with latanoprost ophthalmic solution or its vehicle (both containing 0.02% BAC) and untreated eyes. The lack of cytotoxicity demonstrated in 3-D corneal cultures and in monkey studies suggests that the levels of BAC contained in ophthalmic solutions are not likely to cause

Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

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Jessen Bart A

2009-07-01

Full Text Available Abstract Background Benzalkonium chloride (BAC is a common preservative used in ophthalmic solutions. The aim of this study was to compare the cytotoxic effects of BAC-containing ophthalmic solutions with a BAC-free ophthalmic solution using an organotypic 3-dimensional (3-D corneal epithelial model and to determine the effects of latanoprost ophthalmic solution and its BAC-containing vehicle on corneal thickness in a monkey model. Methods The cytotoxicity of commercially available BAC-containing ophthalmic formulations of latanoprost (0.02% BAC and olopatadine (0.01% BAC was compared to that of BAC-free travoprost and saline in a corneal organotypic 3-D model using incubation times of 10 and 25 minutes. To compare the extent of differentiation of 3-D corneal cultures to monolayer transformed human corneal epithelial (HCE-T cell cultures, expression levels (mRNA and protein of the corneal markers epidermal growth factor receptor, transglutaminase 1 and involucrin were quantified. Finally, latanoprost ophthalmic solution or its vehicle was administered at suprapharmacologic doses (two 30 μL drops twice daily in 1 eye for 1 year in monkey eyes, and corneal pachymetry was performed at baseline and at weeks 4, 13, 26 and 52. Results In the 3-D corneal epithelial culture assays, there were no significant differences in cytotoxicity between the BAC-containing latanoprost and olopatadine ophthalmic solutions and BAC-free travoprost ophthalmic solution at either the 10- or 25-minute time points. The 3-D cultures expressed higher levels of corneal epithelial markers than the HCE-T monolayers, indicating a greater degree of differentiation. There were no significant differences between the corneal thickness of monkey eyes treated with latanoprost ophthalmic solution or its vehicle (both containing 0.02% BAC and untreated eyes. Conclusion The lack of cytotoxicity demonstrated in 3-D corneal cultures and in monkey studies suggests that the levels of BAC

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

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Chang, Che-Yi; Wang, Ming-Chen; Miyagawa, Takuya; Chen, Zhi-Yu; Lin, Feng-Huei; Chen, Ko-Hua; Liu, Guei-Sheung; Tseng, Ching-Li

2017-01-01

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD) peptide–hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV

Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

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Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

2018-06-01

The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration.

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Lin, Ko-Jo; Loi, Mei-Xue; Lien, Gi-Shih; Cheng, Chieh-Feng; Pao, Hsiang-Yin; Chang, Yun-Chuang; Ji, Andrea Tung-Qian; Ho, Jennifer Hui-Chun

2013-06-14

Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 10(5)) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration

Science.gov (United States)

2013-01-01

Introduction Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Methods Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 105) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Results Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The

Progress of research on corneal collagen cross-linking for corneal melting

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Ke-Ren Xiao

2016-06-01

Full Text Available Corneal collagen cross-linking(CXLcould increase the mechanical strength, biological stability and halt ectasia progression due to covalent bond formed by photochemical reaction between ultraviolet-A and emulsion of riboflavin between collagen fibers in corneal stroma. Corneal melting is an autoimmune related noninfectious corneal ulcer. The mechanism of corneal melting, major treatment, the basic fundamental of ultraviolet-A riboflavin induced CXL and the clinical researches status and experiment in CXL were summarized in the study.

Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium

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Noriaki Nagai

2018-04-01

Full Text Available Sericin is a major constituent of silk produced by silkworms. We previously found that the instillation of sericin enhanced the proliferation of corneal epithelial cells, and acted to promote corneal wound healing in both normal and diabetic model rats. However, the mechanisms by which sericin promotes the proliferation of corneal cells have not been established. In this study, we investigated the effects of sericin on Akt and ERK activation in a human corneal epithelial cell line (HCE-T cells and rat debrided corneal epithelium. Although Akt phosphorylation was not detected following the treatment of HCE-T cells with sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated with sericin was significantly increased, with the cell growth of sericin-treated HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells. On the other hand, both of an ERK inhibitor U0126 (non-specific specific inhibitor and SCH772984 (specific inhibitor attenuated the enhanced cell growth by sericin, and the growth level in the case of co-treatment with sericin and ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor alone. In an in vivo study using rat debrided corneal epithelium, the corneal wound healing rate was enhanced by the instillation of sericin, and this enhancement was also attenuated by the instillation of U0126. In addition, the corneal wound healing rate in rats co-instilled with sericin and U0126 was similar to that following the instillation of U0126 alone. In conclusion, we found that the instillation of sericin enhanced cell proliferation via the activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound healing in rat eyes. These findings provide significant information for designing further studies to develop potent corneal wound-healing drugs.

Preliminary study of rabbit model with corneal neovascularization after thermal burn under the constant temperature

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Yong Jia

2014-07-01

Full Text Available AIM:To explore the suitable conditions in rapid model of corneal neovascularization(CNVafter thermal burn under different constant temperature in rabbit. METHODS: Total 45 New Zealand white rabbits were divided randomly into five groups(A, B, C, D, E. A groups: 100℃(n=10, B groups: 200℃(n=10, C groups: 300℃(n=10, D groups: 400℃(n=10, and E groups: control group(n=5. All left eyes of rabbits in A,B,C,D groups were induced corneal neovascularization by constant temperature burning device. The growth of CNV was observed by slit lamp microscope and the area of CNV were recorded on 4 th, 7 th, 14th, 30th days postoperatively. SPSS 19.0 statistical package was used for data analysis, and the data was recorded by mean±standard deviation. Comparison by analysis of variance was made by repeated measures in the area of neovascularization at each time point in groups. Statistical tests were considered significantly when P values were less than 0.05. RESULTS: On postoperative 4th, 7th, 14th, 30th days: no neovascularization was found after corneal thermal burn in A group, but only a few nebula left(n=2; the area of CNV were(9.16±1.45mm2,(37.73±5.49mm2,(62.44±7.54mm2,(40.28±7.39mm2 in B group respectively; and(11.45±1.04mm2,(44.51±4.64mm2,(66.13±4.13mm2,(43.04±2.33mm2 in C group respectively; and(13.23±0.86mm2,(47.26±4.59mm2,(67.57±4.56mm2,(45.59±4.44mm2 in D group respectively, and part corneal carbide(n=4was observed as well as corneal perforation(n=6were found on 3d in D group. No neovascularization was found in normal control group. Comparison of the areas of CNV at each time point between groups was statistically different, PPCOCLUSION: In 4 to 7d, the higher the temperature is, the more the neovascularization area of CNV are. It has no significant difference in 14 to 30d. But corneal carbide and corneal perforation are often found in 400℃ group, so its modeling failure rate is high. It is between 200℃ and 300℃ that

Intraocular pressure, corneal thickness, and corneal hysteresis in Steinert's myotonic dystrophy

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Carlos Alexandre de A. Garcia Filho

2011-06-01

Full Text Available PURPOSE: Low intraocular pressure (IOP measured by Goldmann applanation tonometry (GAT is one of the ocular manifestations of Steinert's myotonic dystrophy. The goal of this study was to evaluate the corneal-compensated IOP as well as corneal properties (central corneal thickness and corneal hysteresis in patients with myotonic dystrophy. METHODS: A total of 12 eyes of 6 patients with Steinert's myotonic dystrophy (dystrophy group and 12 eyes of 6 age-, race-, and gender-matched healthy volunteers (control group were included in the study. GAT, Dynamic Contour Tonometry (DCT-Pascal and Ocular Response Analyzer (ORA were used to assess the IOP. Central corneal thickness was obtained by ultrasound pachymetry, and corneal hysteresis was analyzed using the ORA device. In light of the multiplicity of tests performed, the significance level was set at 0.01 rather than 0.05. RESULTS: The mean (standard deviation [SD] GAT, DCT, and corneal-compensated ORA IOP in the dystrophy group were 5.4 (1.4 mmHg, 9.7 (1.5 mmHg, and 10.1 (2.6 mmHg, respectively. The mean (SD GAT, DCT, and corneal-compensated ORA IOP in the control group was 12.6 (2.9 mmHg, 15.5 (2.7 mmHg, and 15.8 (3.4 mmHg, respectively. There were significant differences in IOP values between dystrophy and control groups obtained by GAT (mean, -7.2 mmHg; 99% confidence interval [CI], -10.5 to -3.9 mmHg; P<0.001, DCT (mean, -5.9 mmHg; 99% CI, -8.9 to -2.8 mmHg; P<0.001, and corneal-compensated ORA measurements (mean, -5.7 mmHg; 99% CI, -10.4 to -1.0 mmHg; P=0.003. The mean (SD central corneal thickness was similar in the dystrophy (542 [31] µm and control (537 [11] µm groups (P=0.65. The mean (SD corneal hysteresis in the dystrophy and control groups were 11.2 (1.5 mmHg and 9.7 (1.2 mmHg, respectively (P=0.04. CONCLUSIONS: Patients with Steinert's myotonic dystrophy showed lower Goldmann and corneal-compensated IOP in comparison with healthy individuals. Since central corneal thickness and

Optical modeling of a corneal inlay in real eyes to increase depth of focus: optimum centration and residual defocus.

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Tabernero, Juan; Artal, Pablo

2012-02-01

To determine the optimum position to center a small-aperture corneal inlay and the effect of residual defocus in the surgical eye to maximize depth of focus. Laboratorio de Óptica, Universidad de Murcia, Murcia, Spain. Cohort study. Personalized eye models were built using actual data (corneal topography, eye length, ocular aberrations, and eye alignment). A small aperture 1.6 mm in diameter was placed at the corneal plane in each model. The monochromatic and polychromatic Strehl ratios were calculated as a function of the pinhole position. Different residual defocus values were also incorporated into the models, and the through-focus Strehl ratios were calculated. Sixteen eye models were built. For most subjects, the optimum location of the aperture for distance vision was close to the corneal reflex position. For a given optimized centration of the aperture, the best compromise of depth of focus was obtained when the eyes had some residual myopic defocus (range -0.75 to -1.00 diopter [D]). Strehl ratio values were over 0.1 for far distance, which led to visual acuities better than 20/20. The depth of focus was 2.50 D with a mean near visual acuity of Jaeger 1 or better. In eyes with little astigmatism and aberrations, the optimum centration of the small aperture was near the corneal reflex position. To improve optical outcomes with the inlay, some small residual myopia and correction of corneal astigmatism might be required. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Intrastromal corneal ring implants for corneal thinning disorders: an evidence-based analysis.

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2009-01-01

The purpose of this project was to determine the role of corneal implants in the management of corneal thinning disease conditions. An evidence-based review was conducted to determine the safety, effectiveness and durability of corneal implants for the management of corneal thinning disorders. The evolving directions of research in this area were also reviewed. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objectives for corneal implants are to normalize corneal surface topography, improve contact lens tolerability, and restore visual acuity in order to delay or defer the need for corneal transplant. Implant placement is a minimally invasive procedure that is purported to be safe and effective. The procedure is also claimed to be adjustable, reversible, and both eyes can be treated at the same time. Further, implants do not limit the performance of subsequent surgical approaches or interfere with corneal transplant. The evidence for these claims is the focus of this review. The specific research questions for the evidence review were as follows: SafetyCorneal Surface Topographic Effects:Effects on corneal surface remodellingImpact of these changes on subsequent interventions, particularly corneal transplantation (penetrating keratoplasty [PKP])Visual AcuityRefractive OutcomesVISUAL QUALITY (SYMPTOMS): such as contrast vision or decreased visual symptoms (halos, fluctuating vision)Contact lens toleranceFunctional visual rehabilitation and quality of lifePatient satisfaction:Disease Process:Impact on corneal thinning processEffect on delaying or deferring the need for corneal transplantation TARGET POPULATION AND CONDITION Corneal ectasia (thinning) comprises a range of disorders involving either primary disease conditions such as keratoconus and pellucid marginal corneal degeneration or secondary iatrogenic conditions such as corneal thinning occurring after LASIK refractive surgery. The condition occurs when the normally round dome-shaped cornea

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

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Cınar, Yasin; Cingü, Abdullah Kürşat; Sahin, Alparslan; Türkcü, Fatih Mehmet; Yüksel, Harun; Caca, Ihsan

2014-03-01

Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

Novel Vitamin K analogues suppress seizures in zebrafish and mouse models of epilepsy

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Rahn, Jennifer J.; Bestman, Jennifer E.; Josey, Benjamin J.; Inks, Elizabeth S.; Stackley, Krista D.; Rogers, Carolyn E.; Chou, C. James; Chan, Sherine S. L.

2014-01-01

Epilepsy is a debilitating disease affecting 1-2% of the world’s population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit HDACs using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, NQN1, significantly decreased swim activity to levels equal to that of VPA. We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogues. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6 Hz) and corneal kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogues for prevention of seizures and suggest the potential mechanism for this protection may lie in the ability of these compounds to affect energy production. PMID:24291671

Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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Hongshan Liu

Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye.

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Daull, Philippe; Feraille, Laurence; Barabino, Stefano; Cimbolini, Nicolas; Antonelli, Sophie; Mauro, Virgine; Garrigue, Jean-Sébastien

2016-12-01

Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0.1% CsA cationic emulsion, or 1% methylprednisolone (positive control), or non-treated. Aqueous tear production and CFS scores were evaluated at baseline and throughout the treatment period. The lacrimation test confirmed the scopolamine-induced decrease in aqueous production by the lacrimal gland. A reduction of 59% in induced-CFS was observed following topical treatment with 0.1% CsA. The beneficial effect of the cationic emulsion vehicle itself on keratitis was also clearly evidenced by its better performance over 1% methylprednisolone, -36%, vs. -28% on the CFS scores, respectively. This study indicates that the cationic emulsion of CsA (0.1%) was a very effective formulation for the management of corneal epithelium lesions in a severe DED mouse model. In addition, it performed better than a potent glucocorticosteroid (1% methylprednisolone). This cationic emulsion of CsA (0.1%), combining CsA and a tear film oriented therapy (TFOT), i.e. with vehicle properties that mechanically stabilize the tear film, represents a promising new treatment strategy for the management of the signs of dry eye. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hormonal regulation of Na+/K+-dependent ATPase activity and pump function in corneal endothelial cells.

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Hatou, Shin

2011-10-01

Na- and K-dependent ATPase (Na,K-ATPase) in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in these cells. Mouse corneal endothelial cells were exposed to dexamethasone or insulin. ATPase activity was evaluated by spectrophotometric measurement, and pump function was measured using an Ussing chamber. Western blotting and immunocytochemistry were performed to measure the expression of the Na,K-ATPase α1-subunit. Dexamethasone increased Na,K-ATPase activity and the pump function of endothelial cells. Western blot analysis indicated that dexamethasone increased the expression of the Na,K-ATPase α1-subunit but decreased the ratio of active to inactive Na,K-ATPase α1-subunit. Insulin increased Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were transient and blocked by protein kinase C inhibitors and inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A). Western blot analysis indicated that insulin decreased the amount of inactive Na,K-ATPase α1-subunit, but the expression of total Na,K-ATPase α1-subunit was unchanged. Immunocytochemistry showed that insulin increased cell surface expression of the Na,K-ATPase α1-subunit. Our results suggest that dexamethasone and insulin stimulate Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells was mediated by Na,K-ATPase synthesis and an increased enzymatic activity because of dephosphorylation of Na,K-ATPase α1-subunits. The effect of insulin is mediated by the protein kinase C, PP1, and/or PP2A pathways.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

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Dota A

2013-01-01

Full Text Available Atsuyoshi Dota, Yuko Takaoka-Shichijo, Masatsugu NakamuraOphthalmic Research and Development Center, Santen Pharmaceutical Co, Ltd, Ikoma-shi, Nara, JapanPurpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.Keywords: gefarnate, fluorescein staining, rose bengal permeability, rabbit, cat, dry eye

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

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Natalia Vázquez

Full Text Available Corneal keratoplasty (penetrating or lamellar using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis.

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Furusawa, Takaaki; Iwano, Hidetomo; Hiyashimizu, Yutaro; Matsubara, Kazuki; Higuchi, Hidetoshi; Nagahata, Hajime; Niwa, Hidekazu; Katayama, Yoshinari; Kinoshita, Yuta; Hagiwara, Katsuro; Iwasaki, Tomohito; Tanji, Yasunori; Yokota, Hiroshi; Tamura, Yutaka

2016-09-01

Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria, Pseudomonas aeruginosa sometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isolated Myoviridae or Podoviridae phages, which together have a broad host range. They adsorb efficiently to host bacteria; more than 80% of the ΦR18 phage were adsorbed to host cells after 30 s. In our keratitis mouse model, the administration of phage within 3 h also could kill bacteria and suppress keratitis. A phage multiplicity of infection of 100 times the host bacterial number could kill host bacteria effectively. A cocktail of two phages suppressed bacteria in the keratitis model mouse. These data demonstrated that the phages in this study could completely prevent the keratitis caused by P. aeruginosa in a keratitis mouse model. Furthermore, these results suggest that phage may be a more effective prophylaxis for horse keratitis than the current preventive use of antibiotics. Such treatment may reduce the use of antibiotics and therefore antibiotic resistance. Further studies are required to assess phage therapy as a candidate for treatment of horse keratitis. Antibiotic-resistant bacteria are emerging all over the world. Bacteriophages have great potential for resolution of this problem. A bacteriophage, or phage, is a virus that infects bacteria specifically. As a novel therapeutic strategy against racehorse keratitis caused by Pseudomonas aeruginosa, we propose the application of phages for treatment. Phages isolated in this work had in vitro effectiveness for a broad

The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells.

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Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo

2009-05-01

The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase alpha(1)-subunit. Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)-subunit. Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

Effects of subconjunctival administration of anti-high mobility group box 1 on dry eye in a mouse model of Sjӧgren's syndrome.

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Kim, Kyeong Hwan; Kim, Dong Hyun; Jeong, Hyun Jeong; Ryu, Jin Suk; Kim, Yu Jeong; Oh, Joo Youn; Kim, Mee Kum; Wee, Won Ryang

2017-01-01

Extracellular high mobility group box 1 (HMGB1) acts as a damage associated molecular pattern molecule through the Toll-like receptor to promote autoreactive B cell activation, which may be involved in the pathogenesis of Sjӧgren's syndrome. The aim of this study was to investigate the effect of subconjunctival administration of anti-HMGB1 on dry eye in a mouse model of Sjӧgren's syndrome. Ten weeks-old NOD.B10.H2b mice were subconjunctivally injected with 0.02 to 2 μg of anti-HMGB1 antibodies or PBS twice a week for two consecutive weeks. Tear volume and corneal staining scores were measured and compared between before- and after-treatment. Goblet cell density was counted in PAS stained forniceal conjunctiva and inflammatory foci score (>50 cells/focus) was measured in extraorbital glands. Flow cytometry was performed to evaluate the changes in BrdU+ cells, IL-17-, IL-10-, or IFNγ-secreting cells, functional B cells, and IL-22 secreting innate lymphoid cells (ILC3s) in cervical lymph nodes. The level of IL-22 in intraorbital glands was measured by ELISA. Injection of 2 μg or 0.02 μg anti-HMGB1 attenuated corneal epithelial erosions and increased tear secretion (pdry eye. The improvement of dry eye may involve an increase of ILC3s, rather than modulation of B or plasma cells, as shown using a mouse model of Sjӧgren's syndrome.

Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse Cornea

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Baba, Kenkichi; Davidson, Alec J.; Tosini, Gianluca

2015-01-01

Purpose Previous studies have reported the presence of a circadian rhythm in PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina, RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the eye and it is believed to be one of the key circadian signals within the eye. The aim of the present study was to investigate the regulation of the PER2::LUC circadian rhythm in mouse cornea and to determine the role played by MLT. Methods Corneas were obtained from PER2::LUC mice and cultured to measure bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera. To determine the time-dependent resetting of the corneal circadian clocks in response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to the cultured corneas at different times of the day. We also defined the location of the MT2 receptor within different corneal layers using immunohistochemistry. Results A long-lasting bioluminescence rhythm was recorded from cultured PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and endothelium. MLT administration in the early night delayed the cornea rhythm, whereas administration of MLT at late night to early morning advanced the cornea rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent with these results, MT2 immunoreactivity was localized to the corneal epithelium and endothelium. Conclusions Our work demonstrates that MLT entrains the PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea may represent a model to study the molecular mechanisms by which MLT affects the circadian clock. PMID:26207312

Effects of genipin corneal crosslinking in rabbit corneas.

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Avila, Marcel Y; Narvaez, Mauricio; Castañeda, Juan P

2016-07-01

To evaluate the effect of genipin, a natural crosslinking agent, in rabbit eyes. Department of Ophthalmology, Universidad Nacional de Colombia Centro de Tecnologia Oftalmica, Bogotá, Colombia. Experimental study. Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin 1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam). In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas were crosslinked with genipin as described. Corneal curvature, corneal pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp examinations were performed 0, 7, 30, and 60 days after treatment. In the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit corneas with an increase in corneal density and a dose-dependent relationship. Corneal flattening was observed in treated eyes (mean 4.4 diopters ± 0.5 [SD]) compared with the control eyes. Pachymetry and IOP were stable in all evaluations. No eye showed toxicity in the anterior chamber or in the lens. Corneal crosslinking induced by genipin produced significant flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could be useful in the treatment of corneal ectasia and in the modification of corneal curvature. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Equine corneal stromal abscesses

DEFF Research Database (Denmark)

Henriksen, M. D. L.; Andersen, P. H.; Plummer, C. E.

2013-01-01

The last 30 years have seen many changes in the understanding of the pathogenesis and treatment of equine corneal stromal abscesses (SAs). Stromal abscesses were previously considered an eye problem related to corneal bacterial infection, equine recurrent uveitis, corneal microtrauma and corneal....... Medical and surgical treatments are now directed towards elimination of fungal and bacterial infections, reduction and replacement of diseased corneal stroma, and suppression of iridocyclitis. If the abscess and anterior uveitis do not respond satisfactorily to medical therapy, full thickness or split...

NK cells modulate the inflammatory response to corneal epithelial abrasion and thereby support wound healing

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Natural killer cells are lymphocytes of the innate immune system that have crucial cytotoxic and regulatory roles in adaptive immunity and inflammation. Herein, we consider a role for these cells in corneal wound healing. After a 2-mm central epithelial abrasion of the mouse cornea, a subset of clas...

Porcine cadaver iris model for iris heating during corneal surgery with a femtosecond laser

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Sun, Hui; Fan, Zhongwei; Wang, Jiang; Yan, Ying; Juhasz, Tibor; Kurtz, Ron

2015-03-01

Multiple femtosecond lasers have now been cleared for use for ophthalmic surgery, including for creation of corneal flaps in LASIK surgery. Preliminary study indicated that during typical surgical use, laser energy may pass beyond the cornea with potential effects on the iris. As a model for laser exposure of the iris during femtosecond corneal surgery, we simulated the temperature rise in porcine cadaver iris during direct illumination by the femtosecond laser. Additionally, ex-vivo iris heating due to femtosecond laser irradiation was measured with an infrared thermal camera (Fluke corp. Everett, WA) as a validation of the simulation.

Kinetic analysis of the rate of corneal wound healing in Otsuka long-evans Tokushima Fatty rats, a model of type 2 diabetes mellitus.

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Nagai, Noriaki; Murao, Takatoshi; Okamoto, Norio; Ito, Yoshimasa

2010-01-01

Diabetic keratopathy is a well-known ocular complication secondary to type 2 diabetes mellitus. In this study, we performed a kinetic analysis of corneal wound healing in Long-Evans rats (normal rat) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Corneal wound healing in 7-week-old normal rats was mostly complete 24 h after corneal epithelial abrasion, and the process of corneal wound healing took place according to an equation with a first-order rate constant. The rate of corneal wound healing in normal rats decreased with aging. The process of corneal wound healing in 38- and 60-week-old normal and OLETF rats occurred in two phases with rate constants for the first and second phases represented as alpha and beta, respectively. The alpha and beta values in 38- and 60-week-old OLETF rats were lower than those in normal rats of the corresponding age. Furthermore, a close relationship was observed between the corneal wound healing rate constant and plasma glucose levels in OLETF rats. The present studies suggest the sequence of events that occur following damage to the corneal surface in OLETF rats as a model animal for a human type 2 diabetes mellitus.

Diclofenac protects cultured human corneal epithelial cells against hyperosmolarity and ameliorates corneal surface damage in a rat model of dry eye.

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Sawazaki, Ryoichi; Ishihara, Tomoaki; Usui, Shinya; Hayashi, Erika; Tahara, Kayoko; Hoshino, Tatsuya; Higuchi, Akihiro; Nakamura, Shigeru; Tsubota, Kazuo; Mizushima, Tohru

2014-04-21

Dry eye syndrome (DES) is characterized by an increase in tear osmolarity and induction of the expression and nuclear localization of an osmoprotective transcription factor (nuclear factor of activated T-cells 5 [NFAT5]) that plays an important role in providing protection against hyperosmotic tears. In this study, we screened medicines already in clinical use with a view of finding compounds that protect cultured human corneal epithelial cells against hyperosmolarity-induced cell damage. Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and cellular NFAT5 level was measured by immunoblotting. The rat model for DES was developed by removal of the lacrimal glands, with an assessment of corneal surface damage based on levels of fluorescein staining and epithelial apoptosis. Some nonsteroidal anti-inflammatory drugs (NSAIDs), including diclofenac sodium (diclofenac), were identified during the screening procedure. These NSAIDs were able to suppress hyperosmolarity-induced apoptosis and cell growth arrest. In contrast, other NSAIDs, including bromfenac sodium (bromfenac), did not exert such a protective action. Treatment of cells with diclofenac, but not bromfenac, stimulated both the nuclear localization and expression of NFAT5 under hyperosmotic conditions. In the rat model for DES, topical administration of diclofenac (but not bromfenac) to eyes reduced corneal surface damage without affecting the volume of tear fluid. Diclofenac appears to protect cells against hyperosmolarity-induced cell damage and NFAT5 would play an important role in this protective action. The findings reported here may also indicate that the topical administration of diclofenac to eyes may be therapeutically beneficial for DES patients.

Sjögren's syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090.

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Contreras-Ruiz, Laura; Mir, Fayaz A; Turpie, Bruce; Krauss, Achim H; Masli, Sharmila

2016-02-01

Sjögren's syndrome is an autoimmune disease associated with inflammation of exocrine glands with clinical manifestations of dry eye and dry mouth. Dry eye in this disease involves inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an integrin α4 adhesion molecule antagonist in a mouse model of dry eye associated with Sjögren's syndrome. To assess this spontaneously developed ocular surface inflammation related to Sjögren's syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1% dexamethasone or 30 mg/ml GW559090 or vehicle control. Corneal fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1β in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface inflammation was detectable in TSP-1null mice (≥12 wk old), which resulted in increased corneal fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1β as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied dexamethasone and GW559090 significantly reduced corneal fluorescein staining compared to vehicle treatment (p = 0.023 and p syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamic corneal deformation response and integrated corneal tomography

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Marcella Q Salomão

2018-01-01

Full Text Available Measuring corneal biomechanical properties is still challenging. There are several clinical applications for biomechanical measurements, including the detection of mild or early forms of ectatic corneal diseases. This article reviews clinical applications for biomechanical measurements provided by the Corvis ST dynamic non contact tonometer

Development of a human corneal epithelium model utilizing a collagen vitrigel membrane and the changes of its barrier function induced by exposing eye irritant chemicals.

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Takezawa, Toshiaki; Nishikawa, Kazunori; Wang, Pi-Chao

2011-09-01

The brief TEER (trans-epithelial electrical resistance) assay after exposing chemicals to corneal epithelium in vivo is known as a suitable method for evaluating corneal irritancy and permeability quantitatively and continuously. A collagen vitrigel membrane we previously developed is a thin (about 20 μm thick) and transparent membrane composed of high density collagen fibrils equivalent to connective tissues in vivo, e.g. corneal Bowman's membrane. To develop such a TEER assay system in vitro utilizing a human corneal epithelial model, HCE-T cells (a human corneal epithelial cell line) were cultured on the collagen vitrigel membrane substratum prepared in a Millicell chamber suitable for TEER measurement. Human corneal epithelium model possessing 5-6 cell layers sufficient for TEER assay was successfully reconstructed on the substratum in the Millicell chamber by culturing the cells in monolayer for 2 days and subsequently in air-liquid interface for 7 days. The exposure of chemicals to the model induced the time-dependent relative changes of TEER in response to the characteristic of each chemical within a few minutes. These results suggest that the TEER assay using the human corneal epithelial model is very useful for an ocular irritancy evaluation as an alternative to the Draize eye irritation test. Copyright © 2011 Elsevier Ltd. All rights reserved.

Study on phototherapeutic keratotomy for bacterial corneal lesions in rabbit

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Xin Zhou

2018-05-01

Full Text Available AIM: To study the effect of phototherapeutic keratectomy(PTKon rabbit bacterial corneal ulcer model and explore the clinical potential of this method. METHODS: Totally 48 eyes from all the 24 New Zealand rabbits were inoculated with Staphylococcus aureus and bacterial corneal ulcer model was established successfully. At 1d after inoculation, 48 eyes were given levofloxacin eye drops when corneal ulcer was confirmed. Then slit lamp inspection and optical coherence tomography(OCTwere performed to measure the central corneal ulcer depth. All the rabbits right eyes were treated with PTK, as an observation group, left eyes were not treated as a control group. The eye section were observed by slit lamp and central thickness of corneal ulcer was measured by OCT at 3 and 7d after this operation. Rabbits were sacrificed and the cornea was removed for pathological section 7d later. RESULTS: The corneal ulcers in both groups had a tendency to heal, showing a decrease in ulcer area and smoothness of the surface. There was no significant difference in the depth of corneal ulcer between the observation group and the control group before PTK(t=0.706, P=0.484. The difference between the two groups of eyes at 3 and 7d after PTK was obviously(PCONCLUSION: PTK can effectively cure rabbit Staphylococcus aureus corneal ulcer and promote ulcer wound healing, which may be used for clinical treatment of patients with bacterial corneal lesions.

Ocular dimensions, corneal thickness, and corneal curvature in quarter horses with hereditary equine regional dermal asthenia.

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Badial, Peres R; Cisneros-Àlvarez, Luis Emiliano; Brandão, Cláudia Valéria S; Ranzani, José Joaquim T; Tomaz, Mayana A R V; Machado, Vania M; Borges, Alexandre S

2015-09-01

The aim of this study was to compare ocular dimensions, corneal curvature, and corneal thickness between horses affected with hereditary equine regional dermal asthenia (HERDA) and unaffected horses. Five HERDA-affected quarter horses and five healthy control quarter horses were used. Schirmer's tear test, tonometry, and corneal diameter measurements were performed in both eyes of all horses prior to ophthalmologic examinations. Ultrasonic pachymetry was performed to measure the central, temporal, nasal, dorsal, and ventral corneal thicknesses in all horses. B-mode ultrasound scanning was performed on both eyes of each horse to determine the dimensions of the ocular structures and to calculate the corneal curvature. Each corneal region examined in this study was thinner in the affected group compared with the healthy control group. However, significant differences in corneal thickness were only observed for the central and dorsal regions. HERDA-affected horses exhibited significant increases in corneal curvature and corneal diameter compared with unaffected animals. The ophthalmologic examinations revealed mild corneal opacity in one eye of one affected horse and in both eyes of three affected horses. No significant between-group differences were observed for Schirmer's tear test, intraocular pressure, or ocular dimensions. Hereditary equine regional dermal asthenia-affected horses exhibit decreased corneal thickness in several regions of the cornea, increased corneal curvature, increased corneal diameter, and mild corneal opacity. Additional research is required to determine whether the increased corneal curvature significantly impacts the visual accuracy of horses with HERDA. © 2014 American College of Veterinary Ophthalmologists.

Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's syndrome.

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Feeling Y Chen

Full Text Available Sjögren's syndrome (SS is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.

Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's syndrome.

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Chen, Feeling Y; Lee, Albert; Ge, Shaokui; Nathan, Sara; Knox, Sarah M; McNamara, Nancy A

2017-01-01

Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire) gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.

Efficacy of Tectonic Corneal Patch Graft for Progressive Peripheral Corneal Thinning

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Cafer Tanrıverdio

2014-12-01

Full Text Available Objectives: To report the results of tectonic corneal patch graft (TCPG in patients with progressive peripheral corneal thinning (PCT. Materials and Methods: In this study, we included 8 patients who underwent TCPG for PCT or perforated corneal ulceration at Ankara Training and Research Hospital. Results: We performed TCPG in 7 patients for PCT and in 1 patient for perforated corneal ulceration. Mean age was 57.2±16.7 (38- 82 years. Postoperative follow-up time ranged from 6 to 24 months (mean 13.9±6.7. Possible etiologies leading to progressive PCT were trachoma, infectious corneal ulcer, and rheumatoid arthritis-severe dry eye in 2 patients each. Other 2 patients had a progressive PCT following ocular surgery. One of the patients with infectious corneal ulcer also had a trauma caused by a scissor. Amnion membrane transplantation was performed in 3 patients prior to TCPG. While the anatomic success was achieved in all 8 patients, best-corrected visual acuity (BCVA was 0.1 or better in 4 patients (50%. Postoperative BCVA was better than preoperative BCVA in 6 patients (75%. Local peripheral anterior synechiae developed in two eyes. Conclusion: TCPG is a useful therapeutic option in selected cases of corneal thinning and perforations because it effectively restores the integrity of the globe and allows acceptable visual results. (Turk J Ophthalmol 2014; 44: 440-4

Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

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Yuka Okada

Full Text Available In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4 channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT mice are different than those in their TRPV4-null (KO counterpart. Stromal opacification due to fibrosis in KO (n = 128 mice was markedly reduced after 20 days relative to that in WT (n = 157 mice. Immunohistochemistry revealed that increases in polymorphonuclear leukocytes and macrophage infiltration declined in KO mice. Semi-quantitative real time RT-PCR of ocular KO fibroblast cultures identified increases in proinflammatory and monocyte chemoattractant protein-1 chemoattractant gene expression after injury. Biomarker gene expression of fibrosis, collagen1a1 and α-smooth muscle actin were attenuated along with macrophage release of interleukin-6 whereas transforming growth factor β, release was unchanged. Tail vein reciprocal bone marrow transplantation between WT and KO chimera mouse models mice showed that reduced scarring and inflammation in KO mice are due to loss of TRPV4 expression on both corneal resident immune cells, fibroblasts and infiltrating polymorphonuclear leukocytes and macrophages. Intraperitoneal TRPV4 receptor antagonist injection of HC-067047 (10 mg/kg, daily into WT mice reproduced the KO-phenotype. Taken together, alkali-induced TRPV4 activation contributes to inducing fibrosis and inflammation since corneal transparency recovery was markedly improved in KO mice.

Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

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Okada, Yuka; Shirai, Kumi; Miyajima, Masayasu; Reinach, Peter S; Yamanaka, Osamu; Sumioka, Takayoshi; Kokado, Masahide; Tomoyose, Katsuo; Saika, Shizuya

2016-01-01

In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice. Immunohistochemistry revealed that increases in polymorphonuclear leukocytes and macrophage infiltration declined in KO mice. Semi-quantitative real time RT-PCR of ocular KO fibroblast cultures identified increases in proinflammatory and monocyte chemoattractant protein-1 chemoattractant gene expression after injury. Biomarker gene expression of fibrosis, collagen1a1 and α-smooth muscle actin were attenuated along with macrophage release of interleukin-6 whereas transforming growth factor β, release was unchanged. Tail vein reciprocal bone marrow transplantation between WT and KO chimera mouse models mice showed that reduced scarring and inflammation in KO mice are due to loss of TRPV4 expression on both corneal resident immune cells, fibroblasts and infiltrating polymorphonuclear leukocytes and macrophages. Intraperitoneal TRPV4 receptor antagonist injection of HC-067047 (10 mg/kg, daily) into WT mice reproduced the KO-phenotype. Taken together, alkali-induced TRPV4 activation contributes to inducing fibrosis and inflammation since corneal transparency recovery was markedly improved in KO mice.

Corneal Laceration

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Full Text Available ... Tips & Prevention News Ask an Ophthalmologist Patient Stories Español Eye Health / Eye Health A-Z Corneal Laceration ... Laceration Treatment What Is Corneal Laceration? Leer en Español: ¿Qué es una laceración de la córnea? Written ...

Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery.

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Bilgihan, K; Bilgihan, A; Adiguzel, U; Sezer, C; Yis, O; Akyol, G; Hasanreisoglu, B

2002-01-01

Refractive corneal surgery induces keratocyte apoptosis and generates reactive oxygen radicals (ROS) in the cornea. The purpose of the present study is to evaluate the correlation between keratocyte apoptosis and corneal antioxidant enzyme activities after different refractive surgical procedures in rabbits. Rabbits were divided into six groups. All groups were compared with the control group (Group 1), after epithelial scraping (Group 2), epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK: Group 3), transepithelial PRK (Group 4), creation of a corneal flap with microkeratome (Group 5) and laser-assisted in situ keratomileusis (LASIK, Group 6). Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy were used to detect apoptosis in rabbit eyes. Glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities of the corneal tissues were measured with spectrophotometric methods. Corneal Gpx and SOD activities decreased significantly in all groups when compared with the control group (P<0.05) and groups 2, 3 and 6 showed a significantly higher amount of keratocyte apoptosis (P<0.05). Not only a negative correlation was observed between corneal SOD activity and keratocyte apoptosis (cc: -0.3648) but Gpx activity also showed negative correlation with keratocyte apoptosis (cc: -0.3587). The present study illustrates the negative correlation between keratocyte apoptosis and corneal antioxidant enzyme activities. This finding suggests that ROS may be partly responsible for keratocyte apoptosis after refractive surgery.

Extended Release of an Anti–Heparan Sulfate Peptide From a Contact Lens Suppresses Corneal Herpes Simplex Virus-1 Infection

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Jaishankar, Dinesh; Buhrman, Jason S.; Valyi-Nagy, Tibor; Gemeinhart, Richard A.; Shukla, Deepak

2016-01-01

Purpose To prolong the release of a heparan sulfate binding peptide, G2-C, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (HSV-1) infection using in vitro, ex vivo, and in vivo models of corneal HSV-1 infection. Methods Commercially available contact lenses were immersed in peptide solution for 5 days prior to determining the release of the peptide at various time points. Cytotoxicity of the released samples was determined by MTT and cell cycle analysis, and the functional activity of the released samples were assessed by viral entry, and viral spread assay using human corneal epithelial cells (HCE). The ability to suppress infection in human and pig cornea ex vivo and mouse in vivo models were also assessed. Results Peptide G2-C was released through the contact lens. Following release for 3 days, the peptide showed significant activity by inhibiting HSV-1 viral entry and spread in HCE cells. Significant suppression of infection was also observed in the ex vivo and in vivo experiments involving corneas. Conclusions Extended release of an anti–HS peptide through a commercially available contact lens can generate significant anti–HSV-1 activity and provides a new and effective way to control corneal herpes. PMID:26780322

Role of protein kinase C in regulation of Na+- and K +-dependent ATPase activity and pump function in corneal endothelial cells.

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Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Nishida, Teruo

2009-05-01

Na+- and K+-dependent ATPase (Na,K-ATPase) plays an important role in the pump function of the corneal endothelium. We investigated the possible role of protein kinase C (PKC) in regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to phorbol 12,13-dibutyrate (PDBu) to induce activation of PKC. ATPase activity of the cells was evaluated by using ammonium molybdate in spectrophotometric measurement of phosphate released from ATP, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with a Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. PDBu (10(-7) M) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of PDBu were potentiated by the cyclooxygenase inhibitor indomethacin and the cytochrome P(450) inhibitor resorufin and were blocked by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. Our results suggest that PKC bidirectionally regulates Na,K-ATPase activity in mouse corneal endothelial cells: it inhibits Na,K-ATPase activity in a cyclooxygenase- and cytochrome P(450)-dependent manner, whereas it stimulates such activity by activating protein phosphatases 1 or 2A.

Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

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Klein, Brian D; Jacobson, Catherine A; Metcalf, Cameron S; Smith, Misty D; Wilcox, Karen S; Hampson, Aidan J; Kehne, John H

2017-07-01

Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy. Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy. The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models. Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED 50 164 mg/kg), mouse MES (ED 50 83.5 mg/kg) and rat MES (ED 50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED 50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses. The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.

In Vivo Corneal Biomechanical Properties with Corneal Visualization Scheimpflug Technology in Chinese Population

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Ying Wu

2016-01-01

Full Text Available Purpose. To determine the repeatability of recalculated corneal visualization Scheimpflug technology (CorVis ST parameters and to study the variation of biomechanical properties and their association with demographic and ocular characteristics. Methods. A total of 783 healthy subjects were included in this study. Comprehensive ophthalmological examinations were conducted. The repeatability of the recalculated biomechanical parameters with 90 subjects was assessed by the coefficient of variation (CV and intraclass correlation coefficient (ICC. Univariate and multivariate linear regression models were used to identify demographic and ocular factors. Results. The repeatability of the central corneal thickness (CCT, deformation amplitude (DA, and first/second applanation time (A1/A2-time exhibited excellent repeatability (CV% ≤ 3.312% and ICC ≥ 0.929 for all measurements. The velocity in/out (Vin/out, highest concavity- (HC- radius, peak distance (PD, and DA showed a normal distribution. Univariate linear regression showed a statistically significant correlation between Vin, Vout, DA, PD, and HC-radius and IOP, CCT, and corneal volume, respectively. Multivariate analysis showed that IOP and CCT were negatively correlated with Vin, DA, and PD, while there was a positive correlation between Vout and HC-radius. Conclusion. The ICCs of the recalculated parameters, CCT, DA, A1-time, and A2-time, exhibited excellent repeatability. IOP, CCT, and corneal volume significantly influenced the biomechanical properties of the eye.

Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy

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Riazuddin, S. Amer; Parker, David S.; McGlumphy, Elyse J.; Oh, Edwin C.; Iliff, Benjamin W.; Schmedt, Thore; Jurkunas, Ula; Schleif, Robert; Katsanis, Nicholas; Gottsch, John D.

2012-01-01

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes. PMID:22341973

Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival

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Zhaochuan Liu; Haotian Lin; Chulong Huang; Wan Chen; Wu Xiang; Yu Geng; Weirong Chen

2015-01-01

Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution...

Differentiation and molecular profiling of human embryonic stem cell-derived corneal epithelial cells.

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Brzeszczynska, J; Samuel, K; Greenhough, S; Ramaesh, K; Dhillon, B; Hay, D C; Ross, J A

2014-06-01

It has been suggested that the isolation of scalable populations of limbal stem cells may lead to radical changes in ocular therapy. In particular, the derivation and transplantation of corneal stem cells from these populations may result in therapies providing clinical normality of the diseased or damaged cornea. Although feasible in theory, the lack of donor material in sufficient quantity and quality currently limits such a strategy. A potential scalable source of corneal cells could be derived from pluripotent stem cells (PSCs). We developed an in vitro and serum-free corneal differentiation model which displays significant promise. Our stepwise differentiation model was designed with reference to development and gave rise to cells which displayed similarities to epithelial progenitor cells which can be specified to cells displaying a corneal epithelial phenotype. We believe our approach is novel, provides a robust model of human development and in the future, may facilitate the generation of corneal epithelial cells that are suitable for clinical use. Additionally, we demonstrate that following continued cell culture, stem cell-derived corneal epithelial cells undergo transdifferentiation and exhibit squamous metaplasia and therefore, also offer an in vitro model of disease.

Clinical applications of corneal confocal microscopy

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Mitra Tavakoli

2008-06-01

Full Text Available Mitra Tavakoli1, Parwez Hossain2, Rayaz A Malik11Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; 2University of Southampton, Southampton Eye Unit, Southampton General Hospital, Southampton, UKAbstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy, and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.Keywords: corneal confocal microscopy, cornea, infective keratitis, corneal dystrophy, neuropathy

Neurotrophic corneal and conjunctival xerosis

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Svetlana Gennadyevna Zhurova

2014-03-01

Full Text Available Purpose: to develop a method of surgical treatment of patients with corneal ulcers of xerotic etiology and evaluate its efficacy in different time periods after operation. Materials and methods: 68 patients (86 eyes with severe dry eye syndrome complicated by xerotic corneal ulcers were examined. In all patients, the ulcer defect was covered with conjunctiva and amniotic membrane. The operation was combined with an outer tarsorrhaphy and temporary blepharorraphy. Results: All 86 eyes (100% achieved total closure of the ulcer defect, sealing of any perforation and maintaining of corneal transparency beyond the ulcer defect. Conclusion: Surgical closure of corneal ulcers with conjunctiva is an effective method of treatment of xerotic corneal ulcers. It could be recommended in patients with corneal perforation and tendency of descemetocele formation.

Triptolide Suppresses Alkali Burn-Induced Corneal Angiogenesis Along with a Downregulation of VEGFA and VEGFC Expression.

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Wang, Geng; Li, Na; Lv, Xiaohong; Ahmed, Naila; Li, Xinlei; Liu, Huidong; Ma, Jing; Zhang, Yafang

2017-07-01

Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti-inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical-induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration, and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real-time PCR and Western blot were used to determine the expression of vascular endothelial growth factor A (VEGFA) and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn-induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose-dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn-induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. Anat Rec, 300:1348-1355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

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Chang Rae Rho

Full Text Available Granulocyte-macrophage colony-stimulating factor (GM-CSF is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs. We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF. An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml. MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

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Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

2017-11-01

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Human tears reveal insights into corneal neovascularization.

Science.gov (United States)

Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

2012-01-01

Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

Corneal markers of diabetic neuropathy.

Science.gov (United States)

Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Mouse Models of Gastric Cancer

Science.gov (United States)

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

Topical thrombin-related corneal calcification.

Science.gov (United States)

Kiratli, Hayyam; Irkeç, Murat; Alaçal, Sibel; Söylemezoğlu, Figen

2006-09-01

To report a highly unusual case of corneal calcification after brief intraoperative use of topical thrombin. A 44-year-old man underwent sclerouvectomy for ciliochoroidal leiomyoma, during which 35 UNIH/mL lyophilized bovine thrombin mixed with 9 mL of diluent containing 1500 mmol/mL calcium chloride was used. From the first postoperative day, corneal and anterior lenticular capsule calcifications developed, and corneal involvement slightly enlarged thereafter. A year later, 2 corneal punch biopsies confirmed calcification mainly in the Bowman layer. Topical treatment with 1.5% ethylenediaminetetraacetic acid significantly restored corneal clarity. Six months later, a standard extracapsular cataract extraction with intraocular lens placement improved visual acuity to 20/60. This case suggests that topical thrombin drops with elevated calcium concentrations may cause acute corneal calcification in Bowman layer and on the anterior lens capsule.

Influence of eye biometrics and corneal micro-structure on noncontact tonometry.

Directory of Open Access Journals (Sweden)

Danilo A Jesus

Full Text Available Tonometry is widely used as the main screening tool supporting glaucoma diagnosis. Still, its accuracy could be improved if full knowledge about the variation of the corneal biomechanical properties was available. In this study, Optical Coherence Tomography (OCT speckle statistics are used to infer the organisation of the corneal micro-structure and hence, to analyse its influence on intraocular pressure (IOP measurements.Fifty-six subjects were recruited for this prospective study. Macro and micro-structural corneal parameters as well as subject age were considered. Macro-structural analysis included the parameters that are associated with the ocular anatomy, such as central corneal thickness (CCT, corneal radius, axial length, anterior chamber depth and white-to-white corneal diameter. Micro-structural parameters which included OCT speckle statistics were related to the internal organisation of the corneal tissue and its physiological changes during lifetime. The corneal speckle obtained from OCT was modelled with the Generalised Gamma (GG distribution that is characterised with a scale parameter and two shape parameters.In macro-structure analysis, only CCT showed a statistically significant correlation with IOP (R2 = 0.25, p<0.001. The scale parameter and the ratio of the shape parameters of GG distribution showed statistically significant correlation with IOP (R2 = 0.19, p<0.001 and R2 = 0.17, p<0.001, respectively. For the studied group, a weak, although significant correlation was found between age and IOP (R2 = 0.053, p = 0.04. Forward stepwise regression showed that CCT and the scale parameter of the Generalised Gamma distribution can be combined in a regression model (R2 = 0.39, p<0.001 to study the role of the corneal structure on IOP.We show, for the first time, that corneal micro-structure influences the IOP measurements obtained from noncontact tonometry. OCT speckle statistics can be employed to learn about the corneal micro

Influence of eye biometrics and corneal micro-structure on noncontact tonometry.

Science.gov (United States)

Jesus, Danilo A; Majewska, Małgorzata; Krzyżanowska-Berkowska, Patrycja; Iskander, D Robert

2017-01-01

Tonometry is widely used as the main screening tool supporting glaucoma diagnosis. Still, its accuracy could be improved if full knowledge about the variation of the corneal biomechanical properties was available. In this study, Optical Coherence Tomography (OCT) speckle statistics are used to infer the organisation of the corneal micro-structure and hence, to analyse its influence on intraocular pressure (IOP) measurements. Fifty-six subjects were recruited for this prospective study. Macro and micro-structural corneal parameters as well as subject age were considered. Macro-structural analysis included the parameters that are associated with the ocular anatomy, such as central corneal thickness (CCT), corneal radius, axial length, anterior chamber depth and white-to-white corneal diameter. Micro-structural parameters which included OCT speckle statistics were related to the internal organisation of the corneal tissue and its physiological changes during lifetime. The corneal speckle obtained from OCT was modelled with the Generalised Gamma (GG) distribution that is characterised with a scale parameter and two shape parameters. In macro-structure analysis, only CCT showed a statistically significant correlation with IOP (R2 = 0.25, p<0.001). The scale parameter and the ratio of the shape parameters of GG distribution showed statistically significant correlation with IOP (R2 = 0.19, p<0.001 and R2 = 0.17, p<0.001, respectively). For the studied group, a weak, although significant correlation was found between age and IOP (R2 = 0.053, p = 0.04). Forward stepwise regression showed that CCT and the scale parameter of the Generalised Gamma distribution can be combined in a regression model (R2 = 0.39, p<0.001) to study the role of the corneal structure on IOP. We show, for the first time, that corneal micro-structure influences the IOP measurements obtained from noncontact tonometry. OCT speckle statistics can be employed to learn about the corneal micro-structure and

Corneal Transplantation

DEFF Research Database (Denmark)

Hjortdal, Jesper Østergaard

with less risk of rejection episodes. Besides covering updated chapters on penetrating keratoplasty, and anterior and posterior lamellar procedures, this textbook also gives a thorough overview of the history of corneal transplantation and a detailed presentation of the microstructural components...... and to assist fellows and corneal surgeons in their advice and selection of patients for the best surgical procedure considering benefi ts and risks....

Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals

OpenAIRE

Akihiro Higuchi; Hiroyoshi Inoue; Yoshio Kaneko; Erina Oonishi; Kazuo Tsubota

2016-01-01

The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy ...

Applications of corneal topography and tomography: a review.

Science.gov (United States)

Fan, Rachel; Chan, Tommy Cy; Prakash, Gaurav; Jhanji, Vishal

2018-03-01

Corneal imaging is essential for diagnosing and management of a wide variety of ocular diseases. Corneal topography is used to characterize the shape of the cornea, specifically, the anterior surface of the cornea. Most corneal topographical systems are based on Placido disc that analyse rings that are reflected off the corneal surface. The posterior corneal surface cannot be characterized using Placido disc technology. Imaging of the posterior corneal surface is useful for diagnosis of corneal ectasia. Unlike corneal topographers, tomographers generate a three-dimensional recreation of the anterior segment and provide information about the corneal thickness. Scheimpflug imaging is one of the most commonly used techniques for corneal tomography. The cross-sectional images generated by a rotating Scheimpflug camera are used to locate the anterior and posterior corneal surfaces. The clinical uses of corneal topography include, diagnosis of corneal ectasia, assessment of corneal astigmatism, and refractive surgery planning. This review will discuss the applications of corneal topography and tomography in clinical practice. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Dynamic Corneal Surface Mapping with Electronic Speckle Pattern Interferometry

Science.gov (United States)

Iqbal, S.; Gualini, M. M. S.

2013-06-01

In view of the fast advancement in ophthalmic technology and corneal surgery, there is a strong need for the comprehensive mapping and characterization techniques for corneal surface. Optical methods with precision non-contact approaches have been found to be very useful for such bio measurements. Along with the normal mapping approaches, elasticity of corneal surface has an important role in its characterization and needs to be appropriately measured or estimated for broader diagnostics and better prospective surgical results, as it has important role in the post-op corneal surface reconstruction process. Use of normal corneal topographic devices is insufficient for any intricate analysis since these devices operate at relatively moderate resolution. In the given experiment, Pulsed Electronic Speckle Pattern Interferometry has been utilized along with an excitation mechanism to measure the dynamic response of the sample cornea. A Pulsed ESPI device has been chosen for the study because of its micron-level resolution and other advantages in real-time deformation analysis. A bovine cornea has been used as a sample in the subject experiment. The dynamic response has been taken on a chart recorder and it is observed that it does show a marked deformation at a specific excitation frequency, which may be taken as a characteristic elasticity parameter for the surface of that corneal sample. It was seen that outside resonance conditions the bovine cornea was not that much deformed. Through this study, the resonance frequency and the corresponding corneal deformations are mapped and plotted in real time. In these experiments, data was acquired and processed by FRAMES plus computer analysis system. With some analysis of the results, this technique can help us to refine a more detailed corneal surface mathematical model and some preliminary work was done on this. Such modelling enhancements may be useful for finer ablative surgery planning. After further experimentation

Effects of artificial tear treatment on corneal epithelial thickness and corneal topography findings in dry eye patients.

Science.gov (United States)

Çakır, B; Doğan, E; Çelik, E; Babashli, T; Uçak, T; Alagöz, G

2018-05-01

To investigate the effects of artificial tear treatment on central corneal epithelial thickness, and central, mid-peripheral and peripheral corneal thicknesses in patients with dry eye disease (DED). Patients with DED underwent ocular examinations, including Schirmer-2 test, slit lamp examination for tear break-up time (BUT), corneal topography (CT) for measuring mean central, mid-peripheral and peripheral corneal thickness values and anterior segment optic coherence tomography (AS-OCT) for obtaining central corneal epithelial thickness. After artificial tear treatment (carboxymethylcellulose and sodium hyaluronate formulations) for one month, patients were examined again at a second visit and the results were compared. Sixty-one eyes of 33 female dry eye patients (mean age: 38.3±5.7 years) were enrolled. The mean follow-up time was 36.4±3.3 days. The mean tear BUT and Schirmer-1 tests revealed significant improvement after treatment (P=0.000, P=0.000, respectively). Central corneal epithelium and mean mid-peripheral corneal thicknesses measured significantly higher after treatment (P=0.001, P=0.02). Changes in central and peripheral corneal thicknesses were not statistically significant. Artificial tear treatment in dry eye patients seems to increase central corneal epithelial and mid-peripheral corneal thicknesses. Measurement of corneal epithelial thickness can be a useful tool for evaluation of treatment response in dry eye patients. Further long-term prospective studies are needed to investigate this item. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Topical Drug Formulations for Prolonged Corneal Anesthesia

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Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

Evaluation of intraocular pressure according to corneal thickness before and after excimer laser corneal ablation for myopia.

Science.gov (United States)

Hamed-Azzam, Shirin; Briscoe, Daniel; Tomkins, Oren; Shehedeh-Mashor, Raneen; Garzozi, Hanna

2013-08-01

Intraocular pressure is affected by corneal thickness and biomechanics. Following ablative corneal refractive surgery, corneal structural changes occur. The purpose of the study is to determine the relationship between the mean central corneal thickness (CCT) and the change in intraocular pressure measurements following various corneal ablation techniques, using different measurement methods. Two hundred myopic eyes undergoing laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) were enrolled into a prospective, non-randomized study. Corneal parameters examined included full ocular examination, measurement of CCT, corneal topography, corneal curvature and ocular refractivity. Intraocular pressure measurements were obtained using three different instruments-non-contact tonometer, Goldmann applanation tonometer and TonoPen XL (TonoPen-Central and TonoPen-Peripheral). All measurements were performed pre-operatively and 4 months post-operatively. Post-operative intraocular pressure was significantly lower than pre-operative values, with all instruments (p value tonometer and non-contact tonometer (p value < 0.001, ANOVA). Intraocular pressure readings are significantly reduced following corneal ablation surgery. We determined in our myopic patient cohort that the TonoPen XL intraocular pressure measurement method is the least affected following PRK and LASIK as compared to other techniques.

CONTACT LENS RELATED CORNEAL ULCER

Directory of Open Access Journals (Sweden)

AGARWAL P

2010-01-01

Full Text Available A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are:overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. The presenting symptoms of contact lens related corneal ulcers include eye discomfort, foreign body sensation and lacrimation. More serious symptoms are redness (especially circum-corneal injection, severe pain, photophobia, eye discharge and blurring of vision. The diagnosis is established by a thorough slit lamp microscopic examination with fluorescein staining and corneal scraping for Gram stain and culture of the infective organism. Delay in diagnosing and treatment can cause permanent blindness, therefore an early referral to ophthalmologist and commencing of antimicrobial therapy can prevent visual loss.

Exponential Decay Metrics of Topical Tetracaine Hydrochloride Administration Describe Corneal Anesthesia Properties Mechanistically.

Science.gov (United States)

Ethington, Jason; Goldmeier, David; Gaynes, Bruce I

2017-03-01

To identify pharmacodynamic (PD) and pharmacokinetic (PK) metrics that aid in mechanistic understanding of dosage considerations for prolonged corneal anesthesia. A rabbit model using 0.5% tetracaine hydrochloride was used to induce corneal anesthesia in conjunction with Cochet-Bonnet anesthesiometry. Metrics were derived describing PD-PK parameters of the time-dependent domain of recovery in corneal sensitivity. Curve fitting used a 1-phase exponential dissociation paradigm assuming a 1-compartment PK model. Derivation of metrics including half-life and mean ligand residence time, tau (τ), was predicted by nonlinear regression. Bioavailability was determined by area under the curve of the dose-response relationship with varying drop volumes. Maximal corneal anesthesia maintained a plateau with a recovery inflection at the approximate time of predicted corneal drug half-life. PDs of recovery of corneal anesthesia were consistent with a first-order drug elimination rate. The mean ligand residence time (tau, τ) was 41.7 minutes, and half-life was 28.89 minutes. The mean estimated corneal elimination rate constant (ke) was 0.02402 minute. Duration of corneal anesthesia ranged from 55 to 58 minutes. There was no difference in time domain PD area under the curve between drop volumes. Use of a small drop volume of a topical anesthetic (as low as 11 μL) is bioequivalent to conventional drop size and seems to optimize dosing regiments with a little effect on ke. Prolongation of corneal anesthesia may therefore be best achieved with administration of small drop volumes at time intervals corresponding to the half-life of drug decay from the corneal compartment.

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

Directory of Open Access Journals (Sweden)

Chang CY

2016-12-01

Full Text Available Che-Yi Chang,1,2,* Ming-Chen Wang,2,* Takuya Miyagawa,1 Zhi-Yu Chen,1 Feng-Huei Lin,3,4 Ko-Hua Chen,5,6 Guei-Sheung Liu,7 Ching-Li Tseng1 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, 4Institute of Biomedical Engineering, National Taiwan University, 5Department of Ophthalmology, Taipei Veterans General Hospital, 6Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia *These authors contributed equally to this work Abstract: Neovascularization (NV of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG, presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD peptide–hyaluronic acid (HA-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV, with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a

Correlations between corneal and total wavefront aberrations

Science.gov (United States)

Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

2002-06-01

Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

[Current quality management situation and administration countermeasure study of enterprises marketing corneal contact lens].

Science.gov (United States)

Liu, Yungui; Yao, Ying; Shangguan, Shihao; Gu, Qun; Gao, Wuming; Chen, Yaoshui

2014-05-01

Study the current quality management situation of enterprises marketing corneal contact lens via systemic investigations and explore effective administration countermeasures in the future. The quality management indicators of sixty-two corneal contact lens marketing enterprises in Xuhui district of Shanghai were systematically investigated and enterprises of different operation models was compared and analyzed. Wholesale enterprises and retail chain enterprises are apparently better than independent enterprises almost in all facets. Facilitate market accession of corneal contact lens marketing enterprises, encourage the business model of retail chain, enhance supervision of corneal contact lens marketing enterprises, especially independent franchisors.

Corneal Toxicity Following Exposure to Asclepias Tuberosa.

Science.gov (United States)

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa . Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa , whose latex contains cardenolides that inhibit the Na + / K + -ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa . Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity.

Distrofia corneal de Schnyder

Directory of Open Access Journals (Sweden)

Michel Guerra Almaguer

Full Text Available La principal entidad hereditaria con depósitos de lípidos en el estroma corneal es la distrofia cristalina central, conocida como distrofia de Schnyder, quien la describió en Suiza en 1927. Se caracteriza por depósitos blanco-amarillentos en el estroma corneal central y superficial. Se presenta un paciente de 28 años, del sexo masculino y piel negra, con antecedente de salud anterior. Acudió a consulta y refirió una disminución de la visión y cambio de coloración progresiva de ambos ojos, de años de evolución. En la exploración oftalmológica de ambos ojos se apreciaron lesiones blanquecinas anulares a nivel del estroma corneal, con ligera turbidez corneal central. Los estudios refractivos realizados constataron un astigmatismo hipermetrópico simple. El resto del examen oftalmológico fue negativo. Para el diagnóstico de certeza se empleó el microscopio confocal. Se concluye que el caso presenta una distrofia corneal estromal de tipo cristalina, de Schnyder.

Anterior corneal profile with variable asphericity.

Science.gov (United States)

Rosales, Marco A; Juárez-Aubry, Montserrat; López-Olazagasti, Estela; Ibarra, Jorge; Tepichín, Eduardo

2009-12-10

We present a corneal profile in which the eccentricity, e(Q=-e(2)), has a nonlinear continuous variation from the center outwards. This nonlinear variation is intended to fit and reproduce our current experimental data in which the anterior corneal surface of the human eye exhibits different values of e at different diameters. According to our clinical data, the variation is similar to an exponential decay. We propose a linear combination of two exponential functions to describe the variation of e. We then calculate the corneal sagittal height by substituting e in the first-order aspherical surface equation to obtain the corneal profile. This corneal profile will be used as a reference to analyze the resultant profiles of the customized corneal ablation in refractive surgery.

Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-jun N-terminal kinase 2 (JNK2) pathway.

Science.gov (United States)

Pelegrino, F S A; Pflugfelder, S C; De Paiva, C S

2012-01-01

Patients with tear dysfunction often experience increased irritation symptoms when subjected to drafty and/or low humidity environmental conditions. The purpose of this study was to investigate the effects of low humidity stress (LHS) on corneal barrier function and expression of cornified envelope (CE) precursor proteins in the epithelium of C57BL/6 and c-jun N-terminal kinase 2 (JNK2) knockout (KO) mice. LHS was induced in both strains by exposure to an air draft for 15 (LHS15D) or 30 days (LHS30D) at a relative humidity LHS15D showed corneal barrier dysfunction, decreased apical corneal epithelial cell area, higher MMP-9 expression and gelatinase activity and increased involucrin and SPRR-2 immunoreactivity in the corneal epithelium compared to NS mice. JNK2KO mice were resistant to LHS-induced corneal barrier disruption. MMP-3,-9,-13, IL-1α, IL-1β, involucrin and SPRR-2a RNA transcripts were significantly increased in C57BL/6 mice at LHS15D, while no change was noted in JNK2KO mice. LHS is capable of altering corneal barrier function, promoting pathologic alteration of the TJ complex and stimulating production of CE proteins by the corneal epithelium. Activation of the JNK2 signaling pathway contributes to corneal epithelial barrier disruption in LHS. Copyright © 2011 Elsevier Ltd. All rights reserved.

History of corneal transplantation in Australia.

Science.gov (United States)

Coster, Douglas J

2015-04-01

Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Glaucoma after corneal replacement.

Science.gov (United States)

Baltaziak, Monika; Chew, Hall F; Podbielski, Dominik W; Ahmed, Iqbal Ike K

Glaucoma is a well-known complication after corneal transplantation surgery. Traditional corneal transplantation surgery, specifically penetrating keratoplasty, has been slowly replaced by the advent of new corneal transplantation procedures: primarily lamellar keratoplasties. There has also been an emergence of keratoprosthesis implants for eyes that are high risk of failure with penetrating keratoplasty. Consequently, there are different rates of glaucoma, pathogenesis, and potential treatment in the form of medical, laser, or surgical therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of the horizontal corneal diameter, central corneal thickness, and axial length in premature infants

Directory of Open Access Journals (Sweden)

Ozdemir Ozdemir

2014-08-01

Full Text Available Purpose: To determine the horizontal corneal diameter, central corneal thickness, and axial length in premature infants. Methods: Infants with a birth weight of less than 2,500 g or with a gestation period of less than 36 weeks were included in the study. Infants with retinopathy of prematurity (ROP were allocated to Group 1 (n=138, while those without ROP were allocated to Group 2 (n=236. All infants underwent a complete ophthalmologic examination, including corneal diameter measurements, pachymetry, biometry, and fundoscopy. Between-group comparisons of horizontal corneal diameter, central corneal thickness, and axial lengths were performed. Independent sample t-tests were used for statistical analysis. Results: Data was obtained from 374 eyes of 187 infants (102 female, 85 male. The mean gestational age at birth was 30.7 ± 2.7 weeks (range 25-36 weeks, the mean birth weight was 1,514 ± 533.3 g (range 750-1,970 g, and the mean postmenstrual age at examination was 40.0 ± 4.8 weeks. The mean gestational age and the mean birth weight of Group 1 were statistically lower than Group 2 (p0.05. Conclusions: The presence of ROP in premature infants does not alter the horizontal corneal diameter, central corneal thickness, or axial length.

Corneal Toxicity Following Exposure to Asclepias Tuberosa

DEFF Research Database (Denmark)

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas

2017-01-01

PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small...... epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. RESULTS: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides...... that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity...

Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Keratoconus Eyes after Accelerated Corneal Collagen Crosslinking

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David P. Piñero

2017-01-01

Full Text Available Purpose. To analyze the errors associated to corneal power calculation using the keratometric approach in keratoconus eyes after accelerated corneal collagen crosslinking (CXL surgery and to obtain a model for the estimation of an adjusted corneal refractive index nkadj minimizing such errors. Methods. Potential differences (ΔPc among keratometric (Pk and Gaussian corneal power (PcGauss were simulated. Three algorithms based on the use of nkadj for the estimation of an adjusted keratometric corneal power (Pkadj were developed. The agreement between Pk1.3375 (keratometric power using the keratometric index of 1.3375, PcGauss, and Pkadj was evaluated. The validity of the algorithm developed was investigated in 21 keratoconus eyes undergoing accelerated CXL. Results. Pk1.3375 overestimated corneal power between 0.3 and 3.2 D in theoretical simulations and between 0.8 and 2.9 D in the clinical study (ΔPc. Three linear equations were defined for nkadj to be used for different ranges of r1c. In the clinical study, differences between Pkadj and PcGauss did not exceed ±0.8 D nk=1.3375. No statistically significant differences were found between Pkadj and PcGauss (p>0.05 and Pk1.3375 and Pkadj (p<0.001. Conclusions. The use of the keratometric approach in keratoconus eyes after accelerated CXL can lead to significant clinical errors. These errors can be minimized with an adjusted keratometric approach.

Melatonin receptors: latest insights from mouse models

Science.gov (United States)

Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

2014-01-01

Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

Human corneal epithelial subpopulations

DEFF Research Database (Denmark)

Søndergaard, Chris Bath

2013-01-01

Corneal epithelium is being regenerated throughout life by limbal epithelial stem cells (LESCs) believed to be located in histologically defined stem cell niches in corneal limbus. Defective or dysfunctional LESCs result in limbal stem cell deficiency (LSCD) causing pain and decreased visual acuity...... subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum...

Corneal collagen crosslinking and pigment dispersion syndrome.

Science.gov (United States)

LaHood, Benjamin R; Moore, Sacha

2017-03-01

We describe the case of a keratoconus patient with pigment dispersion syndrome (PDS) who was treated for progressive corneal ectasia with corneal collagen crosslinking (CXL). Pigment dispersion syndrome has been shown to have associated morphologic changes of the corneal endothelium. Corneal CXL has the potential to cause toxicity to the corneal endothelium, and adjacent pigment might increase the likelihood of damage. In this case, the presence of PDS had no detrimental effect on the outcome of treatment, and no complications were observed at 12 months follow-up, indicating that it may be safe to perform corneal CXL in the setting of PDS. This is an important observation as the number of indications for corneal CXL grows. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report

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Mehmet Balcı

2015-08-01

Full Text Available ABSTRACTWe report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignant melanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignant melanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C improved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition.

Healed corneal ulcer with keloid formation.

Science.gov (United States)

Alkatan, Hind M; Al-Arfaj, Khalid M; Hantera, Mohammed; Al-Kharashi, Soliman

2012-04-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman's layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a corneal keloid which was supported by further ultrastructural study. The corneal graft remained clear 6 months after surgery and the patient was satisfied with the visual outcome. Penetrating keratoplasty may be an effective surgical option for corneal keloids in young adult patients.

Current status of accelerated corneal cross-linking

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Michael Mrochen

2013-01-01

Full Text Available Corneal cross-linking with riboflavin is a technique to stabilize or reduce corneal ectasia, in diseases such as keratoconus and post-laser-assisted in situ keratomileusis (LASIK ectasia. There is an interest by patient as well as clinicians to reduce the overall treatment time. Especially, the introduction of corneal cross-linking in combination with corneal laser surgery demands a shorter treatment time to assure a sufficient patient flow. The principles and techniques of accelerated corneal cross-linking is discussed.

Corneal Regeneration After Photorefractive Keratectomy: A Review

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Javier Tomás-Juan

2015-07-01

Full Text Available Photorefractive keratectomy (PRK remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain.

Evaluation of subbasal nerve morphology and corneal sensation after accelerated corneal collagen cross-linking treatment on keratoconus.

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Ozgurhan, Engin Bilge; Celik, Ugur; Bozkurt, Ercument; Demirok, Ahmet

2015-05-01

The aim of this study was to report on the evaluation of corneal nerve fiber density and corneal sensation after accelerated corneal collagen cross-linking on keratoconus patients. The study was performed on 30 keratoconus eyes (30 participants: 16 M, 14 F; 17-32 years old) treated with accelerated collagen cross-linking for disease stabilization. Mean outcome measures were corneal sensation evaluation by Cochet-Bonnet esthesiometry and subbasal nerve fiber density assessment by corneal in vivo confocal microscopy. All corneal measurements were performed using scanning slit confocal microscopy (ConfoScan 4, Nidek Technologies, Padova, Italy). The accelerated corneal collagen cross-linking procedure was performed on 30 eyes of 30 patients (19 right, 63.3%; 11 left, 27.7%). The mean age was 23.93 ± 4. The preoperative mean keratometry, apex keratometry and pachymetry values were 47.19 ± 2.82 D, 56.79 ± 5.39 and 426.1 ± 25.6 μm, respectively. Preoperative mean corneal sensation was 56.3 ± 5.4 mm (with a range from 40 to 60 mm), it was significantly decreased at 1st and 3rd month visit and increased to preoperative values after 6th month visit. Preoperative mean of subbasal nerve fiber density measurements was 22.8 ± 9.7 nerve fiber/mm(2) (with a range of 5-45 mm), it was not still at the preoperative values at 6th month (p = 0.0001), however reached to the preoperative values at 12th month (p = 0.914). Subbasal nerve fibers could reach the preoperative values at the 12th month after accelerated corneal collagen cross-linking treatment although the corneal sensation was improved at 6th month. These findings imply that the subjective healing process is faster than the objective evaluation of the keratoconus patients' cornea treated with accelerated corneal collagen cross-linking.

Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves.

Science.gov (United States)

Cruzat, Andrea; Hamrah, Pedram; Cavalcanti, Bernardo M; Zheng, Lixin; Colby, Kathryn; Pavan-Langston, Deborah

2016-05-01

To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 μm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time.

Lineage tracing in the adult mouse corneal epithelium supports the limbal epithelial stem cell hypothesis with intermittent periods of stem cell quiescence

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Natalie J. Dorà

2015-11-01

Full Text Available The limbal epithelial stem cell (LESC hypothesis proposes that LESCs in the corneal limbus maintain the corneal epithelium both during normal homeostasis and wound repair. The alternative corneal epithelial stem cell (CESC hypothesis proposes that LESCs are only involved in wound repair and CESCs in the corneal epithelium itself maintain the corneal epithelium during normal homeostasis. We used tamoxifen-inducible, CreER-loxP lineage tracing to distinguish between these hypotheses. Clones of labelled cells were induced in adult CAGG-CreER;R26R-LacZ reporter mice and their distributions analysed after different chase periods. Short-lived clones, derived from labelled transient amplifying cells, were shed during the chase period and long-lived clones, derived from stem cells, expanded. At 6 weeks, labelled clones appeared at the periphery, extended centripetally as radial stripes and a few reached the centre by 14 weeks. Stripe numbers depended on the age of tamoxifen treatment. Stripes varied in length, some were discontinuous, few reached the centre and almost half had one end at the limbus. Similar stripes extended across the cornea in CAGG-CreER;R26R-mT/mG reporter mice. The distributions of labelled clones are inconsistent with the CESC hypothesis and support the LESC hypothesis if LESCs cycle between phases of activity and quiescence, each lasting several weeks.

Corneal Regeneration After Photorefractive Keratectomy: A Review.

Science.gov (United States)

Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

2015-01-01

Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Partial Denervation of Subbasal Axons Persists Following Debridement Wounds to the Mouse Cornea

Science.gov (United States)

Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M.; Saban, Daniel R.; Stepp, Mary Ann

2015-01-01

Although sensory reinnervation occurs after injury in the PNS, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify subbasal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of subbasal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7d after superficial trephination, subbasal axon density returns to control levels; by 28d the vortex reforms. Although axon density is similar to control 14d after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14d, axons retract from the center leaving the subbasal axon density reduced by 37.2% and 36.8% at 28d after dulled blade and rotating burr wounding, respectively, compared to control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration associated genes (RAGs) involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7d after injury and by 14d and 28d after wounding, many of these basal cells undergo apoptosis and die. While subbasal axons are restored to their normal density and morphology after superficial trephination, subbasal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14d

Rational Design of Mouse Models for Cancer Research

NARCIS (Netherlands)

Landgraf, M.; McGovern, J.A.; Friedl, P.; Hutmacher, D.W.

2018-01-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models.

Corneal laceration caused by river crab

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Vinuthinee N

2015-01-01

Full Text Available Naidu Vinuthinee,1,2 Anuar Azreen-Redzal,1 Jaafar Juanarita,1 Embong Zunaina2 1Department of Ophthalmology, Hospital Sultanah Bahiyah, Alor Setar, 2Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Abstract: A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. Keywords: corneal ulcer, pediatric trauma, ocular injury

Visual outcome after corneal transplantation for corneal perforation and iris prolapse in 37 horses

DEFF Research Database (Denmark)

Henriksen, Michala de Linde; Plummer, C. E.; Mangan, B.

2012-01-01

We wanted to investigate the visual outcome of horses presented with iris prolapse and treated with corneal transplantation.......We wanted to investigate the visual outcome of horses presented with iris prolapse and treated with corneal transplantation....

Corneal iron ring after conductive keratoplasty.

Science.gov (United States)

Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Pallikaris, Ioannis G

2003-08-01

To report formation of corneal iron ring deposits after conductive keratoplasty. Observational case report. Case report. A 54-year-old woman underwent conductive keratoplasty for hyperopia. One year after conductive keratoplasty, iron ring pattern pigmentation was detected at the corneal epithelium of both eyes. This is the first report of the appearance of corneal iron ring deposits following conductive keratoplasty treatment in a patient. It is suggested that alterations in tear film stability, resulting from conductive keratoplasty-induced changes in corneal curvature, constitute the contributory factor for these deposits.

Explore the full thick layer of corneal transplantation in the treatment of pseudomonas aeruginosa corneal ulcer infection

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Xin Wang

2015-02-01

Full Text Available AIM: To explore the feasibility, safety and effect of the full-thickness lamellar keratoplasty for the treatment of pseudomonas aeruginosa corneal ulcer. METHODS: Based on a retrospective non-controlled study, 25 patients were given the full-thickness lamellar keratoplasty for clinical diagnosis of pseudomonas aeruginosa infection and corneal ulcer medication conventional anti-gram-negative bacteria. Routine follow-up were carried out at postoperative 1wk; 1, 3, 6, 12, 18mo to observe the situation of corneal epithelial healing, recurrent infection, immune rejection, graft transparency and best corrected visual acuity, etc. At the 6 and 12mo postoperative, corneal endothelial cell density was reexamined.RESULTS: No patients because of Descemet's membrane rupture underwent penetrating keratoplasty surgery: One only in cases of bacterial infection after 1mo, once again did not cultivate a culture of bacteria pseudomonas aeruginosa, and the remaining 24 cases average follow-up 14±6mo, corneal graft were transparent, the cure rate was 96%. At the sixth month after surgery, there were 16 cases of eye surgery best corrected visual acuity ≥4.5, of which 3 cases ≥4.8. At the sixth month after surgery, the average corneal endothelial cell density 2 425±278/mm2; At 12mo postoperatively, it was 2 257± 326/mm2.CONCLUSION: Full-thickness lamellar keratoplasty is an effective method of pseudomonas aeruginosa infection in the treatment of corneal ulcers, corneal drying material glycerol can be achieved by visual effects.

Contact Lens Related Corneal Ulcer

OpenAIRE

Loh, KY; Agarwal, P

2010-01-01

A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are: overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. Th...

A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I

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Daniel C Mendez

Full Text Available Mucopolysaccharidosis type I (MPS I is an inherited α-L-iduronidase (IDUA, I deficiency in which glycosaminoglycan (GAG accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches.

Riboflavin for corneal cross-linking.

Science.gov (United States)

O'Brart, D P S

2016-06-01

Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) radiation is the first therapeutic modality that appears to arrest the progression of keratoconus and other corneal ectasias. Riboflavin is central to the process, acting as a photosensitizer for the production of oxygen singlets and riboflavin triplets. These free radicals drive the CXL process within the proteins of the corneal stroma, altering its biomechanical properties. Riboflavin also absorbs the majority of the UVA radiation, which is potentially cytotoxic and mutagenic, within the anterior stroma, preventing damage to internal ocular structures, such as the corneal endothelium, lens and retina. Clinical studies report cessation of ectatic progression in over 90% of cases and the majority document significant improvements in visual, keratometric and topographic parameters. Clinical follow-up is limited to 5-10 years, but suggests sustained stability and enhancement in corneal shape. Sight-threatening complications are rare. The optimal stromal riboflavin dosage for CXL is as yet undetermined. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

Mouse models of Fanconi anemia

International Nuclear Information System (INIS)

Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J.

2009-01-01

Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

Mouse models of Fanconi anemia

Energy Technology Data Exchange (ETDEWEB)

Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: niedernhoferl@upmc.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)

2009-07-31

Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

Corneal topography measurements for biometric applications

Science.gov (United States)

Lewis, Nathan D.

The term biometrics is used to describe the process of analyzing biological and behavioral traits that are unique to an individual in order to confirm or determine his or her identity. Many biometric modalities are currently being researched and implemented including, fingerprints, hand and facial geometry, iris recognition, vein structure recognition, gait, voice recognition, etc... This project explores the possibility of using corneal topography measurements as a trait for biometric identification. Two new corneal topographers were developed for this study. The first was designed to function as an operator-free device that will allow a user to approach the device and have his or her corneal topography measured. Human subject topography data were collected with this device and compared to measurements made with the commercially available Keratron Piccolo topographer (Optikon, Rome, Italy). A third topographer that departs from the standard Placido disk technology allows for arbitrary pattern illumination through the use of LCD monitors. This topographer was built and tested to be used in future research studies. Topography data was collected from 59 subjects and modeled using Zernike polynomials, which provide for a simple method of compressing topography data and comparing one topographical measurement with a database for biometric identification. The data were analyzed to determine the biometric error rates associated with corneal topography measurements. Reasonably accurate results, between three to eight percent simultaneous false match and false non-match rates, were achieved.

Successful transplantation of in vitro expanded human corneal endothelial precursors to corneal endothelial surface using a nanocomposite sheet

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Parikumar P

2011-01-01

Full Text Available Background: Though the transplantation of in vitro expanded human corneal endothelial precursors in animal models of endothelial damage by injecting into the anterior chamber has been reported, the practical difficulties of accomplishing such procedure in human patients have been a hurdle to clinical translation. Here we report the successful transplantation of in vitro expanded human corneal precursor cells to an animal eye using a transparent Nano-composite sheet and their engraftment.Materials and Methods: Human Corneal endothelial cells (HCEC were isolated from human cadaver eyes with informed consent and expanded in the lab using a sphere forming assay in a novel Thermoreversible Gelation Polymer (TGP for 26 days. HCEC obtained by sphere forming assay were seeded in a novel Nano-composite sheet, which was made of PNIPA-NC gels by in-situ, free-radical polymerization of NIPA monomer in the presence of exfoliated clay (synthetic hectorite “Laponite XLG” uniformly dispersed in aqueous media. After a further seven days in vitro culture of HCEC in the Nano-composite sheet, cells were harvested and transplanted on cadaver-bovine eyes (n=3. The cells were injected between the corneal endothelial layer and the Nano-composite sheet that had been placed prior to the injection in close proximity to the endothelial layer. After three hours, the transplanted Nano-composite sheets were removed from the bovine eyes and subjected to microscopic examination. The corneas were subjected to Histo-pathological studies along with controls. Results: HCEC formed sphere like colonies in TGP which expressed relevant markers as confirmed by RT-PCR. Microscopic studies of the Nanosheets and histopathological studies of the cornea of the Bull’s eye revealed that the HCEC got engrafted to the corneal endothelial layer of the bovine eyes with no remnant cells in the Nanosheet. Conclusion: Transplantation of in vitro expanded donor human corneal endothelial cells

Chlorpromazine-induced corneal endothelial phototoxicity

International Nuclear Information System (INIS)

Hull, D.S.; Csukas, S.; Green, K.

1982-01-01

Chlorpromazine, which has been used extensively for the treatment of psychiatric disorders, is known to accumulate in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Specular microscopic perfusion of corneal endothelial cells in darkness with 0.5 mM chlorpromazine HCl resulted in a swelling rate of 18 +/- 2 micrometer/hr, whereas corneas exposed to long-wavelength ultraviolet light for 3 min in the presence of 0.5 mM chlorpromazine swelled at 37 +/- 9 micrometer/hr (p less than 0.01). Preirradiation of 0.5 mM chlorpromazine solution with ultraviolet light for 30 min and subsequent corneal perfusion with the solution resulted in a corneal swelling rate of 45 +/- 19 micrometer/hr. Cornea endothelial cells perfused with 0.5 mM chlorpromazine that was preirradiated with ultraviolet light showed marked swelling on scanning electron microscopic examination, whereas those perfused with nonirradiated chlorpromazine were flat and showed a normal mosaic pattern. Combining either 500 U/ml catalase or 290 U/ml superoxide dismutase with chlorpromazine did not alter photoinduction of corneal swelling. The data suggest that corneal endothelial chlorpromazine phototoxicity is secondary to cytotoxic products resulting from the photodynamically induced decomposition of chlorpromazine and is not caused by hydrogen peroxide or superoxide anion generated during the phototoxic reaction

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

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Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-01-01

Topical application of benzalkonium chloride (BAK) to the eye causes dose-related corneal neurotoxicity. Corneal inflammation and reduction in aqueous tear production accompany neurotoxicity. Cessation of BAK treatment leads to recovery of corneal nerve density.

Role of insulin in regulation of Na+-/K+-dependent ATPase activity and pump function in corneal endothelial cells.

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Hatou, Shin; Yamada, Masakazu; Akune, Yoko; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo; Tsubota, Kazuo

2010-08-01

The Na(+)-/K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells was investigated. Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na,K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na,K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na,K-ATPase alpha(1)-subunit. Insulin increased the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na,K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na,K-ATPase alpha(1)-subunit. These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.

A mouse dry eye model induced by topical administration of the air pollutant particulate matter 10.

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Li, Juan; Tan, Gang; Ding, Xiaoyan; Wang, Yahong; Wu, Anhua; Yang, Qichen; Ye, Lei; Shao, Yi

2017-12-01

To introduce a novel dry eye mouse model induced by topical administration of the air pollutant particulate matter 10 (PM 10 ). A total of 60 male BALB/c mice were used in this study and divided into two groups: group A (PBS eye drops, n=30) and group B (PM 10 eye drop group, n=30). Each treatment was dosed four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14 consecutive days in the right eye. The clinical manifestations of dry eye were measured before therapy and 4, 7 and 14days post-treatment respectively, which included the tear volume, tear break-up (BUT) time, corneal fluorescein staining, rose bengal staining, Lissamine Green staining and inflammatory index. Eye samples were collected on D14 and examined by histologic light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-α (TNF-α), NF-κB-p65 and NF-κB Western Blot analysis. At 0d, 7d and 14d, there were no statistical changes in tear volume, BUT after treatment (P>0.05) with PBS in group A. In group B, all items showed statistical differences at each time point (Plevels of K10 and reduced number of goblet cells in the conjunctival fornix in group B. PM 10 significantly increased the levels of TNF-α, NF-κB-p65 and NF-κB in the cornea. PM 10 can damage the tear film function and cause the destruction of the structural organization of ocular surface in mice. Topical administration of PM 10 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of DES. Copyright © 2017. Published by Elsevier Masson SAS.

Long-term outcomes of wedge resection at the limbus for high irregular corneal astigmatism after repaired corneal laceration

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Jun Du

2016-06-01

Full Text Available AIM: To evaluate the clinical value of wedge resection at corneal limbus in patients with traumatic corneal scarring and high irregular astigmatism. METHODS: Patients with traumatic corneal astigmatism received wedge resection at least 6mo after suture removal from corneal wound. The uncorrected distance visual acuities (UCVA and best corrected distance visual acuities (BCVA, pre- and post-operation astigmatism, spherical equivalent (SE, safety and complications were evaluated. RESULTS: Ten eyes (10 patients were enrolled in this study. Mean follow-up time after wedge resection was 37.8±15.4mo (range, 20-61mo. The mean UCVA improved from +1.07±0.55 logMAR to +0.43±0.22 logMAR (P=0.000 and the mean BCVA from +0.50±0.30 logMAR to +0.15±0.17 logMAR (P=0.000. The mean astigmatism power measured by retinoscopy was -2.03±2.27 D postoperatively and -2.83±4.52 D preoperatively (P=0.310. The mean SE was -0.74±1.61 D postoperatively and -0.64±1.89 D preoperatively (P=0.601. Two cases developed mild pannus near the sutures. No corneal perforation, infectious keratitis or wound gape occurred. CONCLUSION: Corneal-scleral limbal wedge resection with compression suture is a safe, effective treatment for poor patients with high irregular corneal astigmatism after corneal-scleral penetrating injury. Retinoscopy can prove particularly useful for high irregular corneal astigmatism when other measurements are not amenable.

Corneal Deformation Response and Ocular Geometry: A Noninvasive Diagnostic Strategy in Marfan Syndrome.

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Beene, Lauren C; Traboulsi, Elias I; Seven, Ibrahim; Ford, Matthew R; Sinha Roy, Abhijit; Butler, Robert S; Dupps, William J

2016-01-01

To evaluate corneal air-puff deformation responses and ocular geometry as predictors of Marfan syndrome. Prospective observational clinical study. Sixteen investigator-derived, 4 standard Ocular Response Analyzer (ORA), and geometric variables from corneal tomography and optical biometry using Oculus Pentacam and IOL Master were assessed for discriminative value in Marfan syndrome, measuring right eyes of 24 control and 13 Marfan syndrome subjects. Area under the receiver operating characteristic (AUROC) curve was assessed in univariate and multivariate analyses. Six investigator-derived ORA variables successfully discriminated Marfan syndrome. The best lone disease predictor was Concavity Min (Marfan syndrome 47.5 ± 20, control 69 ± 14, P = .003; AUROC = 0.80). Corneal hysteresis (CH) and corneal resistance factor (CRF) were decreased (Marfan syndrome CH 9.45 ± 1.62, control CH 11.24 ± 1.21, P = .01; Marfan syndrome CRF 9.77 ± 1.65, control CRF 11.03 ± 1.72, P = .01) and corneas were flatter in Marfan syndrome (Marfan syndrome Kmean 41.25 ± 2.09 diopter, control Kmean 42.70 ± 1.81 diopter, P = .046). No significant differences were observed in central corneal thickness, axial eye length, or intraocular pressure. A multivariate regression model incorporating corneal curvature and hysteresis loop area (HLA) provided the best predictive value for Marfan syndrome (AUROC = 0.85). This study describes novel biodynamic features of corneal deformation responses in Marfan syndrome, including increased deformation, decreased bending resistance, and decreased energy dissipation capacity. A predictive model incorporating HLA and corneal curvature shows greatest potential for noninvasive clinical diagnosis of Marfan syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Induction of corneal collagen cross-linking in experimental corneal alkali burns in rabbits

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Marcello Colombo-Barboza

2014-10-01

Full Text Available Objective: To evaluate the effect of riboflavin-ultraviolet-A-induced cross-linking (CXL following corneal alkali burns in rabbits. Methods: The right corneas and limbi of ten rabbits were burned using a 1N solution of NaOH and the animals were then divided into two groups: a control group submitted to clinical treatment alone and an experimental group that was treated 1 h after injury with CXL, followed by the same clinical treatment as administered to the controls. Clinical parameters were evaluated post-injury at 1, 7, 15, and 30 days by two independent observers. Following this evaluation, the corneas were excised and examined histologically. Results: There were no statistically significant differences in clinical parameters, such as hyperemia, corneal edema, ciliary injection, limbal ischemia, secretion, corneal neovascularization, symblepharon, or blepharospasm, at any of the time-points evaluated. However, the size of the epithelial defect was significantly smaller in the CXL group (p<0.05 (day 15: p=0.008 and day 30: p=0.008 and the extent of the corneal injury (opacity lesion was also smaller (day 30: p=0.021. Histopathology showed the presence of collagen bridges linking the collagen fibers in only the CXL group. Conclusions: These results suggest that the use of CXL may improve the prognosis of acute corneal alkali burns.

Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

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Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

2015-11-01

Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal

Corneal Toxicity Following Exposure to Asclepias Tuberosa

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Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; G?l, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

PURPOSE: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa.METHODS: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine.RESULTS: The corneal ...

Corneal hydrops induced by Bell’s paralysis in a case of corneal ectasia

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Lokman Aslan

2017-09-01

Full Text Available An 18-year-old male patient presented with suddenly decreased vision, itching, corneal edema and an inability to close the left eye. They had left Bell’s paralysis for two weeks and had used high diopter glasses for five years. The best corrected visual acuity was 0.4 in their right eye and counting fingers in the left eye. Biomicroscopic examination revealed thinning and steepening of the cornea in the right eye and anterior protrusion of the cornea, stromal edema and punctate disruption of the epithelium in the left eye. Topographic image of the right eye was consistent with keratoconus. Six months later, stromal edema gradually regressed and a corneal scar ensued. This case presentation emphasizes that Bell’s palsy may induce disease progression in a patient with preexisting corneal ectasia and results in corneal hydrops. [Arch Clin Exp Surg 2017; 6(3.000: 165-167

New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

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Koizumi, Noriko; Okumura, Naoki; Ueno, Morio; Kinoshita, Shigeru

2014-11-01

Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

Resolvin E1 (RX-10001) reduces corneal epithelial barrier disruption and protects against goblet cell loss in a murine model of dry eye.

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de Paiva, Cintia S; Schwartz, C Eric; Gjörstrup, Per; Pflugfelder, Stephen C

2012-11-01

Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye. C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid-Schiff reagent. RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1. RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.

Late onset corneal ectasia after LASIK surgery.

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Said, Ashraf; Hamade, Issam H; Tabbara, Khalid F

2011-07-01

To report late onset corneal ectasia following myopic LASIK. A retrospective cohort case series. Nineteen patients with late onset corneal ectasia following LASIK procedure were examined at The Eye Center, Riyadh, Saudi Arabia. Patients underwent LASIK for myopia with spherical equivalent ranging from -1.4 to -13.75 diopters. Age and gender, history of systemic or local diseases, and time of onset of corneal ectasia were recorded. Eye examination and corneal topographical analyses were done before and after LASIK surgery. Nineteen patients (29 eyes) with late onset corneal ectasia were identified from 1998 to 2008 in 13 male and six female patients. The mean follow-up period was 108 ± 23 months (range 72-144 months). No patient had pre-operative identifiable risk factors for corneal ectasia and the mean time of onset was 57 ± 24 months (range 24-120 months after LASIK). The pre-operative values included mean central pachymetry 553 ± 25 μm, mean keratometry reading of 42.9 ± 1.5 diopters, average oblique cylinder of 1.4 ± 1.2 diopters, posterior surface elevation of 26 ± 2.1 diopters, corneal flap thickness of 160 μm, mean spherical equivalent of -5.6 ± 3.6 diopters, and calculated residual corneal stromal bed thickness was 288 ± 35 μm. Three (5 eyes) patients developed ectasia after pregnancy. Three (4 eyes) patients developed corneal ectasia following severe adenoviral keratoconjunctivitis and had positive PCR for adenovirus type 8. Corneal ectasia may develop many years after LASIK surgery and symptoms could go undetected for some time. Pregnancy and adenoviral keratoconjunctivitis occurred post-operatively in six patients.

Designing Hydrogel Adhesives for Corneal Wound Repair

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Grinstaff, Mark W.

2013-01-01

Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers – single molecular weight, highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reactions to couple the individual dendrimers together to from the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant. PMID:17889330

Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

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Møller, H U

1989-12-01

This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

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Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane.

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Rohaina, Che Man; Then, Kong Yong; Ng, Angela Min Hwei; Wan Abdul Halim, Wan Haslina; Zahidin, Aida Zairani Mohd; Saim, Aminuddin; Idrus, Ruszymah B H

2014-03-01

The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model. Copyright © 2014 Mosby, Inc. All rights reserved.

A new nanosecond UV laser at 355 nm: early results of corneal flap cutting in a rabbit model.

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Trost, Andrea; Schrödl, Falk; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Kaser-Eichberger, Alexandra; Krefft, Karolina; Vogel, Alfred; Linz, Norbert; Freidank, Sebastian; Hilpert, Andrea; Zimmermann, Inge; Grabner, Günther; Reitsamer, Herbert A

2013-12-03

A new 355 nm UV laser was used for corneal flap cutting in an animal model and tested for clinical and morphologic alterations. Corneal flaps were created (Chinchilla Bastards; n = 25) with an UV nanosecond laser at 355 nm (150 kHz, pulse duration 850 ps, spot-size 1 μm, spot spacing 6 × 6 μm, side cut Δz 1 μm; cutting depth 130 μm) and pulse energies of 2.2 or 2.5 μJ, respectively. Following slit-lamp examination, animals were killed at 6, 12, and 24 hours after treatment. Corneas were prepared for histology (hematoxylin and eosin [HE], TUNEL-assay) and evaluated statistically, followed by ultrastructural investigations. Laser treatment was tolerated well, flap lift was easier at 2.5 μJ compared with 2.2 μJ. Standard HE at 24 hours revealed intact epithelium in the horizontal cut, with similar increase in corneal thickness at both energies. Irrespective of energy levels, TUNEL assay revealed comparable numbers of apoptotic cells in the horizontal and vertical cut at 6, 12, and 24 hours, becoming detectable in the horizontal cut as an acellular stromal band at 24 hours. Ultrastructural analysis revealed regular morphology in the epi- and endothelium, while in the stroma, disorganized collagen lamellae were detectable representing the horizontal cut, again irrespective of energy levels applied. This new UV laser revealed no epi- nor endothelial damage at energies feasible for corneal flap cutting. Observed corneal swelling was lower compared with existing UV laser studies, albeit total energy applied here was much higher. Observed loss of stromal keratinocytes is comparable with available laser systems. Therefore, this new laser is suitable for refractive surgery, awaiting its test in a chronic environment.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

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Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

Progress in corneal wound healing

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Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

2015-01-01

Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and

Preliminary study of the correlation between refractive error and corneal refractive power, corneal asphericity in myopic eye

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Qi-Chao Han

2014-05-01

Full Text Available AIM: To investigate the correlation between myopic refractive error and relative factors, including the corneal refractive power, posterior refractive power, axial length, corneal asphericity coefficient Q value, central cornea thickness(CCTand intraocular pressure(IOP. METHODS:According to the degree of myopia measured by subjective refraction, 138 myopia patients were divided into three subgroups: mild group(-1.00D--3.00D, moderate group(-3.25D--6.00D, high group(>6.00D. The Pentacam anterior segment tomographer(Germany, Oculus Companywas used to measure the corneal refractive power, posterior refractive power, and corneal asphericity in the right eye. IOP, CCT and axial length were measured by a non-contact tonometer and A-scan ultrasonic, respectively. The data was analyzed with a Pearson correlation analysis and one-way ANOVA. RESULTS: The myopic refractive error was negatively correlated with the axial length(r=-0.682, Pr=0.009, P=0.925. The axial length was negatively correlated with corneal refractive power(r=-0.554, Pr=0.674, Pr=-0.375, P=0.01. There was no significantly correlation between the myopic refractive error and CCT, IOP(r=-0.138, P=0.141; r=-0.121, P=0.157. CONCLUSION:The corneal refractive power plays the role of emmetropization during the development of myopia. There is clinic significance for the correlation between Q value and refractive error, IOP to guide the corneal refractive surgery.

The wobbler mouse, an ALS animal model

DEFF Research Database (Denmark)

Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

2013-01-01

This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

Central corneal thickness and related factors in an elderly American Chinese population.

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Wang, Dandan; Singh, Kuldev; Weinreb, Robert; Kempen, John; He, Mingguang; Lin, Shan

2011-07-01

To assess central corneal thickness and related factors in an elderly American Chinese population residing in San Francisco. Cross-sectional community based study. American Chinese aged 40 years and older were enrolled using random cluster sampling and volunteer screening in the Chinatown district of San Francisco. The following data were obtained: central corneal thickness by ultrasound pachymetry, intraocular pressure by Goldmann applanation tonometry, axial length by A-scan biometry, refractive status and corneal curvature by autorefractor. History of systemic and ocular diseases was collected via standard questionnaire. Central corneal thickness. Of 311 eligible subjects, 274 consented to study participation, and 228 phakic eyes were analyzed. Mean corneal thickness was 524.1 ± 31.1 µm, 545.5 ± 30.9 µm and 538.9 ± 31.8 µm in the sampling cluster, volunteer group and all subjects, respectively. A multiple linear regression model showed corneal thickness to be negatively associated with age (standardized regression coefficient [SRC] = -0.21; P = 0.016) and corneal curvature (SRC = -0.19; P = 0.018) but positively correlated with intraocular pressure (SRC = 0.20; P = 0.023). The distribution of central corneal thickness among this American Chinese population is similar to that reported in studies from East Asia. The independent factors associated with thinner corneas included older age, lower intraocular pressure and greater corneal curvature. While descendents of Chinese immigrants in America have, on average, thicker corneas than their ancestors, this phenomenon is potentially impacted by the level of intraocular pressure. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Inhibition of erythropoietin siRNA on corneal neovascularization of rabbit

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Yu-Shun Xue

2017-03-01

Full Text Available AIM: To observe the expression of erythropoietin(EPOon the corneal of rabbit and evaluate the inhibition effect of EPO siRNA on corneal neovascularization(CNV. METHODS: Totally 22 healthy rabbits were randomly divided into 2 groups, which were experimental group and normal control group. Both eyes of rabbits in experimental group were chosen to establish corneal neovascularization model by alkali burn. The morphologic change of corneal was observed with slit lamp microscope and the area of CNV was calculated every day. After alkali burn, the right eye of the experimental group was accepted EPO siRNA injection under the conjunctiva, and the left eye was assigned to be experimental control group. The corneal with CNV was collected for immunohistochemistry at 3d, 7d, 14d, 21d after alkali burn, and the expression of EPO was measured. RESULTS: CNV began growing at the 3d after alkali burn in experimental group, and it was vigorous growing at 7d-14d period. The result of immunohistochemistry shows that the expression of EPO increased after the operation. Compared with experimental group, the rabbits who were treated by EPO siRNA was found with less neovascularization on their corneal, and the expression of EPO decreased. There were statistical significance between the two group at different time(PCONCLUSION: EPO is likely to play an important role on CNV growth, and EPO siRNA can inhibit the growth of CNV by restraining the expression of EPO.

Application of Novel Drugs for Corneal Cell Regeneration

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Sang Beom Han

2018-01-01

Full Text Available Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

Corneal Deformation Response and Ocular Geometry: A Non-invasive Diagnostic Strategy in Marfan Syndrome

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Beene, Lauren C.; Traboulsi, Elias I.; Seven, Ibrahim; Ford, Matthew R.; Roy, Abhijit Sinha; Butler, Robert S.; Dupps, William J.

2015-01-01

Purpose To evaluate corneal air-puff deformation responses and ocular geometry as predictors of Marfan syndrome. Design Prospective observational clinical study Methods Sixteen investigator-derived, 4 standard Ocular Response Analyzer (ORA), and geometric variables from corneal tomography and optical biometry using Oculus Pentacam and IOL Master were assessed for discriminative value in Marfan syndrome, measuring right eyes of 24 control and 13 Marfan syndrome subjects. Area under the receiver operating characteristic (AUROC) curve was assessed in univariate and multivariate analyses Results Six investigator-derived ORA variables successfully discriminated Marfan syndrome. The best lone disease predictor was Concavity Min (Marfan syndrome 47.5 ± 20, control 69 ± 14, p = 0.003; AUROC = 0.80). Corneal hysteresis and corneal resistance factor were decreased (Marfan syndrome CH 9.45 ± 1.62, control CH 11.24 ± 1.21, p = 0.01; Marfan syndrome CRF 9.77 ± 1.65, control CRF 11.03 ± 1.72, p = 0.01) and corneas were flatter in Marfan syndrome (Marfan syndrome Kmean 41.25 ± 2.09 D, control Kmean 42.70 ± 1.81 D, p = 0.046). No significant differences were observed in central corneal thickness, axial eye length, or intraocular pressure. A multivariate regression model incorporating corneal curvature and hysteresis loop area (HLA) provided the best predictive value for Marfan syndrome (AUROC = 0.85). Conclusions This study describes novel biodynamic features of corneal deformation responses in Marfan syndrome, including increased deformation, decreased bending resistance, and decreased energy dissipation capacity. A predictive model incorporating HLA and corneal curvature shows greatest potential for non-invasive clinical diagnosis of Marfan syndrome. PMID:26432567

Generation of corneal epithelial cells from induced pluripotent stem cells derived from human dermal fibroblast and corneal limbal epithelium.

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Ryuhei Hayashi

Full Text Available Induced pluripotent stem (iPS cells can be established from somatic cells. However, there is currently no established strategy to generate corneal epithelial cells from iPS cells. In this study, we investigated whether corneal epithelial cells could be differentiated from iPS cells. We tested 2 distinct sources: human adult dermal fibroblast (HDF-derived iPS cells (253G1 and human adult corneal limbal epithelial cells (HLEC-derived iPS cells (L1B41. We first established iPS cells from HLEC by introducing the Yamanaka 4 factors. Corneal epithelial cells were successfully induced from the iPS cells by the stromal cell-derived inducing activity (SDIA differentiation method, as Pax6(+/K12(+ corneal epithelial colonies were observed after prolonged differentiation culture (12 weeks or later in both the L1B41 and 253G1 iPS cells following retinal pigment epithelial and lens cell induction. Interestingly, the corneal epithelial differentiation efficiency was higher in L1B41 than in 253G1. DNA methylation analysis revealed that a small proportion of differentially methylated regions still existed between L1B41 and 253G1 iPS cells even though no significant difference in methylation status was detected in the specific corneal epithelium-related genes such as K12, K3, and Pax6. The present study is the first to demonstrate a strategy for corneal epithelial cell differentiation from human iPS cells, and further suggests that the epigenomic status is associated with the propensity of iPS cells to differentiate into corneal epithelial cells.

In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal biomechanics assessed in-vitro. An animal pilot study.

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Rogala, Maja M; Danielewska, Monika E; Antończyk, Agnieszka; Kiełbowicz, Zdzisław; Rogowska, Marta E; Kozuń, Marta; Detyna, Jerzy; Iskander, D Robert

2017-09-01

The aim was to ascertain whether the characteristics of the corneal pulse (CP) measured in-vivo in a rabbit eye change after short-term artificial increase of intraocular pressure (IOP) and whether they correlate with corneal biomechanics assessed in-vitro. Eight New Zealand white rabbits were included in this study and were anesthetized. In-vivo experiments included simultaneous measurements of the CP signal, registered with a non-contact method, IOP, intra-arterial blood pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP. Afterwards, thickness of post-mortem corneas was determined and then uniaxial tensile tests were conducted leading to estimates of their Young's modulus (E). At the baseline IOP, backward stepwise regression analyses were performed in which successively the ocular biomechanical, biometric and cardiovascular predictors were separately taken into account. Results of the analysis revealed that the 3rd CP harmonic can be statistically significantly predicted by E and central corneal thickness (Models: R 2  = 0.662, p biomechanics in-vitro was confirmed. In particular, spectral analysis revealed that higher amplitude and power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP harmonic correlates positively with the corresponding harmonic of the BPL signal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Corneal topography with an aberrometry-topography system.

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Mülhaupt, Michael; Dietzko, Sven; Wolffsohn, James; Bandlitz, Stefan

2018-05-07

To investigate the agreement between the central corneal radii and corneal eccentricity measurements generated by the new Wave Analyzer 700 Medica (WAV) compared to the Keratograph 4 (KER) and to test the repeatability of the instruments. 20 subjects (10 male, mean age 29.1 years, range 21-50 years) were recruited from the students and staff of the Cologne School of Optometry. Central corneal radii for the flat (r c/fl ) and steep (r c/st ) meridian as well as corneal eccentricity for the nasal (e nas ), temporal (e temp ), inferior (e inf ) and superior (e sup ) directions were measured using WAV and KER by one examiner in a randomized order. Central radii of the flat (r c/fl ) and steep (r c/st ) meridian measured with both instruments were statically significantly correlated (r = 0.945 and r = 0.951; p  0.05). Limits of agreement (LoA) indicate a better repeatability for the KER compared to WAV. Corneal topography measurements captured with the WAV were strongly correlated with the KER. However, due to the differences in measured corneal radii and eccentricities, the devices cannot be used interchangeably. For corneal topography the KER demonstrated better repeatability. Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Corneal regeneration by induced human buccal mucosa cultivated on an amniotic membrane following alkaline injury.

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Man, Rohaina Che; Yong, Then Kong; Hwei, Ng Min; Halim, Wan Haslina Wan Abdul; Zahidin, Aida Zairani Mohd; Ramli, Roszalina; Saim, Aminuddin Bin; Idrus, Ruszymah Binti Hj

2017-01-01

Various clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE : The aims of this study were to differentiate human buccal mucosa (BMuc) into corneal epithelial-like cells, to fabricate engineered corneal tissue using buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium in a nude rat model. BMuc were subjected to 10 d of induction factors to investigate the potential of cells to differentiate into corneal lineages. Corneal stem cell markers β1-integrin, C/EBPδ, ABCG2, p63, and CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3 and p63 showed significant protein expression in induced BMuc compared to the uninduced cells. BMuc were then left to reach 80% confluency after differential trypsinization. The cells were harvested and cultivated on a commercially available untreated air-dried amniotic membrane (AM) in a Transwell system in induction medium. The corneal constructs were fabricated and then implanted into damaged rat corneas for up to 8 weeks. A significant improvement was detected in the treatment group at 8 weeks post-implantation, as revealed by slit lamp biomicroscopy analysis. The structure and thickness of the corneal layer were also analyzed using histological staining and time-domain optical coherence tomography scans and were found to resemble a native corneal layer. The protein expression for CK3 and p63 were continuously detected throughout the corneal epithelial layer in the corneal construct. In conclusion, human BMuc can be induced to express a corneal epithelial-like phenotype. The addition of BMuc improves corneal clarity, prevents vascularization, increases corneal thickness and stromal alignment, and appears to have no adverse effect on the host after implantation.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

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Zhao-Qin Hao

2016-11-01

Full Text Available AIM: To observe the therapeutic effect of corneal collagen cross-linking (CXL in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS: New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each. The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM at 4wk. RESULTS: A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P<0.05. The corneal epithelium defect areas of the combined group was smaller than that of the CXL group (P<0.05 on 7 and 14d, but there were no statistical differences on 3, 21 and 28d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28d. The diameters of the corneal collagen fiber bundles (42.960±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group were thicker than that of the control group (24.900±1.868 nm, but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION: CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.

Rechazo y retrasplante corneal Corneal rejection and re-transplantation

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Miguel O Mokey Castellanos

2007-06-01

Full Text Available Se efectuó una investigación observacional análítica retrospectiva, sobre los transplantes corneales efectuados en el Servicio de Oftalmología del Hospital "Hermanos Ameijeiras. Rechazaron 76 pacientes, que se compararon con un control de 89 pacientes, que en un período similar no tuvieron rechazo. El queratocono fue la afección corneal que predominó. El primer lugar en los rechazos correspondió a queratoherpes (43,5 %. El menor índice de rechazo fue para el queratocono (8,8 %. Se analizó la multiplicidad de rechazos; y fue frecuente que se presentara un solo rechazo, aunque sí hubo congruencia entre el número de rechazos y la necesidad de retrasplantes. Se encontró que los resultados de la conducta médica o quirúrgica se relacionaban con la causa. Se calcula un índice de supervivencia (Kaplan-Meier, que concluye que en los primeros dos años existe menos posibilidad de aparición de rechazoAn retrospective observational analytical research was conducted on corneal transplants performed at Ophthalmological Service in “Hermanos Ameijeiras” hospital . Seventy six patients had graft rejection and were compared to a control group of 89 patients that did not present rejection in the same period of time. Keratoconus was the prevailing corneal problem. The highest rejection rate corresponded to keratoherpes (43,5% whereas the lowest rate was for keratoconus (8,8%. Multiplicity of rejections was analyzed and it was found that mostly one graft rejection occured, but number of rejections was associated with the need of re-transplantation. It was found that the results of medical or surgical performance were related to the cause of graft rejection. A survival index (Kaplan-Meier was estimated, which showed that occurence of graf rejection is less probable in the first two years

Granular corneal dystrophy

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Castillo Pérez, Alexeide de la C; Vilches Lescaille, Daysi; Noriega, Justo Luis; Martínez Balido, Daneel; León Balbón, Bárbaro Ramón; León Bernal, Danysleidi

2015-01-01

Las distrofias corneales constituyen un conjunto de enfermedades que presentan, en su mayoría, una baja incidencia y se caracterizan por acúmulo de material hialino o amiloide que disminuyen la transparencia corneal. La distrofia granular es una enfermedad autosómica dominante que presenta opacidades grises en el estroma superficial central de la córnea y se hacen visibles en la primera y segunda décadas de la vida, lo que provoca disminución de la visión más significativa cerca de los 40 año...

Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

International Nuclear Information System (INIS)

Wheeler, D. L.; Verma, A. K.; Denning, M. F.

2013-01-01

The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

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Matthew E. Brown

2018-04-01

Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

Prevalence and causes of corneal blindness.

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Wang, Haijing; Zhang, Yaoguang; Li, Zhijian; Wang, Tiebin; Liu, Ping

2014-04-01

The study aimed to assess the prevalence and causes of corneal blindness in a rural northern Chinese population. Cross-sectional study. The cluster random sampling method was used to select the sample. This population-based study included 11 787 participants of all ages in rural Heilongjiang Province, China. These participants underwent a detailed interview and eye examination that included the measurement of visual acuity, slit-lamp biomicroscopy and direct ophthalmoscopy. An eye was considered to have corneal blindness if the visual acuity was blindness and low vision. Among the 10 384 people enrolled in the study, the prevalence of corneal blindness is 0.3% (95% confidence interval 0.2-0.4%). The leading cause was keratitis in childhood (40.0%), followed by ocular trauma (33.3%) and keratitis in adulthood (20.0%). Age and illiteracy were found to be associated with an increased prevalence of corneal blindness. Blindness because of corneal diseases in rural areas of Northern China is a significant public health problem that needs to be given more attention. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

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Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Applanation optical coherence elastography: noncontact measurement of intraocular pressure, corneal biomechanical properties, and corneal geometry with a single instrument

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Singh, Manmohan; Han, Zhaolong; Nair, Achuth; Schill, Alexander; Twa, Michael D.; Larin, Kirill V.

2017-02-01

Current clinical tools provide critical information about ocular health such as intraocular pressure (IOP). However, they lack the ability to quantify tissue material properties, which are potent markers for ocular tissue health and integrity. We describe a single instrument to measure the eye-globe IOP, quantify corneal biomechanical properties, and measure corneal geometry with a technique termed applanation optical coherence elastography (Appl-OCE). An ultrafast OCT system enabled visualization of corneal dynamics during noncontact applanation tonometry and direct measurement of micro air-pulse induced elastic wave propagation. Our preliminary results show that the proposed Appl-OCE system can be used to quantify IOP, corneal biomechanical properties, and corneal geometry, which builds a solid foundation for a unique device that can provide a more complete picture of ocular health.

Risk factors for corneal ectasia after LASIK.

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Tabbara, Khalid F; Kotb, Amgad A

2006-09-01

To establish a grading system that helps identify high-risk individuals who may experience corneal ectasia after LASIK. Retrospective, comparative, interventional case series. One hundred forty-eight consecutive patients (148 eyes) were included in this study. Thirty-seven patients who underwent LASIK at other refractive centers experienced corneal ectasia in 1 eye after LASIK. One hundred eleven eyes of 111 patients who underwent successful LASIK during the same period were age and gender matched and served as controls. All patients underwent preoperative and postoperative topographic analysis of the cornea. The follow-up period in both groups of patients ranged from 2 to 5 years, with a mean follow-up of 3.6 years. All patients underwent LASIK for myopia (spherical equivalent, -4.00 to -8.00 diopters). Corneal keratometry, oblique cylinder, pachymetry, posterior surface elevation, difference between the inferior and superior corneal diopteric power, and posterior best sphere fit (BSF) over anterior BSF were given a grade of 1 to 3 each. An ectasia grading system was established, and the cumulative risk score was assessed. Patients who had a grade of 7 or less showed no evidence of corneal ectasia, whereas 16 (59%) of 27 patients who had a grade of 8 to 12 had corneal ectasia. Twenty-one (100%) of 21 patients with a grade of more than 12 had corneal ectasia after LASIK (P<0.0001). A risk score may help in the prediction of patients who are at risk of experiencing corneal ectasia after LASIK. A prospective clinical study is needed to assess the validity of these risk factors.

Customized toric intraocular lens implantation for correction of extreme corneal astigmatism due to corneal scarring

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R Bassily

2010-03-01

Full Text Available R Bassily, J LuckOphthalmology Department, Royal United Hospital, Combe Park, Bath, UKAbstract: A 76-year-old woman presented with decreased visual function due to cataract formation. Twenty-five years prior she developed right sided corneal ulceration that left her with 10.8 diopters (D of irregular astigmatism at 71.8° (steep axis. Her uncorrected visual acuity was 6/24 and could only ever wear a balanced lens due to the high cylindrical error. Cataract surgery was planned with a custom designed toric intraocular lens (IOL with +16.0 D sphere inserted via a wound at the steep axis of corneal astigmatism. Postoperative refraction was -0.75/+1.50 × 177° with a visual acuity of 6/9 that has remained unchanged at six-week follow-up with no IOL rotation. This case demonstrates the value of high power toric IOLs for the correction of pathological corneal astigmatism.Keywords: intraocular lens, corneal ulceration, visual acuity, scarring

Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

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Li Cui

2014-06-01

Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection.

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Tabbara, Khalid F

2008-06-01

Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

Study on the establishment of corneal alkali chemical injury on rats

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Nan Hu

2013-06-01

Full Text Available AIM:To investigate the appropriate methods to establish corneal alkali chemical injury on rats. METHODS:The rats(n=87were randomly divided into three groups. Corneal alkali injury was induced by placing 1mol/L NaOH soaked filter paper on the limbus of right cornea for 20 seconds(group A, n=34or 40 seconds(group B, n=23, and on the central axis of the right cornea for 40 seconds(group C, n=30respectively. Corneal transparency, corneal ulceration, and corneal neovascularization were observed and recorded under slit- lamp biomicroscope on day 7 post-operation. RESULTS: Incidence of corneal ulceration, corneal perforation and positive rate of corneal fluorescein staining in limbal corneal injury groups(group A and Bwere significantly higher than that of central corneal injury group(group C(P<0.05. Incidence of corneal ulceration and corneal perforation in group B was significantly higher than group A(P<0.05. Corneal neovascularization was observed in all three groups. CONCLUSION: Corneal alkali burns induced by 3mm diameter central cornea injury are fit for the study of corneal neovascularization, while those induced by limbus injury for 20 seconds are fit for the study on limbal stem cells deficiency.

Punctiform and Polychromatophilic Dominant Pre-Descemet Corneal Dystrophy.

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Lagrou, Lisa; Midgley, Julian; Romanchuk, Kenneth Gerald

2016-04-01

To describe the slit-lamp appearance and corneal confocal microscopy of autosomal dominant punctiform and polychromatophilic pre-Descemet corneal dystrophy in 3 members of the same family. Slit-lamp examination of a 9-year-old boy showed bilateral polychromatophilic corneal opacities in a pre-Descemet membrane location evenly deposited limbus to limbus, both horizontally and vertically, with an intervening clear cornea. The corneal endothelium was normal on corneal confocal microscopy, with hyperreflective opacities of various sizes located pre-Descemet membrane. Slit-lamp examination of the patient's father and brother revealed identical crystalline deposition in the pre-Descemet corneal stroma. The remainders of the eye examinations were otherwise normal in all 3 individuals, and all were asymptomatic. The general physical examination and laboratory investigations of the patient were all normal, as were the laboratory investigations of the other 2 family members. There was no progression in the corneal findings over 6 months of follow-up. These patients likely illustrate a rare autosomal dominant pre-Descemet crystalline keratopathy that has been reported only once previously.

Recovery of Corneal Endothelial Cells from Periphery after Injury.

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Sang Ouk Choi

Full Text Available Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury.To investigate the recovery process of corneal endothelial cells (CECs from corneal endothelial injury.Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group. Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue.Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal.CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium.

Dual-model automatic detection of nerve-fibres in corneal confocal microscopy images.

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Dabbah, M A; Graham, J; Petropoulos, I; Tavakoli, M; Malik, R A

2010-01-01

Corneal Confocal Microscopy (CCM) imaging is a non-invasive surrogate of detecting, quantifying and monitoring diabetic peripheral neuropathy. This paper presents an automated method for detecting nerve-fibres from CCM images using a dual-model detection algorithm and compares the performance to well-established texture and feature detection methods. The algorithm comprises two separate models, one for the background and another for the foreground (nerve-fibres), which work interactively. Our evaluation shows significant improvement (p approximately 0) in both error rate and signal-to-noise ratio of this model over the competitor methods. The automatic method is also evaluated in comparison with manual ground truth analysis in assessing diabetic neuropathy on the basis of nerve-fibre length, and shows a strong correlation (r = 0.92). Both analyses significantly separate diabetic patients from control subjects (p approximately 0).

Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye.

Science.gov (United States)

Choi, Won; Lee, Jee Bum; Cui, Lian; Li, Ying; Li, Zhengri; Choi, Ji Suk; Lee, Hyo Seok; Yoon, Kyung Chul

2016-01-01

Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P model mice.

Behavioral phenotypes of genetic mouse models of autism.

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Kazdoba, T M; Leach, P T; Crawley, J N

2016-01-01

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Evaluation of corneal symmetry after UV corneal crosslinking for keratoconus

Directory of Open Access Journals (Sweden)

Mofty H

2017-11-01

Full Text Available Hanan Mofty,1,2 Khaled Alzahrani,2 Fiona Carley,3 Sophie Harper,3 Arun Brahma,3 Leon Au,3 Debbie Morley,3 M Chantal Hillarby2 1Optometry Department, College of Applied Medical Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 3Manchester Royal Eye Hospital, Manchester, UK Purpose: The purpose of this study was to assess UV corneal crosslinking (CXL treatment outcomes for keratoconus by evaluating the corneal regularity in patients through follow-up using the Oculus Pentacam.Patients and methods: A total of 18 eyes from CXL patients with keratoconus were studied before and after CXL treatment, and six eyes from six patients who were not treated with CXL served as controls. Treated patients had Pentacam images taken before CXL treatment and regularly 3 months post treatment up to the 12th month. Controls were imaged during their first appointment and after 12 months. Symmetry and asphericity were evaluated and correlated with both best-corrected visual acuity (BCVA and maximum K-readings.Results: In the CXL-treated group, there was a significant improvement in the index of symmetrical variation (ISV and keratoconus index (KI at 3 months and in the index of height asymmetry (IHA and minimum radius of curvature (Rmin at 9 months post treatment. On the contrary, the untreated group’s indices showed some significant worsening in ISV, KI, central keratoconus index (CKI, and Rmin. A novel finding in our study was a slight positive shift of anterior asphericity in the 6 mm, 7 mm, and 8 mm 3 months after treatment, which had a correlation with BCVA (R2=0.390, p=0.053 and a strong correlation with maximum K-reading (R2=0.690, p=0.005. However, the untreated group had no significant changes after 1 year.Conclusion: The corneal asymmetrical shape is associated with the spherical aberration alteration

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

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Zhu, Wei; Han, Yunfei; Cui, Changxia; Xu, Wenwen; Wang, Xuan; Dou, Xiaoxiao; Xu, Linlin; Xu, Yanyun; Mu, Guoying

2018-01-01

The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p 0.05) beyond 6 months after treatment. PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement. © 2018 S. Karger AG, Basel.

Parametric fitting of corneal height data to a biconic surface.

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Janunts, Edgar; Kannengießer, Marc; Langenbucher, Achim

2015-03-01

As the average corneal shape can effectively be approximated by a conic section, a determination of the corneal shape by biconic parameters is desired. The purpose of the paper is to introduce a straightforward mathematical approach for extracting clinically relevant parameters of corneal surface, such as radii of curvature and conic constants for principle meridians and astigmatism. A general description for modeling the ocular surfaces in a biconic form is given, based on which an implicit parametric surface fitting algorithm is introduced. The solution of the biconic fitting is obtained by a two sequential least squares optimization approach with constrains. The data input can be raw information from any corneal topographer with not necessarily a uniform data distribution. Various simulated and clinical data are studied including surfaces with rotationally symmetric and non-symmetric geometries. The clinical data was obtained from the Pentacam (Oculus) for the patient having undergone a refractive surgery. A sub-micrometer fitting accuracy was obtained for all simulated surfaces: 0,08 μm RMS fitting error at max for rotationally symmetric and 0,125 μm for non-symmetric surfaces. The astigmatism was recovered in a sub-minutes resolution. The equality in rotational symmetric and the superiority in non-symmetric surfaces of the presented model over the widely used quadric fitting model is shown. The introduced biconic surface fitting algorithm is able to recover the apical radii of curvature and conic constants in principle meridians. This methodology could be a platform for advanced IOL calculations and enhanced contact lens fitting. Copyright © 2014. Published by Elsevier GmbH.

A new 3D reconstituted human corneal epithelium model as an alternative method for the eye irritation test.

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Jung, Kyoung-Mi; Lee, Su-Hyon; Ryu, Yang-Hwan; Jang, Won-Hee; Jung, Haeng-Sun; Han, Ju-Hee; Seok, Seung-Hyeok; Park, Jae-Hak; Son, Youngsook; Park, Young-Ho; Lim, Kyung-Min

2011-02-01

Many efforts are being made to develop new alternative in vitro test methods for the eye irritation test. Here we report a new reconstructed human corneal epithelial model (MCTT HCE model) prepared from primary-cultured human limbal epithelial cells as a new alternative in vitro eye irritation test method. In histological and immunohistochemical observation, MCTT HCE model displayed a morphology and biomarker expressions similar to intact human cornea. Moreover, the barrier function was well preserved as measured by high transepithelial electrical resistance, effective time-50 for Triton X-100, and corneal thickness. To employ the model as a new alternative method for eye irritation test, protocol refinement was performed and optimum assay condition was determined including treatment time, treatment volume, post-incubation time and rinsing method. Using the refined protocol, 25 reference chemicals with known eye irritation potentials were tested. With the viability cut-off value at 50%, chemicals were classified to irritant or non-irritant. When compared with GHS classification, the MCTT HCE model showed the accuracy of 88%, sensitivity of 100% and specificity of 77%. These results suggest that the MCTT HCE model might be useful as a new alternative eye irritation test method. Copyright © 2010 Elsevier Ltd. All rights reserved.

Corneal Laceration

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Full Text Available ... to Full Corneal Transplantation Nov 29, 2016 Follow The Academy Professionals: Education Guidelines News Multimedia Public & Patients: Contact Us About the Academy Jobs at the Academy Financial Relationships with Industry ...

Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model.

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Gore, Ariel; Horwitz, Vered; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Gez, Rellie; Kadar, Tamar; Dachir, Shlomit

2018-03-13

To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks. Non-treated exposed eyes served as a control. A clinical follow-up employed by slit-lamp microscope, was performed up to 12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessels length using the image analysis software. Eyes were taken for histological evaluation 2, 4 and 8 weeks following treatment for general morphology and for visualization of NV, using H&E and Masson Trichrome stainings, while conjunctival goblet cell density was determined by PAS staining. Corneal NV developed, starting as early as two weeks after exposure. A single subconjunctival treatment of ziv-aflibercept at 4 weeks post exposure, significantly reduced the extent of existing NV already one week following injection, an effect which lasted for at least 8 weeks following treatment, while NV in the non-treated exposed eyes continued to advance. The extensive reduction in corneal NV in the ziv-aflibercept treated group was confirmed by histological evaluation. Bevacizumab multiple treatment showed a benefit in NV reduction, but to a lesser extent compared to the ziv-aflibercept treatment. Finally, ziv-aflibercept increased the density of conjunctival goblet cells as compared to the exposed non-treated group. Subconjunctival ziv-aflibercept single treatment presented a highly efficient long-term therapeutic benefit in reducing existing corneal NV, following ocular sulfur mustard exposure. These findings show the robust anti-angiogenic efficacy of ziv

The leaves of Diospyros kaki exert beneficial effects on a benzalkonium chloride-induced murine dry eye model.

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Kim, Kyung-A; Hyun, Lee Chung; Jung, Sang Hoon; Yang, Sung Jae

2016-01-01

In this study, the beneficial effects of the oral administration of ethanol extract of Diospyros kaki (EEDK) were tested on a mouse dry eye model induced by benzalkonium chloride (BAC). A solution of 0.2% BAC was administered topically to mouse eyes for 14 days, twice daily, to induce dry eye. Various concentrations of EEDK were administrated daily by oral gavage for 14 days after BAC treatment. Preservative-free eye drops were instilled in the positive-control group. The tear secretion volume (Schirmer's test), tear break-up time (BUT), and fluorescein score were measured on the ocular surface. BAC-induced corneal damage was tested with hematoxylin-eosin staining. Moreover, apoptotic cell death in the corneal epithelial layer was investigated with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The protein expression level of interleukin-1alpha (IL-1α), IL-1β, IL-6, tumor necrosis factor- alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1) was determined with western blot analysis. Furthermore, squamous metaplasia in the corneal epithelial layer was detected with immunofluorescent staining for cytokeratine-10. The cellular proliferation in the cornea was examined with immunohistochemical staining for Ki-67. EEDK treatment resulted in prolonged BUT, decreased fluorescein score, increased tear volume, and smoother epithelial cells compared with BAC treatment alone in the cornea. Moreover, EEDK treatment inhibited the inflammatory response and corneal epithelial cell death in a BAC-induced murine dry eye model, and changes in squamous cells were inhibited. Proliferative activity in the corneal epithelium cells was improved with EEDK. EEDK could be a potential therapeutic agent in the clinical treatment of dry eye.

Rapamycin Eye Drops Suppress Lacrimal Gland Inflammation In a Murine Model of Sjögren's Syndrome

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Shah, Mihir; Edman, Maria C.; Reddy Janga, Srikanth; Yarber, Frances; Meng, Zhen; Klinngam, Wannita; Bushman, Jonathan; Ma, Tao; Liu, Siyu; Louie, Stan; Mehta, Arjun; Ding, Chuanqing; MacKay, J. Andrew; Hamm-Alvarez, Sarah F.

2017-01-01

Purpose To evaluate the efficacy of topical rapamycin in treating autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. Methods We developed rapamycin in a poly(ethylene glycol)-distearoyl phosphatidylethanolamine (PEG-DSPE) micelle formulation to maintain solubility. Rapamycin or PEG-DSPE eye drops (vehicle) were administered in a well-established Sjögren's syndrome disease model, the male nonobese diabetic (NOD) mice, twice daily for 12 weeks starting at 8 weeks of age. Mouse tear fluid was collected and tear Cathepsin S, a putative tear biomarker for Sjögren's syndrome, was measured. Lacrimal glands were retrieved for histological evaluation, and quantitative real-time PCR of genes associated with Sjögren's syndrome pathogenesis. Tear secretion was measured using phenol red threads, and corneal fluorescein staining was used to assess corneal integrity. Results Lymphocytic infiltration of lacrimal glands from rapamycin-treated mice was significantly (P = 0.0001) reduced by 3.8-fold relative to vehicle-treated mice after 12 weeks of treatment. Rapamycin, but not vehicle, treatment increased tear secretion and decreased corneal fluorescein staining after 12 weeks. In rapamycin-treated mice, Cathepsin S activity was significantly reduced by 3.75-fold in tears (P eye. PMID:28122086

Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression

International Nuclear Information System (INIS)

Yu Hui; Wu Jihong; Li Huiming; Wang Zhanli; Chen Xiafang; Tian Yuhua; Yi Miaoying; Ji Xunda; Ma Jialie; Huang Qian

2007-01-01

The interaction of vascular endothelial growth factor (VEGF) and its receptors (Flt-1, Flk-1/KDR) is correlated with neovascularization in the eyes. Therefore, blocking the binding of VEGF and the corresponding receptor has become critical for inhibiting corneal neovascularization. In this study, we have expressed the cDNA for sFlk-1 under the control of cytomegalovirus immediate-early promoter (CMV) from an E1/partial E3 deleted replication defective recombinant adenovirus, and Ad.sflk-1 expression was determined by Western blotting. We have shown that conditioned media from Ad.sflk-1-infected ARPE-19 cells significantly reduced VEGF-induced human umbilical vein endothelial cells (HUVEC) and murine endothelial cells (SVEC) proliferation in vitro compared with the control vector. In vivo, adenoviral vectors expressing green fluorescent protein alone (Ad.GFP) were utilized to monitor gene transfer to the cornea. Moreover, in the models of corneal neovascularization, the injection of Ad.sflk-1 (10 8 PFU) into the anterior chamber could significantly inhibit angiogenic changes compared with Ad.null-injected and vehicle-injected models. Immunohistochemical analysis showed that corneal endothelial cells and corneal stroma of cauterized rat eyes were efficiently transduced and expressed sFlk-1. These results not only support that adenoviral vectors are capable of high-level transgene expression but also demonstrate that Ad.sflk-1 gene therapy might be a feasible approach for inhibiting the development of corneal neovascularization

Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival.

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Liu, Zhaochuan; Lin, Haotian; Huang, Chulong; Chen, Wan; Xiang, Wu; Geng, Yu; Chen, Weirong

2015-11-12

Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution are also unknown. Thus, we developed 0.1%, 0.2% and 0.5% FTY720 ophthalmic solutions and evaluated their chemical stabilities under various storage conditions with high- performance liquid chromatography. To investigate the ocular irritancy of the FTY720 ophthalmic solution, New Zealand albino rabbits were subjected to the Draize test. Furthermore, classic, well-established rat allogenic penetrating keratoplasty models were used to investigate the anti-rejection efficacy of the tested FTY720 ophthalmic solutions. We found that the non-irritating 0.5% FTY720 ophthalmic solution could prolong corneal allograft survival in rats with significant efficacy for about one month. Furthermore, no significant concentration changes occurred in any of the types of FTY720 ophthalmic solutions within three months. These results revealed crucial profiles of FTY720 ophthalmic solutions and warrant further investigation and optimization of FTY720 in the anti-rejection therapy after keratoplasty.

Using corneal topography design personalized cataract surgery programs

Directory of Open Access Journals (Sweden)

Jin-Ou Huang

2014-08-01

Full Text Available AIM:To investigate how to design personalized cataract surgery programs to achieve surgical correction of preoperative corneal astigmatism with surgical astigmatism under the guidance of corneal topography, improve postoperative visual quality and reduce the cost of treatment. METHODS: Totally 202 cases(226 eyescataract patients were divided into randomized treatment group and individualized treatment group. According to the method and location of the incision, randomized treatment group were divided into 8 groups. Surgical astigmatism after different incision were calculated with the use of preoperative and postoperative corneal astigmatism through vector analysis method. Individualized treatment groups were designed personably for surgical method with reference of every surgically induced astigmatism, the surgical method chooses the type of surgical incision based on close link between preoperative corneal astigmatism and surgically induced astigmatism, and the incision was located in the steep meridian. The postoperative corneal astigmatism of individualized treatment group was observed. RESULTS: Postoperative corneal astigmatism of individualized treatment group were lower than that of 3.0mm clear corneal tunnel incision in the randomized treatment group, there were statistically significance difference, while with 3.0mm sclera tunnel incision group there were no statistically significance difference. After 55.8% of patients with the use of individualized surgical plan could undergo the operation of extracapsular cataract extraction with relatively low cost and rigid intraocular lens implantation, the per capita cost of treatment could be reduced. CONCLUSION: Personalized cataract surgery programs are designed to achieve surgical correction of preoperative corneal astigmatism under the use of corneal topography, improve postoperative visual quality and reduce the cost of treatment.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Directory of Open Access Journals (Sweden)

Rosa Dolz-Marco

2014-01-01

Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Science.gov (United States)

Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

2014-01-01

Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

Corneal structure and transparency

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Meek, Keith M.; Knupp, Carlo

2015-01-01

The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

Topical Ranibizumab as a Treatment of Corneal Neovascularization

Science.gov (United States)

Ferrari, Giulio; Dastjerdi, Mohammad H.; Okanobo, Andre; Cheng, Sheng-Fu; Amparo, Francisco; Nallasamy, Nambi; Dana, Reza

2014-01-01

Purpose To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods This was a prospective, open-label, monocentric, uncontrolled, non-comparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up of 16 weeks. The main corneal neovascularization outcome measures were: neovascular area (NA), the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Results Statistically significant decreases in NA (55.3%, P<0.001), which lasted through 16 weeks, and VC (59%, P<0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P=0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA. PMID:23407316

Corneal changes with accommodation using dual Scheimpflug photography.

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Sisó-Fuertes, Irene; Domínguez-Vicent, Alberto; del Águila-Carrasco, Antonio; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2015-05-01

To assess whether corneal parameters and aberrations are affected by accommodation. Optics Department, University of Valencia, Valencia, Spain. Prospective cross-sectional study. The Galilei G4 dual Scheimpflug device was used to obtain data on the anterior and posterior axial curvatures, total corneal power (TCP), and corneal pachymetry from 3 corneal zones (central: 0.0 up to 4.0 mm; paracentral or mid: 4.0 up to 7.0 mm; peripheral: 7.0 up to 10.0 mm) in young emmetropic eyes in the unaccommodated and 4 accommodated states (from -1.0 to -4.0 diopters [D] in 1.0 D steps). The 2nd-, 3rd-, and 4th-order aberrations as well as the root mean square (RMS) were also determined for the entire cornea at the same accommodative demands. The study evaluated 7 subjects (12 eyes). No significant changes in any measured parameter were found during accommodation for any corneal zone (P > .05). Statistically significant differences were found in the various corneal zones when it was assumed they were constant with accommodation (P the high standard deviation values. Different parameters in various zones of the cornea as well as corneal aberrations were stable during accommodation. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications

Science.gov (United States)

Ambrósio, Jr, Renato; Correia, Fernando Faria; Lopes, Bernardo; Salomão, Marcella Q.; Luz, Allan; Dawson, Daniel G.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Roberts, Cynthia J.

2017-01-01

Background: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. Method: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. Conclusions: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy. PMID:28932334

Corneal biomechanical properties in healthy children measured by corneal visualization scheimpflug technology.

Science.gov (United States)

He, Miao; Ding, Hui; He, Hong; Zhang, Chi; Liu, Liangping; Zhong, Xingwu

2017-05-17

The aim of this study was to evaluate corneal biomechanical properties in a population of healthy children in China using corneal visualization Scheimpflug technology (CST). All children underwent complete bi-ocular examinations. CST provided intraocular pressure (IOP) and corneal biomechanical parameters, including time, velocity, length and deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC). Pearson correlation analysis was used to assess the impacts of demographic factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on corneal biomechanics. One hundred eight subjects (32 girls and 76 boys) with the mean age of 10.80 ± 4.13 years (range 4 to18 years) were included in the final analyses. The right and left eyes were highly symmetrical in SE (p = 0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424 ± 0.340 ms; the left eyes 7.451 ± 0.365 ms. MDA was 0.993 ± 0.102 mm in the right eyes and 0.982 ± 0.100 mm in the left eyes. Mean HCT of the right eyes was 16.675 ± 0.502 ms; the left eyes 16.735 ± 0.555 ms. All CST parameters of both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA (p = 0.025). The majority of CST parameters of both eyes were significantly correlated with CCT and IOP (p children eyes. Several CST biomechanical parameters in children are modified by CCT and IOP.

Corneal Laceration

Medline Plus

Full Text Available ... by something sharp flying into the eye. It can also be caused by something striking the eye ... If the corneal laceration is deep enough it can cause a full thickness laceration. This is when ...

Mouse Model of Burn Wound and Infection

DEFF Research Database (Denmark)

Calum, Henrik; Høiby, Niels; Moser, Claus

2017-01-01

The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr) a depres......The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr...

Alloimmunity and Tolerance in Corneal Transplantation.

Science.gov (United States)

Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

2016-05-15

Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. Copyright © 2016 by The American Association of Immunologists, Inc.

Comparison of postoperative corneal changes between dry eye and non-dry eye in a murine cataract surgery model.

Science.gov (United States)

Kwon, Jin Woo; Chung, Yeon Woong; Choi, Jin A; La, Tae Yoon; Jee, Dong Hyun; Cho, Yang Kyung

2016-01-01

To compare the effects of the surgical insult of cataract surgery on corneal inflammatory infiltration, neovascularization (NV) and lymphangiogenesis (LY) between the dry eye and non-dry eye in murine cataract surgery models. We established two groups of animals, one with normal eyes (non-dry eye) and the second with induced dry eyes. In both groups, we used surgical insults to mimic human cataract surgery, which consisted of lens extraction, corneal incision and suture. After harvesting of corneas on the 9(th) postoperative day and immunohistochemical staining, we compared NV, LY and CD11b+ cell infiltration in the corneas. Dry eye group had significantly more inflammatory infiltration (21.75%±7.17% vs 3.65%±1.49%; P=0.049). The dry eye group showed significantly more NV (48.21%±4.02% vs 26.24%±6.01%; P=0.016) and greater levels of LY (9.27%±0.48% vs 4.84%±1.15%; P=0.007). In corneas on which no surgery was performed, there was no induction of NV in both the dry and non-dry group, but dry eye group demonstrated more CD11b+ cells infiltration than the non-dry eye group (0.360%±0.160% vs 0.023%±0.006%; P=0.068). Dry eye group showed more NV than non-dry eye group in both topical PBS application and subconjunctival PBS injection (P=0.020 and 0.000, respectively). In a murine cataract surgery model, preexisting dry eye can induce more postoperative NV, LY, and inflammation in corneal tissue.

Influence of corneal parameters in keratoconus on IOP readings obtained with different tonometers.

Science.gov (United States)

Firat, Penpe Gul; Orman, Gozde; Doganay, Selim; Demirel, Soner

2013-03-01

Accurate intraocular pressure (IOP) measurement is important but of unsure reliability in patients with keratoconus. Different types and models of tonometers are available. This study investigated the influence of corneal parameters on IOP readings obtained by a Goldmann applanation tonometer, a non-contact tonometer and a dynamic contour tonometer. IOP readings with the Goldmann applanation, non-contact and dynamic contour tonometers were obtained from 52 patients with keratoconus and from 50 normal subjects and their corneal parameters were measured using a Pentacam. The mean IOP measurements in keratoconus obtained with the Goldmann applanation, non-contact and dynamic contour tonometers were statistically significantly different from the mean IOP measurements in the normal subjects (p contact tonometers but not on the dynamic contour tonometer. In the control group, thinnest and central corneal thicknesses had a significant effect on findings with the Goldmann and non-contact tonometers but not on the dynamic contour tonometer. The corneal volume (CV) had no significant effect on the three tonometers in both groups. The corneal parameters affecting the IOP readings of the Goldmann applanation tonometers, non-contact tonometers and the dynamic contour tonometers are not the same. While the Goldmann applanation and non-contact tonometers were significantly affected by the corneal parameters that were measured, the dynamic contour tonometer was not affected by any of these corneal parameters. © 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering.

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Jui-Yang Lai

Full Text Available Hyaluronic acid (HA is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function.

Corneal thickness: measurement and implications.

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Ehlers, Niels; Hjortdal, Jesper

2004-03-01

The thickness of the cornea was reported in more than 100-year-old textbooks on physiological optics (Helmholtz, Gullstrand). Physiological interest was revived in the 1950s by David Maurice, and over the next 50 years, this 'simple' biological parameter has been studied extensively. Several techniques for its measurement have been described and physiological and clinical significance have been studied. In this review, the different methods and techniques of measurement are briefly presented (optical, ultrasound). While the corneal thickness of many animals are the same over a considerable part of the surface, in the human cornea anterior and posterior curvature are not concentric giving rise to a problem of definition. Based on this the precision and accuracy of determining the central corneal thickness are discussed. Changes in corneal thickness reflects changes in function of the boundary layers, in particular the endothelial barrier. The absolute value of thickness is of importance for the estimation of IOP but also in diagnosis of corneal and systemic disorders. Finally it is discussed to what extent the thickness is a biometric parameter of significance, e.g. in the progression of myopia or in the development of retinal detachment.

Generation of Femtosecond Laser-Cut Decellularized Corneal Lenticule Using Hypotonic Trypsin-EDTA Solution for Corneal Tissue Engineering

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Man-Il Huh

2018-01-01

Full Text Available Purpose. To establish an optimized and standardized protocol for the development of optimal scaffold for bioengineering corneal substitutes, we used femtosecond laser to process human corneal tissue into stromal lenticules and studied to find the most efficient decellularization method among various reagents with different tonicities. Methods. The decellularization efficacy of several agents (0.1%, 0.25%, and 0.5% of Triton X-100, SDS, and trypsin-EDTA (TE, resp. with different tonicities was evaluated. Of all protocols, the decellularization methods, which efficiently removed nuclear materials examined as detected by immunofluorescent staining, were quantitatively tested for sample DNA and glycosaminoglycan (GAG contents, recellularization efficacy, and biocompatibilities. Results. 0.5% SDS in hypertonic and isotonic buffer, 0.25% TE in hypotonic buffer, and 0.5% TE in all tonicities completely decellularized the corneal lenticules. Of the protocols, decellularization with hypotonic 0.25 and 0.5% TE showed the lowest DNA contents, while the GAG content was the highest. Furthermore, the recellularization efficacy of the hypotonic TE method was better than that of the SDS-based method. Hypotonic TE-treated decellularized corneal lenticules (DCLs were sufficiently transparent and biocompatible. Conclusion. We generated an ideal protocol for DCLs using a novel method. Furthermore, it is possible to create a scaffold using a bioengineered corneal substitute.

Treatment Results of Corneal Collagen Cross-Linking Combined with Riboflavin and 440 Nm Blue Light for Bacterial Corneal Ulcer in Rabbits.

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Wei, Shufang; Zhang, Cuiying; Zhang, Shaoru; Xu, Yanyun; Mu, Guoying

2017-10-01

To study the treatment effect of corneal collagen cross-linking (CXL) combined with 440 nm blue light and riboflavin on bacterial corneal ulcer using animal experiments. A total of 21 New Zealand white rabbits that developed Staphylococcus aureus corneal ulcer were randomly divided into three groups. Seven rabbits were used as blank control groups; seven rabbits were treated with CXL combined with riboflavin and 440 nm blue light; and seven rabbits were treated with CXL combined with riboflavin and 370 nm ultraviolet A light. Necrotic tissues or secretions from the ulcer surface, eye secretions, conjunctival hyperemia, hypopyon, corneal infiltration, and pathological changes of the cornea were all observed. The 1st, 3th, and 7th day after CXL treatment, a statistically significant difference was found among the inflammation scores of the three groups. The scores of 440 and 370 groups decreased gradually, significantly lower than that of the control group. Bacterial cultures of 440 and 370 groups turned to be negative while that of the control group remained positive. After 1 day of CXL treatment, pathology pictures of the three groups all showed loss of corneal epithelia with many inflammatory cells in deep stroma. After 7 days of CXL treatment, abscess formed in almost all corneal area in the control group, while in 440 and 370 groups, multilayer healing of corneal epithelia, neovascularization, and many inflammatory cells within ulcers and proliferation of a small amount of fibroblast were seen. CXL combined with riboflavin and 440 nm blue light is effective in treating S. aureus corneal ulcer.

A Mouse Model of Chronic West Nile Virus Disease.

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Jessica B Graham

2016-11-01

Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

Hevin plays a pivotal role in corneal wound healing.

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Shyam S Chaurasia

Full Text Available BACKGROUND: Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK in hevin-null (hevin(-/- mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin to rescue the stromal cellular components damaged by the excimer laser. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and hevin (-/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM, transmission electron microscopy (TEM, immunohistochemistry (IHC and western blotting (WB. IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin (-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts, inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. CONCLUSIONS/SIGNIFICANCE: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin (-/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued

Esophageal Cancer: Insights from Mouse Models

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Marie-Pier Tétreault

2015-01-01

Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

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Hertsenberg, Andrew J; Funderburgh, James L

2016-01-01

Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

Clinical Validation of Point-Source Corneal Topography in Keratoplasty

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Vrijling, A C L; Braaf, B.; Snellenburg, J.J.; de Lange, F.; Zaal, M.J.W.; van der Heijde, G.L.; Sicam, V.A.D.P.

2011-01-01

Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using

Corneal donations in South Africa: A 15-year review.

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York, Nicholas J; Tinley, Christopher

2017-07-28

Corneal pathology is one of the leading causes of preventable blindness in South Africa (SA). A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem. To describe trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors. This was a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016. There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8% originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%. Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/Asian. Donor age demonstrated a bimodal peak at 25 and 55 years. The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.

Effect of Cycloplegia on Corneal Biometrics and Refractive State.

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Bagheri, Abbas; Feizi, Mohadeseh; Shafii, Aliakbar; Faramarzi, Amir; Tavakoli, Mehdi; Yazdani, Shahin

2018-01-01

To determine changes in refractive state and corneal parameters after cycloplegia with cyclopentolate hydrochloride 1% using a dual Scheimpflug imaging system. In this prospective cross-sectional study patients aged 10 to 40 years who were referred for optometric evaluation enrolled and underwent autorefraction and corneal imaging with the Galilei dual Scheimpflug system before and 30 minutes after twice instillation of medication. Changes in refraction and astigmatism were investigated. Corneal biometrics including anterior and posterior corneal curvatures, total corneal power and corneal pachymetry were compared before and after cycloplegia. Two hundred and twelve eyes of 106 subjects with mean age of 28 ± 5 years including 201 myopic and 11 hyperopic eyes were evaluated. Mean spherical equivalent refractive error before cycloplegia was -3.4 ± 2.6 D. A mean hyperopic shift of 0.4 ± 0.5 D occurred after cycloplegia ( P biometrics should be considered before cataract and refractive surgeries.

Using the mouse to model human disease: increasing validity and reproducibility

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Monica J. Justice

2016-02-01

Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

Corneal surface reconstruction - a short review

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Madhavan H N

2009-01-01

. Cells or tissues can be embedded in a liquid Mebiol gel solution at lower than 20°C and cultured three dimensionally in a hydrogel state at 37°C. The sol-gel transition temperature can be controlled by altering chemical composition of thermo-reversible gelation polymer (TGP. Mebiol Gel prevents the growth of the fibroblasts and it is not toxic to cells. In our earlier study, continuous culture cell lines 18 and we demonstrated that Mebiol Gel supported the growth of corneal limbal epithelial cells and these cells expressed both limbal and corneal phenotype, suggesting that limbal epithelial cells cultivated in Mebiol Gel would be a promising material for corneal surface tissue engineering. With this in view, we developed a novel method of cultivation of human limbal cells in a synthetic scaffold made of a thermo reversible polymer, that allows the limbal epithelial cells to survive, proliferate and differentiate into corneal epithelial cells and demonstrated the effectiveness of this polymer for corneal tissue engineering using an experimentally induced limbal deficiency in a rabbit model. In this report, the detailed procedure of the animal model and the results are discussed. We evaluated the efficacy of autologous expanded corneal epithelial cell transplants derived from harvested limbal biopsy cultured on a thermo-reversible polymer (Mebiol Gel for the management of unilateral limbal stem cell disease (LSCD.Corneal limbal biopsies from 12 rabbits were cultured on Mebiol Gel at 37°C. Cells were harvested from the dishes after 3 weeks by reducing temperature to 4°C. Autologous transplantation was undertaken to reconstruct the experimentally induced limbal stem cell deficiency in the rabbit eyes. The corneas of both eyes of all rabbits were harvested later for histological and RT-PCR studies. Reparative surgery was a total success in 7 (58.3%; score, 8-10, partial success in 2 (16.7%; score, 6-7 and failure in 3 (25%; score, <5. Histological and RT-PCR study

Surgically induced astigmatism after phacoemulsification by temporal clear corneal and superior clear corneal approach: a comparison

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Nikose AS

2018-01-01

Full Text Available Archana Sunil Nikose, Dhrubojyoti Saha, Pradnya Mukesh Laddha, Mayuri Patil Department of Ophthalmology, N.K.P. Salve Institute and LMH, Nagpur, Maharashtra, India Introduction: Cataract surgery has undergone various advances since it was evolved from ancient couching to the modern phacoemulsification cataract surgery. Surgically induced astigmatism (SIA remains one of the most common complications. The introduction of sutureless clear corneal incision has gained increasing popularity worldwide because it offers several advantages over the traditional sutured limbal incision and scleral tunnel. A clear corneal incision has the benefit of being bloodless and having an easy approach, but SIA is still a concern.Purpose: In this study, we evaluated the SIA in clear corneal incisions with temporal approach and superior approach phacoemulsification. Comparisons between the two incisions were done using keratometric readings of preoperative and postoperative refractive status.Methodology: It was a hospital-based prospective interventional comparative randomized control trial of 261 patients conducted in a rural-based tertiary care center from September 2012 to August 2014. The visual acuity and detailed anterior segment and posterior segment examinations were done and the cataract was graded according to Lens Opacification Classification System II. Patients were divided for phacoemulsification into two groups, group A and group B, who underwent temporal and superior clear corneal approach, respectively. The patients were followed up on day 1, 7, 30, and 90 postoperatively. The parameters recorded were uncorrected visual acuity, best-corrected visual acuity, slit lamp examination, and keratometry. The mean difference of SIA between 30th and 90th day was statistically evaluated using paired t-test, and all the analyses were performed using SPSS 18.0 (SPSS Inc. software.Results: The mean postoperative SIA in group A was 0.998 D on the 30th day, which

Experiment of amnion epithelial cell suspension liquid used for acute rabbit corneal alkali burn

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Yan-Yan Zhang

2017-10-01

Full Text Available AIM: To investigate the effects of amnion epithelial cell(AECsuspension liquid on the biological behavior of the rabbit's corneal epithelium, combined with the in vitro and in vivo experiments. METHODS: The rabbit's corneal epithelium were cultured in the lower chamber of transwell, and AEC suspension liquid was dropwised in the upper chamber. There was only culture medium in the upper chamber of the control group. The proliferation of rabbit's corneal epithelium was observed with CCK-8 automated colorimetry and the expression of PCNA was detected by immunocytochemistry. We used the scratch wound assay to detect the migration of corneal epithelial cell(CEC. The in vivo models were established by placing a 10mm diameter corneal trephine in the center of the cornea, within 1mol/L NaOH for 1min. We divided those into three groups: treatment group of AEC suspension liquid eye drop, AEC suspension liquid subconjunctival injection and the control group without any treatment. Using the slit-lamp biomicroscope and fluorescence staining to observe the cornea per week. After 28d we took the eyeballs with the HE staining. The expression of VEGF was detected by immunohistochemistry. RESULTS: The activity of CEC with AEC treatment was much higher than the control group(PPIn vivo, the inflammation of the corneal and the CNV of the AEC group were all significantly reduced compared with the control group(PPCONCLUSION: AEC suspension liquid can promote the proliferation and migration of the rabbit's corneal epithelium. The potential of AEC suspension liquid as a therapy for acute corneal alkali burn.

Serine protease inhibitor A3K suppressed the formation of ocular surface squamous metaplasia in a mouse model of experimental dry eye.

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Lin, Zhirong; Zhou, Yueping; Wang, Yuqian; Zhou, Tong; Li, Jie; Luo, Pingping; He, Hui; Wu, Huping; Liu, Zuguo

2014-08-07

To investigate the effects and possible mechanisms of serine protease inhibitor A3K (SERPINA3K) on the formation of ocular surface squamous metaplasia in a mouse dry eye model induced by topical benzalkonium chloride (BAC). The eye drops containing SERPINA3K were topically administered during the induction of BAC-induced dry eye. The clinical indications of dry eye were evaluated on day (D)16, including tear break-up time (BUT), tear volume, corneal fluorescein staining, and inflammatory index. Global specimens were collected on D16 and the following examinations were performed: histologic investigation, immunostaining of cytokeratin 10 (K10), p63 and Ki67 in the cornea, and Western blot analysis of tumor necrosis factor-α (TNF-α). Serine protease inhibitor A3K suppressed the formation of BAC-induced dry eye, presenting with longer BUTs, lower corneal fluorescein staining scores, and inflammatory index, while no significant changes in tear volume. It also reduced the severity of abnormal differentiation and proliferation on ocular surface with lower expressions of K10, p63, and Ki67, and retained the number of goblet cells in the conjunctival fornix. Serine protease inhibitor A3K significantly decreased the levels of TNF-α in the cornea. Topical application of SERPINA3K ameliorated the severity of ocular surface squamous metaplasia and suppressed the formation of BAC-induced dry eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Depósitos corneales de ciprofloxacino Corneal deposits of ciprofloxacin

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Taimi Cárdenas Díaz

2010-01-01

Full Text Available Las fluoroquinolonas son ampliamente utilizadas para el tratamiento de infecciones oculares bacterianas, ya que tienen actividad tanto para grampositivos, como para gramnegativos. Son fármacos seguros, pero se han descrito depósitos blancos cristalinianos en pacientes con administración frecuente y prolongada;en la mayoría de los casos, ellos resuelven de forma lenta al interrumpir el tratamiento. Si esto no ocurre, los depósitos se deben desbridar. Se ilustran 3 casos operados de catarata que llevaron tratamiento con ciprofloxacino en el posoperatorio, en los cuales se presentaron depósitos corneales y aunque disminuyó la agudeza visual, esta se recuperó después de la queratectomía.Fluoroquinolones are broadly used for the treatment of bacterial ocular infections, since they can act upon both grampositive and gramnegative bacteria. They are safe drugs, but white corneal deposits have been described in patients who frequently take this drug for a long period of time. In most of the cases, the deposits disappear slowly after the treatment is interrupted. If this does not happen, the deposits should be eliminated. Three cases operated on from cataract were presented, who had been taken ciprofloxacin in the postoperative stage and had corneal deposits. Although their visual acuity decreased, it recovered after keratectomy.

Tissue and cellular biomechanics during corneal wound injury and repair.

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Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P; Sermeno, Jasmyne; Reilly, Christopher M; Murphy, Christopher J

2017-08-01

thickness. Tissue biomechanics during the course of corneal wound healing is documented for the first time through atomic force microscopy, and is correlated with advanced clinical imaging and immunohistochemistry. Parameters obtained from the study are applied in a multivariate statistical model to cluster the data for better classification and monitor the wound repair process. Elastic modulus of the anterior corneal stroma is dramatically altered following wounding and correlates initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Importantly, the occurrence of myofibroblasts is preceded by changes in tissue mechanics, which is important to consider in light of crosslinking procedures applied to treat corneal diseases. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of silk fibroin in murine dry eye

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Kim, Chae Eun; Lee, Ji Hyun; Yeon, Yeung Kyu; Park, Chan Hum; Yang, Jaewook

2017-03-01

The study aimed to investigate the effects of silk fibroin in a mouse model of dry eye. The experimental dry eye mouse model was developed using more than twelve-weeks-old NOD.B10.H2b mice exposing them to 30-40% ambient humidity and injecting them with scopolamine hydrobromide for 10 days. Tear production and corneal irregularity score were measured by the instillation of phosphate buffered saline or silk fibroin. Corneal detachment and conjunctival goblet cell density were observed by hematoxylin and eosin or periodic acid Schiff staining in the cornea or conjunctiva. The expression of inflammatory markers was detected by immunohistochemistry in the lacrimal gland. The silk group tear production was increased, and corneal smoothness was improved. The corneal epithelial cells and conjunctival goblet cells were recovered in the silk groups. The expression of inflammatory factors was inhibited in the lacrimal gland of the silk group. These results show that silk fibroin improved the cornea, conjunctiva, and lacrimal gland in the mouse model of dry eye. These findings suggest that silk fibroin has anti-inflammatory effects in the experimental models of dry eye.

Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery.

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Anitua, E; Muruzabal, F; Alcalde, I; Merayo-Lloves, J; Orive, G

2013-10-01

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Establishment of a new in vitro test method for evaluation of eye irritancy using a reconstructed human corneal epithelial model, LabCyte CORNEA-MODEL.

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Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-ichiro

2013-12-01

Finding in vitro eye irritation testing alternatives to animal testing such as the Draize eye test, which uses rabbits, is essential from the standpoint of animal welfare. It has been developed a reconstructed human corneal epithelial model, the LabCyte CORNEA-MODEL, which has a representative corneal epithelium-like structure. Protocol optimization (pre-validation study) was examined in order to establish a new alternative method for eye irritancy evaluation with this model. From the results of the optimization experiments, the application periods for chemicals were set at 1min for liquid chemicals or 24h for solid chemicals, and the post-exposure incubation periods were set at 24h for liquids or zero for solids. If the viability was less than 50%, the chemical was judged to be an eye irritant. Sixty-one chemicals were applied in the optimized protocol using the LabCyte CORNEA-MODEL and these results were evaluated in correlation with in vivo results. The predictions of the optimized LabCyte CORNEA-MODEL eye irritation test methods were highly correlated with in vivo eye irritation (sensitivity 100%, specificity 80.0%, and accuracy 91.8%). These results suggest that the LabCyte CORNEA-MODEL eye irritation test could be useful as an alternative method to the Draize eye test. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of two different incision phacoemulsification on corneal astigmatism

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Lu Huo

2014-12-01

Full Text Available AIM:To compare the effect of different incision in corneal astigmatism after phacoemulsification. METHODS: Totally 88 cases(122 eyeswith pure cataract were randomly divided into two groups. Forty cases(60 eyeswere clarity corneal incision in group A, and 48 cases(62 eyeswere sclera tunnel incision in group B. Mean corneal astigmatism, surgically induced astigmatism(SIA, uncorrected visual acuity(UCVAand best correct vision acuity(BCVAwere observed in pre- and post-operation at 1d; 1wk; 1mo.RESULTS: The mean astigmatism had statistically significant difference between two groups at 1d; 1wk; 1mo after operation(PPP>0.05. UCVA≥0.5 and BCVA≥0.8 had statistically significant difference at 1d; 1wk(PP>0.05.CONCLUSION: Phacoemulsification with scleral tunnel incision remove combined intraocular lens(IOLimplantation has small changes to corneal astigmatism. By selecting personalized corneal incision according to the corneal topography might be more beneficial.

Comparison of postoperative corneal changes between dry eye and non-dry eye in a murine cataract surgery model

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Kwon, Jin Woo; Chung, Yeon Woong; Choi, Jin A; La, Tae Yoon; Jee, Dong Hyun; Cho, Yang Kyung

2016-01-01

AIM To compare the effects of the surgical insult of cataract surgery on corneal inflammatory infiltration, neovascularization (NV) and lymphangiogenesis (LY) between the dry eye and non-dry eye in murine cataract surgery models. METHODS We established two groups of animals, one with normal eyes (non-dry eye) and the second with induced dry eyes. In both groups, we used surgical insults to mimic human cataract surgery, which consisted of lens extraction, corneal incision and suture. After harvesting of corneas on the 9th postoperative day and immunohistochemical staining, we compared NV, LY and CD11b+ cell infiltration in the corneas. RESULTS Dry eye group had significantly more inflammatory infiltration (21.75%±7.17% vs 3.65%±1.49%; P=0.049). The dry eye group showed significantly more NV (48.21%±4.02% vs 26.24%±6.01%; P=0.016) and greater levels of LY (9.27%±0.48% vs 4.84%±1.15%; P=0.007). In corneas on which no surgery was performed, there was no induction of NV in both the dry and non-dry group, but dry eye group demonstrated more CD11b+ cells infiltration than the non-dry eye group (0.360%±0.160% vs 0.023%±0.006%; P=0.068). Dry eye group showed more NV than non-dry eye group in both topical PBS application and subconjunctival PBS injection (P=0.020 and 0.000, respectively). CONCLUSION In a murine cataract surgery model, preexisting dry eye can induce more postoperative NV, LY, and inflammation in corneal tissue. PMID:26949638

Airbag induced corneal ectasia.

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Mearza, Ali A; Koufaki, Fedra N; Aslanides, Ioannis M

2008-02-01

To report a case of airbag induced corneal ectasia. Case report. A patient 3 years post-LASIK developed bilateral corneal ectasia worse in the right eye following airbag deployment in a road traffic accident. At last follow up, best corrected vision was 20/40 with -4.00/-4.00 x 25 in the right eye and 20/25 with -1.25/-0.50 x 135 in the left eye. This is a rare presentation of trauma induced ectasia in a patient post-LASIK. It is possible that reduction in biomechanical integrity of the cornea from prior refractive surgery contributed to this presentation.

Changes in corneal endothelial cell density and the cumulative risk of corneal decompensation after Ahmed glaucoma valve implantation.

Science.gov (United States)

Kim, Kyoung Nam; Lee, Sung Bok; Lee, Yeon Hee; Lee, Jong Joo; Lim, Hyung Bin; Kim, Chang-Sik

2016-07-01

To evaluate changes in the corneal endothelial cell density (ECD) and corneal decompensation following Ahmed glaucoma valve (AGV) implantation. This study was retrospective and observational case series. Patients with refractory glaucoma who underwent AGV implantation and were followed >5 years were consecutively enrolled. We reviewed the medical records, including the results of central corneal specular microscopy. Of the 127 enrolled patients, the annual change in ECD (%) was determined using linear regression for 72 eyes evaluated at least four times using serial specular microscopic examination and compared with 31 control eyes (fellow glaucomatous eyes under medical treatment). The main outcome measures were cumulative risk of corneal decompensation and differences in the ECD loss rates between subjects and controls. The mean follow-up after AGV implantation was 43.1 months. There were no cases of postoperative tube-corneal touch. The cumulative risk of corneal decompensation was 3.3%, 5 years after AGV implantation. There was a more rapid loss of ECD in the 72 subject eyes compared with the 31 controls (-7.0% and -0.1%/year, respectively; p<0.001). However, the rate of loss decreased over time and statistical significance compared with control eyes disappeared after 2 years postoperatively: -10.7% from baseline to 1 year (p<0.01), -7.0% from 1 year to 2 years (p=0.037), -4.2% from 2 years to 3 years (p=0.230) and -2.7% from 3 years to the final follow-up (p=0.111). In case of uncomplicated AGV implantation, the cumulative risk of corneal decompensation was 3.3%, 5 years after the operation. The ECD loss was statistically greater in eyes with AGV than in control eyes without AGV, but the difference was significant only up to 2 years post surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Role of Decorin Core Protein in Collagen Organisation in Congenital Stromal Corneal Dystrophy (CSCD.

Directory of Open Access Journals (Sweden)

Christina S Kamma-Lorger

Full Text Available The role of Decorin in organising the extracellular matrix was examined in normal human corneas and in corneas from patients with Congenital Stromal Corneal Dystrophy (CSCD. In CSCD, corneal clouding occurs due to a truncating mutation (c.967delT in the decorin (DCN gene. Normal human Decorin protein and the truncated one were reconstructed in silico using homology modelling techniques to explore structural changes in the diseased protein. Corneal CSCD specimens were also examined using 3-D electron tomography and Small Angle X-ray diffraction (SAXS, to image the collagen-proteoglycan arrangement and to quantify fibrillar diameters, respectively. Homology modelling showed that truncated Decorin had a different spatial geometry to the normal one, with the truncation removing a major part of the site that interacts with collagen, compromising its ability to bind effectively. Electron tomography showed regions of abnormal stroma, where collagen fibrils came together to form thicker fibrillar structures, showing that Decorin plays a key role in the maintenance of the order in the normal corneal extracellular matrix. Average diameter of individual fibrils throughout the thickness of the cornea however remained normal.

Corneal manifestations in systemic diseases

OpenAIRE

Zarranz-Ventura, J.; Nova, E. De; Moreno-Montañés, J.

2008-01-01

Un gran número de enfermedades sistémicas presentan manifestaciones corneales dentro de su espectro de enfermedad. El estudio detallado de todos los cuadros que asocian patología corneal resulta inabarcable, por ello se presentan las enfermedades más prevalentes o características. Este estudio contempla las enfermedades pulmonares y conectivopatías (colagenosis, enfermedades reumatológicas y enfermedades inflamatorias idiopáticas), las enfermedades dermatológicas, cardiovasculares, hematológi...

Acute corneal hydrops in keratoconus

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Prafulla K Maharana

2013-01-01

Full Text Available Acute corneal hydrops is a condition characterized by stromal edema due to leakage of aqueous through a tear in descemet membrane. The patient presents with sudden onset decrease in vision, photophobia, and pain. Corneal thinning and ectasias combined with trivial trauma to the eye mostly by eye rubbing is considered as the underlying cause. With conservative approach self-resolution takes around 2 to 3 months. Surgical intervention is required in cases of non-resolution of corneal edema to avoid complications and for early visual rehabilitation. Intracameral injection of air or gas such as perflouropropane is the most common surgical procedure done. Recent investigative modality such as anterior segment optical coherence tomography is an extremely useful tool for diagnosis, surgical planning, and postoperative follow up. Resolution of hydrops may improve the contact lens tolerance and visual acuity but most cases require keratoplasty for visual rehabilitation.

Spontaneous Healing of Corneal Perforation after Temporary Discontinuation of Erlotinib Treatment

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Naoyuki Morishige

2014-01-01

Full Text Available Purpose: To report a case of corneal perforation associated with oral administration of erlotinib and its spontaneous healing after temporary discontinuation of drug treatment. Case Report: A 65-year-old man with metastatic lung cancer was treated with erlotinib (150 mg/day, a specific tyrosine kinase inhibitor of the epidermal growth factor receptor. He was referred to our corneal service for the treatment of bilateral corneal disorders, diagnosed with mild aqueous-deficient dry eye, and treated by insertion of punctal plugs. His corneal epithelial disorders initially improved, but subsequently worsened, as manifested by the development of bilateral corneal ulceration with corneal perforation in the right eye. The oral administration of erlotinib was interrupted in preparation for tectonic keratoplasty, but 2 days later the corneal perforation of the right eye and the bilateral epithelial defects had healed spontaneously. Treatment with erlotinib was resumed at half the initial dose, and the cornea of both eyes has remained apparently healthy. Discussion: Erlotinib may be secreted into tear fluid and thereby adversely affect the corneal epithelium. The development of corneal epithelial disorders in patients receiving this drug may be reversed by reducing its dose.

Management of corneal bee sting

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Razmjoo H

2011-12-01

Full Text Available Hassan Razmjoo1,2, Mohammad-Ali Abtahi1,2,4, Peyman Roomizadeh1,3, Zahra Mohammadi1,2, Seyed-Hossein Abtahi1,3,41Medical School, Isfahan University of Medical Sciences (IUMS; 2Ophthalmology Ward, Feiz Hospital, IUMS; 3Isfahan Medical Students Research Center (IMSRC, IUMS; 4Isfahan Ophthalmology Research Center (IORC, Feiz Hospital, IUMS, Isfahan, IranAbstract: Corneal bee sting is an uncommon environmental eye injury that can result in various ocular complications with an etiology of penetrating, immunologic, and toxic effects of the stinger and its injected venom. In this study we present our experience in the management of a middle-aged male with a right-sided deep corneal bee sting. On arrival, the patient was complaining of severe pain, blurry vision with acuity of 160/200, and tearing, which he had experienced soon after the injury. Firstly, we administered conventional drugs for eye injuries, including topical antibiotic, corticosteroid, and cycloplegic agents. After 2 days, corneal stromal infiltration and edema developed around the site of the sting, and visual acuity decreased to 100/200. These conditions led us to remove the stinger surgically. Within 25 days of follow-up, the corneal infiltration decreased gradually, and visual acuity improved to 180/200. We suggest a two-stage management approach for cases of corneal sting. For the first stage, if the stinger is readily accessible or primary dramatic reactions, including infiltration, especially on the visual axis, exist, manual or surgical removal would be indicated. Otherwise, we recommend conventional treatments for eye injuries. Given this situation, patients should be closely monitored for detection of any worsening. If the condition does not resolve or even deteriorates, for the second stage, surgical removal of the stinger under local or generalized anesthesia is indicated.Keywords: bee sting, stinger, cornea, removal, management, surgery

Molecular mechanism of ocular surface damage: application to an in vitro dry eye model on human corneal epithelium.

Science.gov (United States)

Meloni, Marisa; De Servi, Barbara; Marasco, Daniela; Del Prete, Salvatore

2011-01-12

The present study was concerned with the development of a new experimental model of dry eye using human reconstructed in vitro corneal epithelium (HCE). The model is based on the use of adapted culture conditions that induce relevant modifications at the cellular and molecular level thus mimicking dry eye. The HCE model was maintained in a controlled environmental setting (relative humidity eye. The evolution of the dry eye condition was assessed by histology, immunohistochemistry staining, scanning electron microscopy, and gene expression by using TaqMan gene assay technology (mucin-4 [MUC4], matrix metallopeptidase-9 [MMP9], tumor necrosis factor-α [TNF-α], and defensin β-2 [DEFB2). The effects of different commercially available tear substitutes on the induced dry eye condition were tested. This in vitro dry eye HCE model, that was well established within 24 h, has the characteristic features of a dry eye epithelium and could be satisfactorily used for preliminary assessment of the protective activity of some artificial tears. The transcriptional study of selected biomarkers showed an increase in MUC4, MMP9, TNF-α, and hBD-2 (DEFB2) gene expression. By using a dynamic approach, we were able to define a biomarker gene signature of dry eye-induced effects that could be predictive of corneal damage in vivo and to discriminate the efficacy among different commercial artificial tears.

Impact of Facial Conformation on Canine Health: Corneal Ulceration

Science.gov (United States)

Packer, Rowena M. A.; Hendricks, Anke; Burn, Charlotte C.

2015-01-01

Concern has arisen in recent years that selection for extreme facial morphology in the domestic dog may be leading to an increased frequency of eye disorders. Corneal ulcers are a common and painful eye problem in domestic dogs that can lead to scarring and/or perforation of the cornea, potentially causing blindness. Exaggerated juvenile-like craniofacial conformations and wide eyes have been suspected as risk factors for corneal ulceration. This study aimed to quantify the relationship between corneal ulceration risk and conformational factors including relative eyelid aperture width, brachycephalic (short-muzzled) skull shape, the presence of a nasal fold (wrinkle), and exposed eye-white. A 14 month cross-sectional study of dogs entering a large UK based small animal referral hospital for both corneal ulcers and unrelated disorders was carried out. Dogs were classed as affected if they were diagnosed with a corneal ulcer using fluorescein dye while at the hospital (whether referred for this disorder or not), or if a previous diagnosis of corneal ulcer(s) was documented in the dogs’ histories. Of 700 dogs recruited, measured and clinically examined, 31 were affected by corneal ulcers. Most cases were male (71%), small breed dogs (mean± SE weight: 11.4±1.1 kg), with the most commonly diagnosed breed being the Pug. Dogs with nasal folds were nearly five times more likely to be affected by corneal ulcers than those without, and brachycephalic dogs (craniofacial ratio dogs. A 10% increase in relative eyelid aperture width more than tripled the ulcer risk. Exposed eye-white was associated with a nearly three times increased risk. The results demonstrate that artificially selecting for these facial characteristics greatly heightens the risk of corneal ulcers, and such selection should thus be discouraged to improve canine welfare. PMID:25969983

Crosslinking and corneal cryotherapy in acanthamoeba keratitis -- a histological study.

Science.gov (United States)

Hager, Tobias; Hasenfus, A; Stachon, T; Seitz, B; Szentmáry, N

2016-01-01

Acanthamoeba keratitis is rare, but difficult to treat. Penetrating keratoplasty is performed in therapy-resistant cases. Nevertheless, subsequent recurrences occur in 40 % of the cases. In addition to triple-topical therapy (polyhexamid, propamidinisoethionat, neomycin), treatment alternatives are corneal cryotherapy and/or crosslinking (CXL). The aim of our present histological study was to analyze the persistence of acanthamoebatrophozoites and cysts, the persistence of bacteria, and activation of keratocytes in corneas of acanthamoeba keratitis patients following corneal cryotherapy and/or CXL. We analyzed histologically corneal buttons (from penetrating keratoplasties) of nine patients with acanthamoeba keratitis, following corneal cryotherapy (two patients) or a combination of crosslinking and corneal cryotherapy (seven patients), using haematoxilin–eosin, periodic acid Schiff (PAS), Gram and alpha-smooth muscle actin (alpha-SMA) stainings. Acanthamoeba trophozoites persisted in three corneas after cryotherapy and CXL. Cysts persisted in one of two corneas following corneal cryotherapy and in six of seven corneas after a combination of CXL and cryotherapy. One cornea showed positive Gram staining, but there were no alpha-SMA positive keratocytes in any of the corneas. Crosslinking and corneal cryotherapy have only limited impact on killing of acanthamoeba trophozoites, cysts, or bacteria. Corneal cryotherapy and CXL did not stimulate myofibroblastic transformation of keratocytes.

Corneal topography

DEFF Research Database (Denmark)

Andersen, J.; Koch-Jensen, P.; Østerby, Ole

1993-01-01

The central corneal zone is depicted on keratoscope photographs using a small target aperture and a large object distance. Information on the peripheral area is included by employing a hemispherical target with a dense circular and radial pattern. On a 16 mm (R = 8 mm) reference steel sphere the ...

Prevalence and associated factors of corneal blindness in Ningxia in northwest China

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Xun-Lun Sheng

2014-06-01

Full Text Available AIM:To describe the prevalence and demographic characteristics of corneal blindness in an urban and rural region of Ningxia, located in the northwest part of China.METHODS:A stratified, randomized sampling procedure was employed in the study, including urban and rural area of all age group. Visual acuity, anterior segment and ocular fundus were checked. Related factor of corneal disease, including age, gender, education status, ethnic group, location and occupation, were identified according to uniform customized protocol. An eye was defined to be corneal blindness if the visual acuity was <20/400 due to a corneal disease.RESULTS:Three thousand individuals (1290 from urban area and 1710 from rural area participated in the investigation, with a response rate of 80.380%. The prevalence of corneal blindness was 0.023% in both eyes and 0.733% in at least one eye. The blindness in at least one eye with varied causes was present in 106 participants (3.533% and in bilateral eyes in 34 participants (1.133%. The corneal diseases accounted for 20.754% of blindness in at least one eye and 20.588% of bilateral blindness. The prevalence of corneal disease was higher in older and Han ethnic group, especially those who occupied in agriculture and outdoor work. People with corneal blindness were more likely to be older and lower education. Rural population were more likely to suffer from bilateral corneal blindness than the urban population in ≥59-year group (χ2=6.716, P=0.019. Infectious, trauma and immune corneal disease were the three leading causes of corneal disease. Trauma corneal disease was more likely leading to blindness in one eye. However, infectious and immune corneal diseases make more contribution to the bilateral corneal blindness.CONCLUSION: Corneal blindness is a significant burden of in Ningxia population, encompassing a variety of corneal infections and trauma; the majority of those were avoidable. Health promotion strategies and good

Human cadaver retina model for retinal heating during corneal surgery with a femtosecond laser

Science.gov (United States)

Sun, Hui; Fan, Zhongwei; Yun, Jin; Zhao, Tianzhuo; Yan, Ying; Kurtz, Ron M.; Juhasz, Tibor

2014-02-01

Femtosecond lasers are widely used in everyday clinical procedures to perform minimally invasive corneal refractive surgery. The intralase femtosecond laser (AMO Corp. Santa Ana, CA) is a common example of such a laser. In the present study a numerical simulation was developed to quantify the temperature rise in the retina during femtosecond intracorneal surgery. Also, ex-vivo retinal heating due to laser irradiation was measured with an infrared thermal camera (Fluke Corp. Everett, WA) as a validation of the simulation. A computer simulation was developed using Comsol Multiphysics to calculate the temperature rise in the cadaver retina during femtosecond laser corneal surgery. The simulation showed a temperature rise of less than 0.3 degrees for realistic pulse energies for the various repetition rates. Human cadaver retinas were irradiated with a 150 kHz Intralase femtosecond laser and the temperature rise was measured withan infrared thermal camera. Thermal camera measurements are in agreement with the simulation. During routine femtosecond laser corneal surgery with normal clinical parameters, the temperature rise is well beneath the threshold for retina damage. The simulation predictions are in agreement with thermal measurements providing a level of experimental validation.

Proteomic Analyses of the Acute Tissue Response for Explant Rabbit Corneas and Engineered Corneal Tissue Models Following In Vitro Exposure to 1540 nm Laser Light

National Research Council Canada - National Science Library

Eurell, T. E; Johnson, T. E; Roach, W. P

2005-01-01

Two-dimensional electrophoresis and histomorphometry were used to determine if equivalent protein changes occurred within native rabbit corneas and engineered corneal tissue models following in vitro...

Corneal Biomechanical Properties after FS-LASIK with Residual Bed Thickness Less Than 50% of the Original Corneal Thickness

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Haixia Zhang

2018-01-01

Full Text Available Background. The changes in corneal biomechanical properties after LASIK remain an unknown but important topic for surgical design and prognostic evaluation. This study aims to observe the postoperative corneal biomechanical properties one month after LASIK with amount of corneal cutting (ACC greater than 50% of the central corneal thickness (CCT. Methods. FS-LASIK was performed in 10 left rabbit eyes with ACC being 60% (L60 and 65% (L65 of the CCT, while the right eyes (R were the control. After 4 weeks, rabbits were executed and corneal strip samples were prepared for uniaxial tensile tests. Results. At the same strain, the stresses of L65 and L60 were larger than those of R. The elastic moduli of L60 and L65 were larger than those of R when the stress was 0.02 MPa, while they began to be less than those of R when stress exceeds the low-stress region. After 10 s relaxation, the stress of specimens L65, L60, and R increased in turn. Conclusion. The elastic moduli of the cornea after FS-LASIK with ACC greater than 50% of the CCT do not become less under normal rabbit IOP. The limit stress grows with the rise of ACC when relaxation becomes stable.

Temporary corneal stem cell dysfunction after radiation therapy

International Nuclear Information System (INIS)

Hiroshi, Fujishima; Kazuo, Tsubota

1996-01-01

Radiation therapy can cause corneal and conjuctival abnormalities that sometimes require surgical treatment. Corneal stem cell dysfunction is described, which recovered after the cessation of radiation. Methods - A 44-year-old man developed a corneal epithelial abnormality associated with conjuctival and corneal inflammation following radiation therapy for maxillary cancer. Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes. Impression cytology showed goblet cells in the same part of the cornea. Specular microscopy revealed spindle type epithelial cells. Patient follow up included artificial tears and an antibiotic ophthalmic ointment. The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation. Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea. Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery. (Author)

The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing.

Science.gov (United States)

Couture, Camille; Zaniolo, Karine; Carrier, Patrick; Lake, Jennifer; Patenaude, Julien; Germain, Lucie; Guérin, Sylvain L

2016-02-01

Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experimental photoallergic contact dermatitis: a mouse model

International Nuclear Information System (INIS)

Maguire, H.C. Jr.; Kaidbey, K.

1982-01-01

We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model

Effects of Silicone Hydrogel Contact Lens Application on Corneal High-order Aberration and Visual Guality in Patients with Corneal Opacities

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Sevda Aydın Kurna

2012-03-01

Full Text Available Pur po se: Evaluation of the corneal high-order aberrations and visual quality changes after application of silicone hydrogel contact lenses in patients with corneal opacities due to various etiologies. Ma te ri al and Met hod: Fifteen eyes of 13 patients with corneal opacities were included in the study. During the ophthalmologic examination before and after contact lens application, visual acuity was measured with Snellen acuity chart and contrast sensitivity - with Bailey-Lowie Charts in letters. Aberrations were measured with corneal aberrometer (NIDEK Magellan Mapper under a naturally dilated pupil. Spherical aberration, coma, trefoil, irregular astigmatism and total high-order root mean square (RMS values were recorded. Measurements were repeated with balafilcon A lenses (PureVision 2 HD, B&L on all patients. Re sults: Patient age varied between 23 and 50 years. Two eyes had subepithelial infiltrates due to adenoviral keratitis, 1 had nebulae due to previous infections or trauma, and 2 had Salzmann’s nodular degeneration. We observed a mean increase of 1 line in visual acuity and 5 letters in contrast sensitivity with contact lenses versus glasses in the patients. Mean RMS values of spherical aberration, irregular astigmatism and total high-order aberrations decreased significantly with contact lenses. Dis cus si on: Silicone hydrogel soft contact lenses may improve visual quality by decreasing the corneal aberrations in patients with corneal opacities. (Turk J Ophthalmol 2012; 42: 97-102

Transgenic mouse models of hormonal mammary carcinogenesis: advantages and limitations.

Science.gov (United States)

Kirma, Nameer B; Tekmal, Rajeshwar R

2012-09-01

Mouse models of breast cancer, especially transgenic and knockout mice, have been established as valuable tools in shedding light on factors involved in preneoplastic changes, tumor development and malignant progression. The majority of mouse transgenic models develop estrogen receptor (ER) negative tumors. This is seen as a drawback because the majority of human breast cancers present an ER positive phenotype. On the other hand, several transgenic mouse models have been developed that produce ER positive mammary tumors. These include mice over-expressing aromatase, ERα, PELP-1 and AIB-1. In this review, we will discuss the value of these models as physiologically relevant in vivo systems to understand breast cancer as well as some of the pitfalls involving these models. In all, we argue that the use of transgenic models has improved our understanding of the molecular aspects and biology of breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Altered corneal biomechanical properties in children with osteogenesis imperfecta.

Science.gov (United States)

Lagrou, Lisa M; Gilbert, Jesse; Hannibal, Mark; Caird, Michelle S; Thomas, Inas; Moroi, Sayoko E; Bohnsack, Brenda L

2018-04-07

To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI). A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test. A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg). Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Regulation of corneal stroma extracellular matrix assembly.

Science.gov (United States)

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dextran Preserves Native Corneal Structure During Decellularization.

Science.gov (United States)

Lynch, Amy P; Wilson, Samantha L; Ahearne, Mark

2016-06-01

Corneal decellularization has become an increasingly popular technique for generating scaffolds for corneal regeneration. Most decellularization procedures result in tissue swelling, thus limiting their application. Here, the use of a polysaccharide, dextran, to reduce swelling and conserve the native corneal structure during decellularization was investigated. Corneas were treated with 1% Triton X-100, 0.5% sodium dodecyl sulfate, and nucleases under constant rotation followed by extensive washing. To reduce swelling, decellularization solutions were supplemented with 5% dextran either throughout the whole decellularization process or during the washing cycles only. Quantitative analysis of DNA content showed a 96% reduction after decellularization regardless of the addition of dextran. Dextran resulted in a significant reduction in swelling from 3.85 ± 0.43 nm without to 1.94 ± 0.29-2.01 ± 0.37 nm (p dextran must be present throughout the decellularization protocol to preserve the native corneal architecture, anisotropy analysis demonstrated comparable results (0.22 ± 0.03) to the native cornea (0.24 ± 0.02), p > 0.05. Dextran can counteract the detrimental effects of decellularizing agents on the biomechanical properties of the tissue resulting in similar compressive moduli (mean before decellularization: 5.40 ± 1.18 kPa; mean after decellularization with dextran: 5.64 ± 1.34 kPa, p > 0.05). Cells remained viable in the presence of decellularized scaffolds. The findings of this study indicate that dextran not only prevents significant corneal swelling during decellularization but also enhances the maintenance of the native corneal ultrastructure.

Comparison of the Keratometric Corneal Astigmatic Power after Phacoemulsification: Clear Temporal Corneal Incision versus Superior Scleral Tunnel Incision

Directory of Open Access Journals (Sweden)

Yongqi He

2009-01-01

Full Text Available Objective. This is prospective randomized control trial to compare the mean keratometric corneal astigmatism diopter power (not surgical induced astigmatism among preop and one-month and three-month postop phacoemulcification of either a clear temporal corneal incision or a superior scleral tunnel Incision, using only keratometric astigmatic power reading to evaluate the difference between the two cataract surgery incisions. Methods. 120 patients (134 eyes underwent phacoemulcification were randomly assigned to two groups: Group A, the clear temporal corneal incision group, and Group B, the superior scleral tunnel incision group. SPSS11.5 Software was used for statistical analysis to compare the postsurgical changes of cornea astigmatism on keratometry. Results. The changes of corneal astigmatic diopter in Groups A and B after 3 month postop from keratometric reading were 1.04 + 0.76 and 0.94 + 0.27, respectively (=.84>.05, which showed no statistic significance difference. Conclusion. The incision through either temporal clear cornea or superior scleral tunnel in phacoemulcification shows no statistic difference in astigmatism change on keratometry 3-month postop.

Analysis of corneal topography in patients with pure microphthalmia in Eastern China.

Science.gov (United States)

Hu, Pei-Hong; Gao, Gui-Ping; Yu, Yao; Pei, Chong-Gang; Zhou, Qiong; Huang, Xin; Zhang, Ying; Shao, Yi

2015-12-01

To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. © The Author(s) 2015.

Small-Molecule Induction Promotes Corneal Epithelial Cell Differentiation from Human Induced Pluripotent Stem Cells

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Alexandra Mikhailova

2014-02-01

Full Text Available Human induced pluripotent stem cells (hiPSCs offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

Congenital Corneal Anesthesia and Neurotrophic Keratitis: Diagnosis and Management

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Flavio Mantelli

2015-01-01

Full Text Available Neurotrophic keratitis (NK is a rare degenerative disease of the cornea caused by an impairment of corneal sensory innervation, characterized by decreased or absent corneal sensitivity resulting in epithelial keratopathy, ulceration, and perforation. The aetiopathogenesis of corneal sensory innervation impairment in children recognizes the same range of causes as adults, although they are much less frequent in the pediatric population. Some extremely rare congenital diseases could be considered in the aetiopathogenesis of NK in children. Congenital corneal anesthesia is an extremely rare condition that carries considerable diagnostic and therapeutic problems. Typically the onset is up to 3 years of age and the cornea may be affected in isolation or the sensory deficit may exist as a component of a congenital syndrome, or it may be associated with systemic somatic anomalies. Accurate diagnosis and recognition of risk factors is important for lessening long-term sequelae of this condition. Treatment should include frequent topical lubrication and bandage corneal or scleral contact lenses. Surgery may be needed in refractory cases. The purpose of this review is to summarize and update data available on congenital causes and treatment of corneal hypo/anesthesia and, in turn, on congenital NK.

Analysis of corneal esthesia in patients undergoing photorefractive keratectomy

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Elmar Torres Neto

2015-12-01

Full Text Available ABSTRACT Purpose: To quantitatively analyze corneal esthesia in patients undergoing photorefractive keratectomy (PRK surgery. Methods: Forty-five patients selected for PRK in one eye underwent corneal esthesia using a Cochet-Bonnet esthesiometer preoperatively and 30 and 90 days postoperatively. Patients with a refractive diopter error of 4 or greater received intraoperative 0.02% mitomycin C for 20 s. Results: Twenty-four (53.3% of the 45 eyes received intraoperative 0.02% mitomycin. Decreased sensitivity was observed on postoperative day 30. By postoperative day 90, corneal esthesia had normalized but remained 14.9% lower than preoperative levels. In the mitomycin group, no recovery of corneal esthesia to normal sensitivity levels was observed. The mean esthesiometer level was 39.2 mm on postoperative day 90 (P<0.001. Conclusions: The results of the present study demonstrate recovery of corneal esthesia to normal levels at 90 days postoperatively in patients who did not receive mitomycin C. In patients administered mitomycin C, a 23.59% reduction in the corneal touch threshold was observed compared with preoperative levels indicating a failure of recovery to normal levels.

Corneal conjunctivalization management with high Dk RGP contact lenses.

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Martin, Raul

2009-06-01

To describe the management of corneal conjunctivalization with a high Dk RGP contact lens (CL) fitting. A high Dk RGP CL (Menicon Z-alpha Dk=189, Japan) was fitted, after temporary suspension of CL wear (6 months and 3 weeks), in two patients (a 36-year-old female and a 38-year-old male) who had corneal conjunctivalization secondary to low Dk soft CL wear. Both patients had worn their soft CLs 12-14 h per day without symptoms for the previous 18-20 years. After 9-15 months of high Dk RGP wear, all signs of corneal conjunctivalization had disappeared (corneal vascularization, late fluorescein stain, etc.) and patients wore their RGP CL comfortably. Corneal conjunctivalization was resolved with non-invasive procedures (temporary discontinuation, preservative-free artificial tears and high Dk RGP CL fitting) and thus other treatments (topical or surgical treatments such as limbus transplantation, amniotic membrane transplant or others) were not necessary. Short temporary suspension of CL wear (3 weeks), preservative-free artificial tears and refitting with high oxygen permeability RGP CL may be an alternative for the management of corneal conjunctivalization secondary to CL wear.

Bioactive self-assembled peptide nanofibers for corneal stroma regeneration.

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Uzunalli, G; Soran, Z; Erkal, T S; Dagdas, Y S; Dinc, E; Hondur, A M; Bilgihan, K; Aydin, B; Guler, M O; Tekinay, A B

2014-03-01

Defects in the corneal stroma caused by trauma or diseases such as macular corneal dystrophy and keratoconus can be detrimental for vision. Development of therapeutic methods to enhance corneal regeneration is essential for treatment of these defects. This paper describes a bioactive peptide nanofiber scaffold system for corneal tissue regeneration. These nanofibers are formed by self-assembling peptide amphiphile molecules containing laminin and fibronectin inspired sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide nanofibers retained their characteristic morphology, and their proliferation was enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide nanofibers increased keratocyte migration and supported stroma regeneration. These results suggest that laminin-mimetic peptide nanofibers provide a promising injectable, synthetic scaffold system for cornea stroma regeneration. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pirfenidone nanoparticles improve corneal wound healing and prevent scarring following alkali burn.

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Sushovan Chowdhury

Full Text Available To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn.Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide (PLGA nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry.Pirfenidone prevented (P<0.05 increase in TGF β induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05 reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn.Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases.

Corneal iron ring after hyperopic photorefractive keratectomy.

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Bilgihan, K; Akata, F; Gürelik, G; Adigüzel, U; Akpinar, M; Hasanreisoğlu, B

1999-05-01

To report the incidence and course of corneal iron deposition after hyperopic photorefractive keratectomy (PRK). Gazi University, Medical School, Department of Ophthalmology, Ankara, Turkey. Between January 1995 and December 1997, 62 eyes had PRK to correct hyperopia. Nine eyes developed corneal iron ring 5 to 8 months (mean 6.25 months +/- 1.3 [SD]) after PRK for hyperopia. The rings persisted during the mean follow-up of 19 +/- 11.09 months. The ring-shaped iron deposition after PRK for hyperopia must be differentiated from the Fleischer ring. Our results suggest that the slitlamp findings of peripheral corneal iron deposition in hyperopic PRK patients correlate with achieved correction.

Corneal collagen crosslinking for keratoconus. A review

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M. M. Bikbov

2014-10-01

Full Text Available Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns. Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity increase by 328.9 % (on average, temperature tolerance increase by 5�

[The status quo and expectation of corneal research in China].

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Shi, Weiyun; Xie, Lixin

2014-09-01

In China, corneal disease is currently the second leading cause of blindness. Severe donor shortage, insufficient technique supports and promotion, and the lack of corneal disease specialists due to poor systematic training are all urgent problems to be resolved. The last 5 years have witnessed a considerable progress in basic and clinical researches of corneal disease. Investigations on the pathogenesis and treatment of fungal keratitis have won an international reputation. Results from the study of corneal reconstruction with tissue-engineered and acellular matrix corneas have been tested in clinical trials with good preliminary performance. Moreover, the clinical researches of corneal refractive surgery have kept pace with the latest international progresses. However, Descemet's membrane endothelial keratoplasty needs further promotion, and the development and application of keratoprosthesis remains a blank. Although keratoprosthesis and corneal collagen cross-linking have been widely applied in Europe with satisfactory clinical efficacy, they are still under assessment by China Food and Drug Administration for approval of use.

Corynebacterium macginleyi isolated from a corneal ulcer

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Kathryn Ruoff

2010-02-01

Full Text Available We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT. To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

21 CFR 886.4070 - Powered corneal burr.

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2010-04-01

...) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4070 Powered corneal burr. (a) Identification. A powered corneal burr is an AC-powered or battery-powered device that is a motor and drilling tool intended to remove rust rings from the cornea of the eye. (b) Classification. Class I (general controls). When...

Comparative analysis of corneal morphological changes after transversal and torsional phacoemulsification through 2.2 mm corneal incision.

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Assaf, Ahmed; Roshdy, Maged Maher

2013-01-01

This paper compares and evaluates the corneal morphological changes occurring after cataract surgery through a 2.2 mm corneal incision. We use two platforms for comparison and evaluation, transversal and torsional phacoemulsification. This study includes 139 consecutive cataractous eyes (nuclear color 2-4, according to the Lens Opacities Classification System III [LOCSIII]) of 82 patients undergoing cataract surgery through a 2.2 mm corneal incision. Two different phacoemulsification platforms were used and assigned randomly: we used the WhiteStar Signature(®) system with the Ellips™ FX transversal continuous ultrasound (US) mode for group I (mean age: 65.33 ± 6.97 years), and we used the Infiniti(®) system with the OZil(®) Intelligent Phaco (IP) torsional US mode for group II (mean age: 64.02 ± 7.55 years). The corneal endothelium and pachymetry were evaluated preoperatively and at 1 month postoperatively. Incision size changes were also evaluated. All surgeries were uneventful. Before intraocular lens implantation, the mean incision size was 2.24 ± 0.06 mm in both groups (P = 0.75). In terms of corneal endothelial cell density, neither preoperative (I vs II: 2304.1 ± 122.5 cell/mm(2) vs 2315.6 ± 83.1 cell/mm(2), P = 0.80) nor postoperative (I vs II: 2264.1 ± 124.3 cell/mm(2) vs 2270.3 ± 89.9 cell/mm(2), P = 0.98) differences between the groups were statistically significant. The mean endothelial cell density loss was 1.7% ± 1.6% and 2.0% ± 1.4% in groups I and II, respectively. Furthermore, no significant differences between groups I and II were found preoperatively (P = 0.40) and postoperatively (P = 0.68) in central pachymetry. With surgery, the mean increase in central pachymetry was 28.1 ± 23.6 μm and 24.0 ± 24.0 μm in groups I and II, respectively (P = 0.1). Ellips™ FX transversal and OZil(®) IP torsional phacoemulsification modes are safe for performing cataract surgery, inducing minimal corneal thickness and endothelial changes.

The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis

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Wenjing Wu

2015-01-01

Full Text Available Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs after small incision lenticule extraction (SMILE and femtosecond laser in situ keratomileusis (FS-LASIK. Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH and the corneal resistance factor (CRF with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd–6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P<0.05, postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P<0.05. There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P=0.013. Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively.

Corneal graft reversal: Histopathologic report of two cases

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Qahtani, Abdullah A.; Alkatan, Hind M.

2014-01-01

Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for faile...

Contact lens rehabilitation following repaired corneal perforations

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Titiyal, Jeewan S; Sinha, Rajesh; Sharma, Namrata; Sreenivas, V; Vajpayee, Rasik B

2006-01-01

Background Visual outcome following repair of post-traumatic corneal perforation may not be optimal due to presence of irregular keratometric astigmatism. We performed a study to evaluate and compare rigid gas permeable contact lens and spectacles in visual rehabilitation following perforating corneal injuries. Method Eyes that had undergone repair for corneal perforating injuries with or without lens aspiration were fitted rigid gas permeable contact lenses. The fitting pattern and the improvement in visual acuity by contact lens over spectacle correction were noted. Results Forty eyes of 40 patients that had undergone surgical repair of posttraumatic corneal perforations were fitted rigid gas permeable contact lenses for visual rehabilitation. Twenty-four eyes (60%) required aphakic contact lenses. The best corrected visual acuity (BCVA) of ≥ 6/18 in the snellen's acuity chart was seen in 10 (25%) eyes with spectacle correction and 37 (92.5%) eyes with the use of contact lens (p < 0.001). The best-corrected visual acuity with spectacles was 0.20 ± 0.13 while the same with contact lens was 0.58 ± 0.26. All the patients showed an improvement of ≥ 2 lines over spectacles in the snellen's acuity chart with contact lens. Conclusion Rigid gas permeable contact lenses are better means of rehabilitation in eyes that have an irregular cornea due to scars caused by perforating corneal injuries. PMID:16536877

Indications for Corneal Transplantation at a Tertiary Referral Center in Tehran

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Mohammad Zare

2010-01-01

Full Text Available Purpose: To report the indications and techniques of corneal transplantation at a tertiary referral center in Tehran over a 3-year period. Methods: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran from March 2004 to March 2007 were reviewed to determine the indications and types of corneal transplantation. Results: During this period, 776 eyes of 756 patients (including 504 male subjects with mean age of 41.3±21.3 years underwent corneal transplantation. The most common indication was keratoconus (n=317, 40.8% followed by bullous keratopathy (n=90, 11.6%, non-herpetic corneal scars (n=62, 8.0%, infectious corneal ulcers (n=61, 7.9%, previously failed grafts (n=61, 7.9%, endothelial and stromal corneal dystrophies (n=28, 3.6%, and trachoma keratopathy (n=26, 3.3%. Other indications including Terrien′s marginal degeneration, post-LASIK keratectasia, trauma, chemical burns, and peripheral ulcerative keratitis constituted the rest of cases. Techniques of corneal transplantation included penetrating keratoplasty (n=607, 78.2%, deep anterior lamellar keratoplasty (n=108, 13.9%, conventional lamellar keratoplasty (n=44, 5.7%, automated lamellar therapeutic keratoplasty (n=8, 1.0%, and Descemet stripping endothelial keratoplasty (n=6, 0.8% in descending order. The remaining cases were endothelial keratoplasty and sclerokeratoplasty. Conclusion: In this study, keratoconus was the most common indication for penetrating keratoplasty which was the most prevalent technique of corneal transplantation. However, deep anterior lamellar keratoplasty is emerging as a growing alternative for corneal pathologies not involving the endothelium.

Accelerated Development of Supramolecular Corneal Stromal-Like Assemblies from Corneal Fibroblasts in the Presence of Macromolecular Crowders.

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Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

2015-07-01

Tissue engineering by self-assembly uses the cells' secretome as a regeneration template and biological factory of trophic factors. Despite the several advantages that have been witnessed in preclinical and clinical settings, the major obstacle for wide acceptance of this technology remains the tardy extracellular matrix formation. In this study, we assessed the influence of macromolecular crowding (MMC)/excluding volume effect, a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude, in human corneal fibroblast (HCF) culture. Our data indicate that the addition of negatively charged galactose derivative (carrageenan) in HCF culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, while maintaining physiological cell morphology and protein/gene expression. Gene analysis indicates that a glucose derivative (dextran sulfate) may drive corneal fibroblasts toward a myofibroblast lineage. Collectively, these results indicate that MMC may be suitable not only for clinical translation and commercialization of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

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Salek, Reza M.; Pears, Michael R. [University of Cambridge, Department of Biochemistry and Cambridge Systems Biology Centre (United Kingdom); Cooper, Jonathan D. [King' s College London, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry (United Kingdom); Mitchison, Hannah M. [Royal Free and University College Medical School, Department of Paediatrics and Child Health (United Kingdom); Pearce, David A. [Sanford School of Medicine of the University of South Dakota, Department of Pediatrics (United States); Mortishire-Smith, Russell J. [Johnson and Johnson PR and D (Belgium); Griffin, Julian L., E-mail: jlg40@mole.bio.cam.ac.uk [University of Cambridge, Department of Biochemistry and the Cambridge Systems Biology Centre (United Kingdom)

2011-04-15

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in {gamma}-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

International Nuclear Information System (INIS)

Salek, Reza M.; Pears, Michael R.; Cooper, Jonathan D.; Mitchison, Hannah M.; Pearce, David A.; Mortishire-Smith, Russell J.; Griffin, Julian L.

2011-01-01

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

A minimal model of epithelial tissue dynamics and its application to the corneal epithelium

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Henkes, Silke; Matoz-Fernandez, Daniel; Kostanjevec, Kaja; Coburn, Luke; Sknepnek, Rastko; Collinson, J. Martin; Martens, Kirsten

Epithelial cell sheets are characterized by a complex interplay of active drivers, including cell motility, cell division and extrusion. Here we construct a particle-based minimal model tissue with only division/death dynamics and show that it always corresponds to a liquid state with a single dynamic time scale set by the division rate, and that no glassy phase is possible. Building on this, we construct an in-silico model of the mammalian corneal epithelium as such a tissue confined to a hemisphere bordered by the limbal stem cell zone. With added cell motility dynamics we are able to explain the steady-state spiral migration on the cornea, including the central vortex defect, and quantitatively compare it to eyes obtained from mice that are X-inactivation mosaic for LacZ.

Analysis of excimer laser radiant exposure effect toward corneal ablation volume at LASIK procedure

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Adiati, Rima Fitria; Rini Rizki, Artha Bona; Kusumawardhani, Apriani; Setijono, Heru; Rahmadiansah, Andi

2016-11-01

LASIK (Laser Asissted In Situ Interlamelar Keratomilieusis) is a technique for correcting refractive disorders of the eye such as myopia and astigmatism using an excimer laser. This procedure use photoablation technique to decompose corneal tissues. Although preferred due to its efficiency, permanency, and accuracy, the inappropriate amount radiant exposure often cause side effects like under-over correction, irregular astigmatism and problems on surrounding tissues. In this study, the radiant exposure effect toward corneal ablation volume has been modelled through several processes. Data collecting results is laser data specifications with 193 nm wavelength, beam diameter of 0.065 - 0.65 cm, and fluence of 160 mJ/cm2. For the medical data, the myopia-astigmatism value, cornea size, corneal ablation thickness, and flap data are taken. The first modelling step is determining the laser diameter between 0.065 - 0.65 cm with 0.45 cm increment. The energy, power, and intensity of laser determined from laser beam area. Number of pulse and total energy is calculated before the radiant exposure of laser is obtained. Next is to determine the parameters influence the ablation volume. Regression method used to create the equation, and then the spot size is substituted to the model. The validation used is statistic correlation method to both experimental data and theory. By the model created, it is expected that any potential complications can be prevented during LASIK procedures. The recommendations can give the users clearer picture to determine the appropriate amount of radiant exposure with the corneal ablation volume necessary.

Comparison of Corneal Biomechanical Properties between Indian and Chinese Adults.

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Chua, Jacqueline; Nongpiur, Monisha E; Zhao, Wanting; Tham, Yih Chung; Gupta, Preeti; Sabanayagam, Charumathi; Aung, Tin; Wong, Tien Yin; Cheng, Ching-Yu

2017-09-01

To investigate the difference in corneal hysteresis (CH) and corneal resistance factor (CRF) between Indian and Chinese populations. Population-based cross-sectional study. Three hundred eighty-two Singaporean Indian persons and 764 Singaporean Chinese 50 years of age or older were included from the Singapore Indian Eye Study and Singapore Chinese Eye Study, respectively. Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The CH and CRF were measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY). Information on genetic ancestry was derived using principal component analysis. Linear regression models were used to investigate the association of CH and CRF with potential risk factors. Corneal hysteresis and CRF. After excluding participants with a history of intraocular surgery, a diagnosis of glaucoma suspect or glaucoma, refractive surgery, or presence of corneal abnormalities, CH and CRF readings were available for 382 Indian persons. For each Indian participant, 2 Chinese participants were selected and matched for age and gender (n = 764). There were no differences in the clinical measurements of CH (10.6±1.6 mmHg; P = 0.670) or CRF (10.3±1.7 mmHg; P = 0.103) between the ethnic groups. However, after adjusting for covariates, Indian persons had, on average, 0.18-mmHg higher CH levels than in Chinese (95% confidence interval [CI], 0.02-0.38; P = 0.031). Consistently, CH level was correlated significantly with genetic ancestry in the Southeast Asian population. Corneal resistance factor level was not associated independently with self-reported ethnicity (95% CI, -0.10 to 0.29; P = 0.335). Chinese have lower CH than Indian persons, and this disparity may reflect biomechanical differences of the cornea. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical correlates of common corneal neovascular diseases:a literature review

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Nizar Saleh Abdelfattah

2015-02-01

Full Text Available A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization, leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far.

The Steroids for Corneal Ulcers Trial

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Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi; Ravindran, Meenakshi; Lalitha, Prajna; Glidden, David V.; Ray, Kathryn J.; Hong, Kevin C.; Oldenburg, Catherine E.; Lee, Salena M.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

2013-01-01

Objectives To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbio-logical results, and patient demographics, for patients enrolled in the trial. Results Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%). Conclusions The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. PMID:21987581

Corneal graft reversal: Histopathologic report of two cases.

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Qahtani, Abdullah A; Alkatan, Hind M

2014-10-01

Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for failed penetrating keratoplasty (PKP) which is donor graft reversal.

Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.

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Karpinski, Lorraine G; Miller, Christine L

2002-09-01

A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with bilateral corneal papillomas was serially immobilized and given subconjunctival injections of fluorouracil. Over the course of 17 weeks five bilateral injections of 25 mg fluorouracil were given. This treatment caused regression of the corneal lesions as evidenced by decreased lesion diameter, decreased corneal vascularity, increased corneal clarity, and improved visual function. No adverse drug effects were observed.

Differential expression of the Slc4 bicarbonate transporter family in murine corneal endothelium and cell culture.

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Shei, William; Liu, Jun; Htoon, Hla M; Aung, Tin; Vithana, Eranga N

2013-01-01

To characterize the relative expression levels of all the solute carrier 4 (Slc4) transporter family members (Slc4a1-Slc4a11) in murine corneal endothelium using real-time quantitative (qPCR), to identify further important members besides Slc4a11 and Slc4a4, and to explore how close to the baseline levels the gene expressions remain after cells have been subjected to expansion and culture. Descemet's membrane-endothelial layers of 8-10-week-old C57BL6 mice were stripped from corneas and used for both primary cell culture and direct RNA extraction. Total RNA (from uncultured cells as well as cultured cells at passages 2 and 7) was reverse transcribed, and the cDNA was used for real time qPCR using specific primers for all the Slc4 family members. The geNorm method was applied to determine the most stable housekeeping genes and normalization factor, which was calculated from multiple housekeeping genes for more accurate and robust quantification. qPCR analyses revealed that all Slc4 bicarbonate transporter family members were expressed in mouse corneal endothelium. Slc4a11 showed the highest expression, which was approximately three times higher than that of Slc4a4 (3.4±0.3; p=0.004). All Slc4 genes were also expressed in cultured cells, and interestingly, the expression of Slc4a11 in cultured cells was significantly reduced by approximately 20-fold (0.05±0.001; p=0.000001) in early passage and by approximately sevenfold (0.14±0.002; p=0.000002) in late passage cells. Given the known involvement of SLC4A4 and SLC4A11 in corneal dystrophies, we speculate that the other two highly expressed genes in the uncultured corneal endothelium, SLC4A2 and SLC4A7, are worthy of being considered as potential candidate genes for corneal endothelial diseases. Moreover, as cell culture can affect expression levels of Slc4 genes, caution and careful design of experiments are necessary when undertaking studies of Slc4-mediated ion transport in cultured cells.

Evaluation of corneal higher order aberrations in normal topographic patterns

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Ali Mirzajani

2016-06-01

Conclusions: Based on results in this study, there were a good correlation between corneal topographic pattern and corneal HOAs in normal eyes. These results indicate that the corneal HOAs values are largely determined by the topographic patterns. A larger sample size would perhaps have been beneficial to yield in more accurate outcomes.

Ultraviolet induced lysosome activity in corneal epithelium

International Nuclear Information System (INIS)

Cullen, A.P.

1980-01-01

A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm -2 to 10.000 Jm -2 and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm -2 and lens threshold (Hsub(L)) was 7.500 Jm -2 . The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared. (orig.) [de

Alteraciones corneales en pacientes diabéticos

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Iraisi Hormigó Puertas

Full Text Available La diabetes mellitus, afección frecuente a nivel mundial, tiene gran impacto en la sociedad no solo por su alta prevalencia, sino por sus complicaciones crónicas y su alta mortalidad. Afecta a unos 180 millones de personas en el mundo. La prevalencia de la diabetes (tipos I y II se estima en el 13 % en pacientes mayores de 60 años. La estructura corneal sufre modificaciones en los pacientes diabéticos; la hiperglucemia afecta la hidratación de la córnea, y con esto varía el espesor corneal y aparecen cambios queratométricos visibles mediante topografía corneal. Las córneas de los pacientes con diabetes presentan alteraciones epiteliales, estromales y endoteliales. Además, existe una disminución de la permeabilidad endotelial durante la fase de hipoxia, que relacionan estos efectos de la diabetes en las células endoteliales. El objetivo de nuestro estudio es abordar las diferentes alteraciones corneales en los pacientes diabéticos.

Humanized mouse models: Application to human diseases.

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Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Effect of Viscous Agents on Corneal Density in Dry Eye Disease.

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Wegener, Alfred R; Meyer, Linda M; Schönfeld, Carl-Ludwig

2015-10-01

To investigate the effect of the viscous agents, hydroxypropyl methylcellulose (HPMC), carbomer, povidone, and a combination of HPMC and povidone on corneal density in patients with dry eye disease. In total, 98 eyes of 49 patients suffering from dry eye and 65 eyes of 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and corneal density was analyzed in 5 anatomical layers (epithelium, bowman membrane, stroma, descemet's membrane, and endothelium). Corneal density was evaluated for the active ingredients HPMC, carbomer, povidone, and a combination of HPMC and povidone as the viscous agents contained in the artificial tear formulations used by the dry eye patients. Data were compared to the age-matched healthy control group without medication. Corneal density in dry eye patients was reduced in all 5 anatomical layers compared to controls. Corneal density was highest and very close to control in patients treated with HPMC containing ocular lubricants. Patients treated with lubricants, including carbomer as the viscous agent displayed a significant reduction of corneal density in layers 1 and 2 compared to control. HPMC containing ocular lubricants can help to maintain physiological corneal density and may be beneficial in the treatment of dry eye disease.

Healed corneal ulcer with keloid formation

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Alkatan, Hind M.; Al-Arfaj, Khalid M.; Hantera, Mohammed; Al-Kharashi, Soliman

2012-01-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman’s layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a co...

Mouse models of estrogen receptor-positive breast cancer

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Shakur Mohibi

2011-01-01

Full Text Available Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

Corneal thickness changes during corneal collagen cross-linking with UV-A irradiation and hypo-osmolar riboflavin in thin corneas

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Belquiz Amaral Nassaralla

2013-06-01

Full Text Available PURPOSE: To evaluate the thinnest corneal thickness changes during and after corneal collagen cross-linking treatment with ultraviolet-A irradiation, using hypo-osmolar riboflavin solution in thin corneas. METHODS: Eighteen eyes of 18 patients were included in this study. After epithelium removal, iso-osmolar 0.1% riboflavin solution was instilled to the cornea every 3 minutes for 30 minutes. Hypo-osmolar 0.1% riboflavin solution was then applied every 20 seconds for 5 minutes or until the thinnest corneal thickness reached 400 µm. Ultraviolet-A irradiation was performed for 30 minutes. During irradiation, iso-osmolar 0.1% riboflavin drops were applied every 5 minutes. Ultrasound pachymetry was performed at approximately the thinnest point of the cornea preoperatively, after epithelial removal, after iso-osmolar riboflavin instillation, after hypo-osmolar riboflavin instillation, after ultraviolet-A irradiation, and at 1, 6 and 12 months after treatment. RESULTS: Mean preoperative thinnest corneal thickness was 380 ± 11 µm. After epithelial removal it decreased to 341 ± 11 µm, and after 30 minutes of iso-osmolar 0.1% riboflavin drops, to 330 ± 7.6 µm. After hypo-osmolar 0.1% riboflavin drops, mean thinnest corneal thickness increased to 418 ± 11 µm. After UVA irradiation, it was 384 ± 10 µm. At 1, 6 and 12 months after treatment, it was 372 ± 10 µm, 381 ± 12.7, and 379 ± 15 µm, respectively. No intraoperative, early postoperative, or late postoperative complications were noted. CONCLUSIONS: Hypo-osmolar 0.1% riboflavin solution seems to be effective for swelling thin corneas. The swelling effect is transient and short acting. Corneal thickness should be monitored throughout the procedure. Larger sample sizes and longer follow-up are required in order to make meaningful conclusions regarding safety.

CD147 required for corneal endothelial lactate transport.

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Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

2014-06-26

CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Eye abnormalities in the mouse fetus and postnatal mice caused by x-radiation of 150 R on the 7th day of gestation

International Nuclear Information System (INIS)

Hashimoto, Masaru

1976-01-01

X-ray of 150 R was irradiated once to the whole body of ddN mouse on the 7th day of gestation, and eye abnormalities in the mouse embryos of 18 days and in mouse youngs of 4 weeks after birth were observed externally and histologically. In the observation of the mouse embryos of 18 days, microphthalmus, anophthalmia, retinal reversion and distorsion due to eyecup insufficiency, and cornea abnormalities were recognized, and these eye abnormalities were also recognized in the mouse youngs of 4 weeks. Histological findings of congenital corneal opacity and accretion of the cornea and the crystalline lens in the mouse youngs and the mouse embryos of 18 days were the same kinds, and a common feature was the defect of the corneal parenchyma. These were caused by disorder of segregation from ectoblast of epidermis cuticle of crystalline lens. Histological findings equal to that of hereditary defect of the uvea were recognized after birth, and histological findings which seemed to be changes during the embryonal period were obtained. This was thought to be caused by eyecup insufficiency. Histological findings as same as those of clinical ''Retinal Dysplasia'' were obtained in mice after birth, and embryos with retinal distorsion, strong primary residue of the vitreous body, and defect of the choriod, which seemed to be changes of retinal dysplasia during the embryonal period, were recognized. This was thought to be caused by eyecup insufficiency. Anophthalmia was observed in the embryos and the youngs, there were some traces of eye tissues, and all cases were secondary anophthalmus. Aphacia which was found in the embryos was not recognized in any case of the young after birth. (tsunoda, M.)

Case Report: Corneal Pyogenic Granuloma: Rare Complication of ...

African Journals Online (AJOL)

Slit lamp examination showed vascularized central corneal mass with surrounding stromal infiltrates. The mass was excised, and histopathological examination confirmed pyogenic granuloma of the cornea. Conclusion: Corneal pyogenic granuloma could be a rare complication of infectious keratitis. Therefore, it should be ...

Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

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Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

2014-07-01

International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment. © 2014 by The Author(s).

Mouse models of long QT syndrome

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Salama, Guy; London, Barry

2007-01-01

Congenital long QT syndrome is a rare inherited condition characterized by prolongation of action potential duration (APD) in cardiac myocytes, prolongation of the QT interval on the surface electrocardiogram (ECG), and an increased risk of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of cardiac ion channel genes that affect repolarization cause the majority of the congenital cases. Despite detailed characterizations of the mutated ion channels at the molecular level, a complete understanding of the mechanisms by which individual mutations may lead to arrhythmias and sudden death requires study of the intact heart and its modulation by the autonomic nervous system. Here, we will review studies of molecularly engineered mice with mutations in the genes (a) known to cause long QT syndrome in humans and (b) specific to cardiac repolarization in the mouse. Our goal is to provide the reader with a comprehensive overview of mouse models with long QT syndrome and to emphasize the advantages and limitations of these models. PMID:17038432

A STUDY ON PREVALENCE AND CAUSES OF CORNEAL BLINDNESS IN PAEDIATRIC AGE GROUP

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E. Ramadevi

2017-12-01

Full Text Available BACKGROUND Corneal disease is responsible for less than 2% of blindness in children in industrialised countries. In poor countries of the world, corneal scarring occurs due to vitamin A deficiency, measles and ophthalmia neonatorum. Thus, corneal disease is an important cause of blindness among children living in developing nations, which already carry a major burden of blindness. The aim of the study is to study the1. Prevalence of corneal blindness in the paediatric age group. 2. Causes of corneal blindness in the paediatric age group. 3. Morbidity of corneal blindness in the paediatric age group. MATERIALS AND METHODS It was cross-sectional observational study. Study Period- December 2014 to August 2016. Study Done- Government General Hospital, Kakinada. Sample Size- 50 patients. Inclusion Criteria- Children of age group 6 to 12 years with corneal blindness who have attended the outpatient department during the study period. Exclusion Criteria- Children with childhood blindness other than corneal pathology. Study Tools- Predesigned, semi-structured questionnaire regarding age, sex and age of onset of visual loss, laterality, history of ocular injury, vitamin A immunisation, family history of consanguinity and place of residence and socioeconomic status was taken. Visual acuity was measured using an E optotype and Landolt broken C chart with best corrected vision. Visual loss was classified according to the WHO categories of visual impairment. Ophthalmic examination was done by slit lamp and B scan. RESULTS Ocular trauma and corneal ulcers are most common cause of corneal blindness. 84% of corneal blindness cases were preventable and curable. CONCLUSION Trauma was the commonest cause of corneal blindness followed by infectious keratitis. 84% of corneal blindness was preventable and curable. Most causes of corneal blindness were avoidable.

Alternatives to eye bank native tissue for corneal stromal replacement.

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Brunette, Isabelle; Roberts, Cynthia J; Vidal, François; Harissi-Dagher, Mona; Lachaine, Jean; Sheardown, Heather; Durr, Georges M; Proulx, Stéphanie; Griffith, May

2017-07-01

Corneal blindness is a major cause of blindness in the world and corneal transplantation is the only widely accepted treatment to restore sight in these eyes. However, it is becoming increasingly difficult for eye banks to meet the increasing demand for transplantable tissue, which is in part due to population aging. Donor tissue shortage is therefore a growing concern globally and there is a need for alternatives to human donor corneas. Biosynthetic corneal substitutes offer several significant advantages over native corneas: Large-scale production offers a powerful potential solution to the severe shortage of human donor corneas worldwide; Good manufacturing practices ensure sterility and quality control; Acellular corneal substitutes circumvent immune rejection induced by allogeneic cells; Optical and biomechanical properties of the implants can be adapted to the clinical need; and finally these corneal substitutes could benefit from new advances in biomaterials science, such as surface coating, functionalization and nanoparticles. This review highlights critical contributions from laboratories working on corneal stromal substitutes. It focuses on synthetic inert prostheses (keratoprostheses), acellular scaffolds with and without enhancement of endogenous regeneration, and cell-based replacements. Accent is put on the physical properties and biocompatibility of these biomaterials, on the functional and clinical outcome once transplanted in vivo in animal or human eyes, as well as on the main challenges of corneal stromal replacement. Regulatory and economic aspects are also discussed. All of these perspectives combined highlight the founding principles of the clinical application of corneal stromal replacement, a concept that has now become reality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defining the role of polyamines in colon carcinogenesis using mouse models

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Natalia A Ignatenko

2011-01-01

Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

Excimer laser corneal surgery and free oxygen radicals.

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Bilgihan, K; Bilgihan, A; Akata, F; Hasanreisoğlu, B; Türközkan, N

1996-01-01

Corneal photoablation with 193 nm argon fluoride excimer laser is a new technique for the treatment of refractive errors and for removing corneal opacities and irregularities. Ultraviolet radiation and thermal injury induce free radical formation in the tissues. The aim of this study was to confirm the production of free radicals by excimer laser photoablation in rabbits. The thermal changes of the posterior corneal surface were recorded during excimer laser photoablation. The lipid peroxide (LPO) levels and superoxide dismutase (SOD) activities of aqueous humour were measured after excimer laser keratectomy. The aqueous LPO levels were not changed after excimer laser ablation, but both the thermal increase in the cornea during the photoablation and the decreased aqueous SOD activities suggest that free radicals are formed in the cornea during excimer laser keratectomy, and that they may be responsible for some of the complications of excimer laser corneal surgery.

Distrofia corneal granular

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Alexeide de la C Castillo Pérez

Full Text Available Las distrofias corneales constituyen un conjunto de enfermedades que presentan, en su mayoría, una baja incidencia y se caracterizan por acúmulo de material hialino o amiloide que disminuyen la transparencia corneal. La distrofia granular es una enfermedad autosómica dominante que presenta opacidades grises en el estroma superficial central de la córnea y se hacen visibles en la primera y segunda décadas de la vida, lo que provoca disminución de la visión más significativa cerca de los 40 años de edad. Presentamos dos casos clínicos de distrofia granular en pacientes hermanos de diferentes sexos, quienes acudieron a la consulta y refirieron visión nublada. El estudio de la historia familiar nos ayuda en el correcto diagnóstico y la biomicroscopia constituye el elemento más importante.

The theory and art of corneal cross-linking.

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McQuaid, Rebecca; Cummings, Arthur B; Mrochen, Michael

2013-08-01

Before the discovery of corneal cross-linking (CXL), patients with keratoconus would have had to undergo corneal transplantation, or wear rigid gas permeable lenses (RGPs) that would temporarily flatten the cone, thereby improving the vision. The RGP contact lens (CL) would not however alter the corneal stability and if the keratoconus was progressive, the continued steepening of the cone would occur under the RGP CL. To date, the Siena Eye has been the largest study to investigate long term effects of standard CXL. Three hundred and sixty-three eyes were treated and monitored over 4 years, producing reliable long-term results proving long-term stability of the cornea by halting the progression of keratoconus, and proving the safety of the procedure. Traditionally, CXL requires epithelial removal prior to corneal soakage of a dextran-based 0.1% riboflavin solution, followed by exposure of ultraviolet-A (UV-A) light for 30 min with an intensity of 3 mW/cm2. A series of in vitro investigations on human and porcine corneas examined the best treatment parameters for standard CXL, such as riboflavin concentration, intensity, wavelength of UV-A light, and duration of treatment. Photochemically, CXL is achieved by the generation of chemical bonds within the corneal stroma through localized photopolymerization, strengthening the cornea whilst minimizing exposure to the surrounding structures of the eye. In vitro studies have shown that CXL has an effect on the biomechanical properties of the cornea, with an increased corneal rigidity of approximately 70%. This is a result of the creation of new chemical bonds within the stroma.

Unilateral corneal leukoplakia without limbal involvement

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Hirano K

2015-05-01

Full Text Available Koji Hirano,1 Mihoko Koide,2 Yoshikazu Mizoguchi,3 Yasuhiro Osakabe,4 Kaoru-Araki Sasaki5 1Department of Ophthalmology, Ban Buntane Hotokukai Hospital, School of Medicine, Fujita Health University, Nagoya, Japan; 2Koide Internal Medicine and Eye Clinic, Nagoya, Japan; 3Department of Pathology, Ban Buntane Hotokukai Hospital, School of Medicine, Fujita Health University, Nagoya, Japan; 4Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan; 5Department of Ophthalmology, Japan Health Care Organization, Hoshigaoka Medical Center, Hirakata, Japan Purpose: Leukoplakia is the term given to a white patch or plaque that is found mainly on the oral mucus membrane. It can occasionally be seen on the corneal surface. We report our clinical and histopathological findings in a case of unilateral corneal leukoplakia. Methods: A 26-year-old woman was referred to our hospital because of a white patch on her right cornea that continued to expand. She first noticed the white patch when she was 20 years old, and the white patch had expanded to cover the pupillary area affecting her vision. After plastic surgery on both eyelids for bilateral entropion to alleviate the pain caused by the eyelashes rubbing the cornea, the white corneal patch decreased in size. Because of this reduction, we performed surgery to remove the patch with microforceps under topical anesthesia. The plaque was removed easily and completely, and submitted for histopathological examination. Results: Histopathological examination showed that the specimen had characteristics of epidermis with a basal cell layer, spinous cell layer, granular cell layer, and horny layer with hyperkeratosis. She was diagnosed with leukoplakia of the corneal surface. The basic structure of the squamous cell layer was preserved, and there were no signs of metaplasia. Six months after the removal of the leukoplakia, no recurrence was seen and her corrected decimal visual acuity recovered to 1

Corneal elastosis within lattice dystrophy lesions.

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Pe'er, J; Fine, B S; Dixon, A; Rothberg, D S

1988-01-01

Corneal buttons of two patients with lattice corneal dystrophy were studied by light and electron microscopy. They showed elastotic degeneration within the amyloid deposits. The amyloid deposits displayed characteristic staining; the elastotic material (elastin) within the deposits stained positive with Verhoeff-van Gieson and Movat pentachrome stains and showed autofluorescence. The characteristic ultrastructural findings of amyloid and elastotic material were also demonstrated. The possibility of the associations of these two materials in the cornea is discussed. Images PMID:3258531

Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

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Harold Tjalsma

Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

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Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Image quality of grating target in model eye when viewed through a small-aperture corneal inlay.

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Inoue, Makoto; Bissen-Miyajima, Hiroko; Arai, Hiroyuki; Noda, Toru; Ohnuma, Kazuhiko; Hirakata, Akito

2014-07-01

To evaluate the quality of the image of a grating target placed in a model eye and viewed through a small-aperture corneal inlay. Kyorin Eye Center, Tokyo, Japan. Experimental study. A Kamra corneal inlay was placed on the anterior surface of a fluid-filled model eye, and a United States Air Force target and a calibrated scale were placed on the inner surface of the model eye. With a flat contact lens or a contact or noncontact wide-angle viewing system, the contrast of the grating images and the field of view through the inlay were compared with those without the inlay. A blurred dark ring was observed with the flat contact lens and MiniQuad wide-viewing contact lens in the model eye with the inlay. The contrast of the gratings was significantly decreased at 16 cycles/mm (P=.028), 32 cycles/mm (P=.046), and 64 cycles/mm (P=.015). With the Resight noncontact wide-angle viewing system, the field of view was reduced from 62 degrees to 32 degrees when the front lens was at 7.0 mm and slightly reduced from 75 degrees to 62 degrees at 5.0 mm with the inlay. The contrast of grating images observed through the inlay was significantly reduced when viewed with the flat contact lens. The field of view through the wide-angle viewing system was also altered. However, the noncontact wide-angle viewing system may be recommended for vitreous surgeries in eyes with the inlay by adjusting the distance of the front lens from the cornea. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Do topical antibiotics help corneal epithelial trauma?

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King, J. W.; Brison, R. J.

1993-01-01

Topical antibiotics are routinely used in emergency rooms to treat corneal trauma, although no published evidence supports this treatment. In a noncomparative clinical trial, 351 patients with corneal epithelial injuries were treated without antibiotics. The infection rate was 0.7%, suggesting that such injuries can be safely and effectively managed without antibiotics. A comparative clinical trial is neither warranted nor feasible.

Applications of biomaterials in corneal wound healing

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I-Lun Tsai

2015-04-01

Full Text Available Disease affecting the cornea is a common cause of blindness worldwide. To date, the amniotic membrane (AM is the most widely used clinical method for cornea regeneration. However, donor-dependent differences in the AM may result in variable clinical outcomes. To overcome this issue, biomaterials are currently under investigation for corneal regeneration in vitro and in vivo. In this article, we highlight the recent advances in hydrogels, bioengineered prosthetic devices, contact lenses, and drug delivery systems for corneal regeneration. In clinical studies, the therapeutic effects of biomaterials, including fibrin and collagen-based hydrogels and silicone contact lenses, have been demonstrated in damaged cornea. The combination of cells and biomaterials may provide potential treatment in corneal wound healing in the future.

Comparative analysis of corneal morphological changes after transversal and torsional phacoemulsification through 2.2 mm corneal incision

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Assaf A

2013-01-01

Full Text Available Ahmed Assaf, Maged Maher RoshdyOphthalmology Department, Ain Shams University, Cairo, EgyptPurpose: This paper compares and evaluates the corneal morphological changes occurring after cataract surgery through a 2.2 mm corneal incision. We use two platforms for comparison and evaluation, transversal and torsional phacoemulsification.Patients and methods: This study includes 139 consecutive cataractous eyes (nuclear color 2–4, according to the Lens Opacities Classification System III [LOCSIII] of 82 patients undergoing cataract surgery through a 2.2 mm corneal incision. Two different phacoemulsification platforms were used and assigned randomly: we used the WhiteStar Signature® system with the Ellips™ FX transversal continuous ultrasound (US mode for group I (mean age: 65.33 ± 6.97 years, and we used the Infiniti® system with the OZil® Intelligent Phaco (IP torsional US mode for group II (mean age: 64.02 ± 7.55 years. The corneal endothelium and pachymetry were evaluated preoperatively and at 1 month postoperatively. Incision size changes were also evaluated.Results: All surgeries were uneventful. Before intraocular lens implantation, the mean incision size was 2.24 ± 0.06 mm in both groups (P = 0.75. In terms of corneal endothelial cell density, neither preoperative (I vs II: 2304.1 ± 122.5 cell/mm2 vs 2315.6 ± 83.1 cell/mm2, P = 0.80 nor postoperative (I vs II: 2264.1 ± 124.3 cell/mm2 vs 2270.3 ± 89.9 cell/mm2, P = 0.98 differences between the groups were statistically significant. The mean endothelial cell density loss was 1.7% ± 1.6% and 2.0% ± 1.4% in groups I and II, respectively. Furthermore, no significant differences between groups I and II were found preoperatively (P = 0.40 and postoperatively (P = 0.68 in central pachymetry. With surgery, the mean increase in central pachymetry was 28.1 ± 23.6 µm and 24.0 ± 24.0 µm in groups I and II, respectively (P = 0.1.Conclusion: Ellips™ FX transversal and OZil® IP torsional

Inhibition of Corneal Neovascularization by Topical and Subconjunctival Tigecycline

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Sertan Goktas

2014-01-01

Full Text Available Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1 or subconjunctival instillation of 1 mg/mL tigecycline (group 3 for 7 days. Control rats received topical (group 2 or subconjunctival (group 4 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI, 44.2–55.8% and 33.5% (95% CI, 26.6–39.2%, respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P=0.03 and P<0.001, resp.. Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.

Thick keratoconic cornea associated with posterior polymorphous corneal dystrophy.

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Zaarour, K; Slim, E; Antoun, J; Waked, N

2017-03-01

We herein report a case of bilateral unusually thick non-edematous keratoconic corneas with associated endothelial features of posterior polymorphous corneal dystrophy (PPCD). We report the case of a 27-year-old myopic woman who presented for refractive surgery. Slit lamp exam showed bilateral corneal protrusion with diffuse deep stromal and endothelial vesicular opacities and small paracentral bands. Topography showed generalized advanced corneal steepening in both eyes with increased anterior and posterior central corneal elevations in comparison to the best fit sphere. Ultrasound pachymetry showed central corneal thickness of 605μm (RE) and 612μm (LE). On specular biomicroscopy, cell density of 2503 cells/mm 2 RE and 1526 cells/mm 2 LE with significant cellular pleomorphism and polymegathism were noted. Clinical and paraclinical findings together suggest the presence of simultaneous keratoconus and PPCD. The literature has suggested an association between PPCD and steep cornea. Moreover, many reports have also described cases of associated PPCD and keratoconus with characteristic thinning and ectasia, in comparison to the unusual thick corneas noted in our patient, despite the absence of edema. Identification of genetics factors is further needed to clarify this association. This case describes a patient whose corneas present features of both keratoconus and PPCD and is unique due to the presence of increased corneal thickness despite the absence of edema. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Biomechanical corneal changes induced by different flap thickness created by femtosecond laser

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Fabricio W. Medeiros

2011-01-01

Full Text Available OBJECTIVE: To evaluate the impact of the creation of corneal flaps at different thicknesses on the biomechanical properties of swine corneas. METHOD: Twelve swine eyes were obtained to form two groups: 100 μm flap thickness and 300 μm flap thickness. Each eye was submitted to the following examinations: raster topography to investigate corneal curvature alterations, ocular response analyzer to investigate corneal hysteresis change, optical coherence tomography to measure central corneal and flap thickness and sonic wave propagation velocity as a measure of stiffness, before and immediately after flap creation. After flap amputation, surface wave velocity measurements were repeated. RESULTS: Measured flap thicknesses were statistically different for thin and thick flap groups, with an average of 108.5 + 6.9 and 307.8 + 11.5 μm respectively. Hysteresis and corneal resistance factor did not change significantly after flap creation in the thin flap group. With thicker flaps, both parameters decreased significantly from 8.0 +1.0 to 5.1 +1.5 mmHg and from 8.2 + 1.6 to 4.1 +2.5 mmHg respectively. Simulated keratometry values increased in the thick flap group (from 39.5 + 1 D to 45.9+1.2 D after flap creation but not in the thin flap group (from 40.6 + 0.6 D to 41.4+ 1.0 D. Regarding surface wave velocity analysis, the surgical procedures induced statistically lower results in some positions. CONCLUSION: In the experimental conditions established by this model, thicker flaps presented a greater biomechanical impact on the cornea.

Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

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Uhl, Elizabeth W; Warner, Natalie J

Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

Influence of different phacoemulsification incision on postoperative corneal astigmatism for cataract patients

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Zhao-Rong Zeng

2014-05-01

Full Text Available AIM: To compare the effect of different phacoemulsification incision on postoperative corneal astigmatism for cataract patients. METHODS: The cataract patients were selected in our hospital. The patients were divided into control group(corneal limbus opposite curved scleral tunnel incision groupand observation group(above the top of cornea or temporal transparent corneal incision grouprandomly. At 1wk; 1 and 3mo after surgery, the change of corneal astigmatism and vision of the patients in two groups were compared and analyzed. RESULTS:Compared with control group, 1wk; 1 and 3mo after surgery, the average corneal astigmatism and surgically induced corneal astigmatism of the patients in observation group were decreased significantly. The visual acuity and corrected visual acuity were increased significantly. There was statistically significant(PPCONCLUSION: Center distance and small incision corneal phacoemulsification can reduce postoperative astigmatism and improve postoperative visual acuity for cataract patients. It provides guarantee for further strengthen the clinical treated effect for cataract patients.

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns

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Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

2016-01-01

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties. PMID:27057279

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

Science.gov (United States)

Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

2016-01-01

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns

Directory of Open Access Journals (Sweden)

Cestmir Cejka

2016-01-01

Full Text Available The aim of this study was to examine whether mesenchymal stem cells (MSCs and/or corneal limbal epithelial stem cells (LSCs influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs, with adipose tissue MSCs (Ad-MSCs, or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9, inducible nitric oxide synthase (iNOS, α-smooth muscle actin (α-SMA, transforming growth factor-β1 (TGF-β1, and vascular endothelial factor (VEGF were low. The central corneal thickness (taken as an index of corneal hydration increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

Ultraviolet induced lysosome activity in corneal epithelium

Energy Technology Data Exchange (ETDEWEB)

Cullen, A.P.

1980-01-01

A 5.000 W Xe-Hg high pressure lamp and a double monochromator were used to produce a 3.3 nm half-bandpass ultraviolet radiation at 295 nm. Pigmented rabbit eyes were irradiated with radiant exposures from 140 Jm/sup -2/ to 10.000 Jm/sup -2/ and evaluated by slit-lamp biomicroscopy, light and electron microscopy. Corneal threshold (Hsub(c) was 200 Jm/sup -2/ and lens threshold (Hsub(L)) was 7.500 Jm/sup -2/. The most repeatable and reliable corneal response to these levels of UV was the development of corneal epithelial granules. Histological changes included a loss of superficial epithelial cells and selective UV induced autolysis of the wing cells. It is suggested that the biomicroscopically observed granules are the clinical manifestation of the secondary lysosomes revealed by light and electron microscopy. It is proposed that UV breaks down the primary lysosome membranes to release hydrolytic enzymes which in turn form the secondary lysosomes during autolysis. Extreme levels of radiant exposure at 295 nm result in indiscriminate destruction of all layers of the corneal epithelium, but the posterior cornea was spared.

Integrin α5β1 Inhibition by CLT-28643 Reduces Postoperative Wound Healing in a Mouse Model of Glaucoma Filtration Surgery.

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Van Bergen, Tine; Zahn, Grit; Caldirola, Patrizia; Fsadni, Mario; Caram-Lelham, Ninus; Vandewalle, Evelien; Moons, Lieve; Stalmans, Ingeborg

2016-11-01

To evaluate the therapeutic potential of the small molecule integrin α5β1 inhibitor, CLT-28643, to improve the filtering surgery outcome in a mouse model. Different dose regimens and administration routes of the inhibitor were compared with mitomycin C (MMC), the gold standard in clin ical practice. The efficacy of CLT-28643 on surgical outcome was studied in a mouse model for filtering surgery (n = 40 eyes from 20 mice per group). Single and repeated subconjunctival (SCJ) injections (1 or 2 μg) and topical eye drops (10 μg) of the integrin inhibitor were compared with 2-minute administration of MMC 0.02%. Bleb size, survival, and signs of toxicity were examined until 28 days after surgery. Immunohistochemical analysis of angiogenesis, inflammation, collagen deposition, and integrin α5β1 expression were performed on postoperative days 3, 8, 14, and 28. A masked observer performed all the assessments. Immunostaining showed that integrin α5β1 was highly expressed in the bleb at early time-points after surgery and that CLT-28643 inhibited this upregulation. Efficacy was shown to be dose-dependent for the integrin inhibitor CLT-28643 for bleb area and survival, and the wound healing process. While 2-μg single injection of CLT-28643 improved bleb characteristics in a similar way as 10-μg administered by eye drops and MMC, repeated injections of 2 μg showed superior efficacy compared to MMC, with no corneal toxicity. Administration of the integrin α5β1 inhibitor CLT-28643 has therapeutic potential as an adjunct to glaucoma surgery, possibly with a superior efficacy and tolerability compared with MMC when used at the optimal dose.

Aloe vera: an in vitro study of effects on corneal wound closure and collagenase activity.

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Curto, Elizabeth M; Labelle, Amber; Chandler, Heather L

2014-11-01

To evaluate the in vitro effects of an aloe vera solution on (i) the viability and wound healing response of corneal cells and (ii) the ability to alter collagenase and gelatinase activities. Primary cultures of corneal epithelial cells and fibroblasts were prepared from grossly normal enucleated canine globes and treated with an aloe solution (doses ranging from 0.0-2 mg/mL). Cellular viability was evaluated using a colorimetric assay. A corneal wound healing model was used to quantify cellular ingrowth across a defect made on the confluent surface. Anticollagenase and antigelatinase activities were evaluated by incubating a bacterial collagenase/gelatinase with aloe solution (doses ranging from 0.0-500 μg/mL) and comparing outcome measures to a general metalloproteinase inhibitor, 1, 10-phenanthroline, and canine serum (doses ranging from 0.0-100%). None of the concentrations of aloe solution tested significantly affected the viability of corneal epithelial cells or fibroblasts. Concentrations ≤175 μg/mL slightly accelerated corneal epithelial cell wound closure; this change was not significant. Concentrations ≥175 μg/mL significantly (P ≤ 0.001) slowed the rate of corneal fibroblast wound closure, while aloe concentrations Aloe solution did not alter the ability for collagenase to degrade gelatin or collagen Type I but increased the ability for collagenase to degrade Type IV collagen. Although additional experiments are required, lower concentrations of aloe solution may be beneficial in healing of superficial corneal wounds to help decrease fibrosis and speed epithelialization. An increase in collagenase activity with aloe vera warrants further testing before considering in vivo studies. © 2014 American College of Veterinary Ophthalmologists.

Mouse models for gastric cancer: Matching models to biological questions

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Poh, Ashleigh R; O'Donoghue, Robert J J

2016-01-01

Abstract Gastric cancer is the third leading cause of cancer‐related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late‐stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new‐targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre‐clinical development of new therapeutics. PMID:26809278

The theory and art of corneal cross-linking

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Rebecca McQuaid

2013-01-01

Full Text Available Before the discovery of corneal cross-linking (CXL, patients with keratoconus would have had to undergo corneal transplantation, or wear rigid gas permeable lenses (RGPs that would temporarily flatten the cone, thereby improving the vision. The RGP contact lens (CL would not however alter the corneal stability and if the keratoconus was progressive, the continued steepening of the cone would occur under the RGP CL. To date, the Siena Eye has been the largest study to investigate long term effects of standard CXL. Three hundred and sixty-three eyes were treated and monitored over 4 years, producing reliable long-term results proving long-term stability of the cornea by halting the progression of keratoconus, and proving the safety of the procedure. Traditionally, CXL requires epithelial removal prior to corneal soakage of a dextran-based 0.1% riboflavin solution, followed by exposure of ultraviolet-A (UV-A light for 30 min with an intensity of 3 mW/cm2. A series of in vitro investigations on human and porcine corneas examined the best treatment parameters for standard CXL, such as riboflavin concentration, intensity, wavelength of UV-A light, and duration of treatment. Photochemically, CXL is achieved by the generation of chemical bonds within the corneal stroma through localized photopolymerization, strengthening the cornea whilst minimizing exposure to the surrounding structures of the eye. In vitro studies have shown that CXL has an effect on the biomechanical properties of the cornea, with an increased corneal rigidity of approximately 70%. This is a result of the creation of new chemical bonds within the stroma.

Effect of corneal cross-linking on contact lens tolerance in keratoconus.

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Ünlü, Metin; Yüksel, Erdem; Bilgihan, Kamil

2017-07-01

The aim was to investigate changes in corneal sensation and rigid gas-permeable (RGP) contact lens tolerance after corneal cross-linking (CXL) on patients with keratoconus. Thirty eyes of 30 patients, who were RGP lens intolerant, were treated with CXL. The main outcome measures were corneal sensation evaluation by Cochet-Bonnet esthesiometry, sub-basal nerve fibre assessment by corneal in vivo confocal microscopy and RGP contact lens tolerance evaluation with the Likert scale and wearing time. All eyes were evaluated preoperatively and post-operatively at one, three and six months after CXL procedure. The mean age was 25.3 ± 6.2 years. Preoperatively, the maximum keratometry (Kmax) in study eyes was 56.89 ± 4.60 D. Six months after CXL, it reduced to 56.03 ± 4.85 D (p = 0.01). Preoperative mean corneal sensation was 0.44 ± 0.05 g/mm 2 , (range: 0.40 to 0.55); it was significantly decreased at the first month and increased to preoperative values after six months. The sub-basal nerve plexus could not be visualised in 90 per cent of the patients by confocal microscopy at one month post-operatively. Gradual restoration of corneal innervation with almost similar preoperative levels at post-operative month six was noted. There were significant differences in Likert scores between preoperative and third and sixth months after CXL. Likert scale scores correlated significantly with corneal sensitivity. It can be concluded that increased RGP contact lens tolerance after CXL may be associated with the potential role of decreased corneal sensitivity and corneal flattening after CXL. © 2016 Optometry Australia.

Histologic scoring of gastritis and gastric cancer in mouse models.

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Rogers, Arlin B

2012-01-01

Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.

Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

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Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David

2016-06-01

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Selective corneal optical aberration (SCOA) for customized ablation

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Jean, Benedikt J.; Bende, Thomas

2001-06-01

Wavefront analysis still have some technical problems which may be solved within the next years. There are some limitations to use wavefront as a diagnostic tool for customized ablation alone. An ideal combination would be wavefront and topography. Meanwhile Selective Corneal Aberration is a method to visualize the optical quality of a measured corneal surface. It is based on a true measured 3D elevation information of a video topometer. Thus values can be interpreted either using Zernike polynomials or visualized as a so called color coded surface quality map. This map gives a quality factor (corneal aberration) for each measured point of the cornea.

TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

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Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

2017-07-01

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

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Samala, Ramakrishna; Willis, Sarah; Borges, Karin

2008-10-01

Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

[Corneal manifestations in systemic diseases].

Science.gov (United States)

Zarranz Ventura, J; De Nova, E; Moreno-Montañés, J

2008-01-01

Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

Excimer laser-assisted anterior lamellar keratoplasty for keratoconus, corneal problems after laser in situ keratomileusis, and corneal stromal opacities.

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Bilgihan, Kamil; Ozdek, Sengül C; Sari, Ayça; Hasanreisoğlu, Berati

2006-08-01

To evaluate excimer laser-assisted anterior lamellar keratoplasty to augment thin corneas as in keratoconus ( .05). This technique presents a different modality for the treatment of keratoconus, post-LASIK corneal problems, and other corneal stromal opacities with anterior lamellar keratoplasty. Additional studies with more patients and longer follow-up will help determine the role of this technique as a substitute for penetrating keratoplasty in these patients.

The STR/ort mouse model of spontaneous osteoarthritis - an update.

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Staines, K A; Poulet, B; Wentworth, D N; Pitsillides, A A

2017-06-01

Osteoarthritis is a degenerative joint disease and a world-wide healthcare burden. Characterized by cartilage degradation, subchondral bone thickening and osteophyte formation, osteoarthritis inflicts much pain and suffering, for which there are currently no disease-modifying treatments available. Mouse models of osteoarthritis are proving critical in advancing our understanding of the underpinning molecular mechanisms. The STR/ort mouse is a well-recognized model which develops a natural form of osteoarthritis very similar to the human disease. In this Review we discuss the use of the STR/ort mouse in understanding this multifactorial disease with an emphasis on recent advances in its genetics and its bone, endochondral and immune phenotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Research on inhibition of corneal neovascularization

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Zhang-Hui Yang

2015-12-01

Full Text Available Corneal transparency is the basis of the normal physiological functions.However, corneal neovascularization(CNVmay occur in the infection, mechanical and chemical injury or under other pathological conditions,which make the cornea lose original transparency and severe visual impairment. In recent years, along with the development of immunology, molecular biology, biochemistry and other disciplines, there is more in-depth understanding on the CNV, and clinical treatment of CNV has made new breakthroughs. This article provides an overview of the inhibition of CNV.

Differentiation of mild keratoconus from corneal warpage according to topographic inferior steepening based on corneal tomography data

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Lia Florim Patrão

Full Text Available ABSTRACT We report two cases of suspicious asymmetric bow tie and inferior steepening on topographic evaluations with reflection (Placido and projection (Scheimpflug. Rotating Scheimpflug corneal and anterior segment tomography (Oculus Pentacam HR, Wetzlar, Germany® was performed in the first case, with a maximal keratometric value (Kmax of 43.2 D and an overall deviation value from the Belin/Ambrósio Enhanced Ectasia Display (BAD-D of 1.76, which was observed in the study eye (OD. BAD-D was 6.59 in the fellow eye, which had clinical findings that were consistent with keratoconus stage 2. The second case presented with a Kmax of 45.3 D and BAD-D of 0.76 in OD and 1.01 in OS. This patient had discontinued wearing soft contact lens less than 1 day prior to examination. Corneal tomographic data enabled us to distinguish mild or forme fruste keratoconus from contact lens-induced corneal warpage, and similar findings were observed on curvature maps.

Dynamic ultra high speed Scheimpflug imaging for assessing corneal biomechanical properties

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Renato Ambrósio Jr

2013-04-01

Full Text Available OBJECTIVE: To describe a novel technique for clinical characterization of corneal biomechanics using non-invasive dynamic imaging. METHODS: Corneal deformation response during non contact tonometry (NCT is monitored by ultra-high-speed (UHS photography. The Oculus Corvis ST (Scheimpflug Technology; Wetzlar, Germany has a UHS Scheimpflug camera, taking over 4,300 frames per second and of a single 8mm horizontal slit, for monitoring corneal deformation response to NCT. The metered collimated air pulse or puff has a symmetrical configuration and fixed maximal internal pump pressure of 25 kPa. The bidirectional movement of the cornea in response to the air puff is monitored. RESULTS: Measurement time is 30ms, with 140 frames acquired. Advanced algorithms for edge detection of the front and back corneal contours are applied for every frame. IOP is calculated based on the first applanation moment. Deformation amplitude (DA is determined as the highest displacement of the apex in the highest concavity (HC moment. Applanation length (AL and corneal velocity (CVel are recorded during ingoing and outgoing phases. CONCLUSION: Corneal deformation can be monitored during non contact tonometry. The parameters generated provide clinical in vivo characterization of corneal biomechanical properties in two dimensions, which is relevant for different applications in Ophthalmology.

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

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Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

2017-06-01

We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Evaluation of corneal changes after myopic LASIK using the Pentacam®

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Khairat YM

2013-09-01

Full Text Available Yehia M Khairat, Yasser H Mohamed, Ismail ANO Moftah, Narden N Fouad Department of Ophthalmology, Faculty of Medicine, El-Minya University, Egypt Background: In this study, we used a Pentacam® device to evaluate the corneal changes that occur after laser-assisted in situ keratomileusis (LASIK. Methods: Our study included 60 eyes of 32 patients. All patients were treated for myopia and myopic astigmatism using LASIK. The eyes were examined preoperatively and 3 months postoperatively using a Pentacam to assess corneal changes with regard to curvature, elevation, and asphericity of the cornea. Results: A statistically significant decrease in mean keratometric power of the anterior corneal surface (P = 0.001 compared with its pre-LASIK value was detected after 3 months, but there was no significant change in keratometric power of the posterior surface (P = 0.836. Asphericity (Q-value of the anterior and posterior surfaces increased significantly after LASIK (P = 0.001. A significant forward bulge of the anterior corneal surface 4 mm and 7 mm from the central zone was detected 3 months post-LASIK (P = 0.001 for both, but there was no significant increase in posterior elevation at 4 mm and 7 mm from the center (P = 0.637 and P = 0.26, respectively. No cases of post-LASIK ectasia were detected. Correlation between different parameters of the corneal surface revealed an indirect relation between changes in pachymetry and anterior corneal elevation at 4 mm and 7 mm from the central zone (r = −0.27, P = 0.13, and r = −0.37, P = 0.04, respectively, and a direct proportion between changes in pachymetry and mean keratometric power of the anterior and posterior corneal surfaces (r = 0.7, P = 0.001 and r = 0.4, P = 0.028, respectively. Conclusion: LASIK causes significant changes at the anterior corneal surface but the effect is subtle and insignificant at the posterior surface. Keywords: LASIK, laser-assisted in situ keratomileusis, Pentacam®, corneal

A Clinical Microbiological Study of Corneal Ulcer Patients at Western Gujarat, India

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Nilesh Dhanjibhai Patel

2013-06-01

Full Text Available Corneal ulcer is a major cause of blindness throughout the world. When the cornea is injured by foreign particles, there are chances of infection by the organism and development of ulcer. Bacterial infection in the cornea is invariably an alteration of the defense mechanism of the outer eye. It is essential to determine the local etiology within a given region when planning a corneal ulcer management strategy. Laboratory evaluation is necessary to establish the diagnosis and to guide the antibiotic therapy. One hundred corneal ulcer patients were studied by collecting their corneal scraping samples and processing at Clinical Microbiology department of Shree Meghaji Petharaj Shah Medical College, Jamnagar, Gujarat, India during a period of 17 months. All clinical microbiology laboratory procedures followed standard protocols described in the literature. 40 (40% patients from the age group of 20-70 years had been confirmed as - any organism culture positive - within the corneal ulcer patient population. Fungi were isolated from 26 (26% corneal ulcer patients. The bacterial etiology was confirmed in 14 (14% corneal ulcer patients. The major risk factors for mycotic keratitis were vegetative injury (16, (62%, followed by conjunctivitis (4, (15%, and blunt trauma (3, (11%. Pseudomonas aeruginosa was the most commonly isolated bacterium (6, (43%, followed by Proteus spp. (4, (29%. Corneal Infections due to bacteria and filamentous fungi are a frequent cause of corneal damage. Microbiological investigation is an essential tool in the diagnosis of these infections. The frequency of fungal keratitis has risen over the past 20 to 30 years. Prognosis of bacterial corneal infection has improved since the introduction of specific antibacterial therapy.

A clinical microbiological study of corneal ulcer patients at western Gujarat, India.

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Rajesh Somabhai Katara

2013-06-01

Full Text Available Corneal ulcer is a major cause of blindness throughout the world. When the cornea is injured by foreign particles, there are chances of infection by the organism and development of ulcer. Bacterial infection in the cornea is invariably an alteration of the defense mechanism of the outer eye. It is essential to determine the local etiology within a given region when planning a corneal ulcer management strategy. Laboratory evaluation is necessary to establish the diagnosis and to guide the antibiotic therapy. One hundred corneal ulcer patients were studied by collecting their corneal scraping samples and processing at Clinical Microbiology department of Shree Meghaji Petharaj Shah Medical College, Jamnagar, Gujarat, India during a period of 17 months. All clinical microbiology laboratory procedures followed standard protocols described in the literature. 40 (40% patients from the age group of 20-70 years had been confirmed as - any organism culture positive - within the corneal ulcer patient population. Fungi were isolated from 26 (26% corneal ulcer patients. The bacterial etiology was confirmed in 14 (14% corneal ulcer patients. The major risk factors for mycotic keratitis were vegetative injury (16, (62%, followed by conjunctivitis (4, (15%, and blunt trauma (3, (11%. Pseudomonas aeruginosa was the most commonly isolated bacterium (6, (43%, followed by Proteus spp. (4, (29%. Corneal Infections due to bacteria and filamentous fungi are a frequent cause of corneal damage. Microbiological investigation is an essential tool in the diagnosis of these infections. The frequency of fungal keratitis has risen over the past 20 to 30 years. Prognosis of bacterial corneal infection has improved since the introduction of specific antibacterial therapy.

Corneal complications and visual impairment in vernal keratoconjunctivitis patients

International Nuclear Information System (INIS)

Arif, A.S.; Aaqil, B.; Siddiqui, A.; Nazneen, Z.; Farooq, U.

2017-01-01

Vernal kerato-conjunctivitis (VKC) is an infrequent but serious form of allergic conjunctivitis common in warm and humid areas where air is rich in allergens. It affects both eyes asymmetrically. Although VKC is a self-limiting disease but visions affecting corneal complications influence the quality of life in school children. The aim of this study was to list the corneal complications due to this condition and to find out the extent of visual impairment among VKC patients. Methods: This cross-sectional study was conducted in the department of Ophthalmology, Benazir Bhutto Shaheed Hospital on 290 eyes of diagnosed cases of VKC. The diagnosis of VKC was made on the basis of history and examination. Visual acuity was recorded using Snellen's notation and visual impairment was classified according to World Health Organization classification for visual disabilities. Results: The mean age of presentation was 10.83+-6.13 years. There were 207 (71.4%) males and 83 (28.6%) females. Corneal scarring was observed in 59 (20.3%) eyes. Keratoconus was found to be in 17 (5.9%) eyes. Shield ulcer was detected in 09 (3.1%) eyes while 07 (2.4%) eyes had corneal neovascularization. Majority of the patients with visual loss had corneal scarring and the complication that led to severe visual loss in most of the eyes was Keratoconus. Conclusion: Vernal kerato-conjunctivitis in the presence of corneal complications is a sight threatening disease and can lead to severe visual impairment. (author)

Corneal biomechanical properties after laser-assisted in situ keratomileusis and photorefractive keratectomy

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Hwang ES

2017-10-01

Full Text Available Eileen S Hwang,1 Brian C Stagg,1 Russell Swan,1 Carlton R Fenzl,1 Molly McFadden,2 Valliammai Muthappan,1 Luis Santiago-Caban,1 Mark D Mifflin,1 Majid Moshirfar1,3 1Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 2Department of Internal Medicine, University of Utah, Salt Lake City, 3HDR Research Center, Hoopes Vision, Draper, UT, USA Background: The purpose of this study was to evaluate the effects of laser-assisted in situ keratomileusis (LASIK and photorefractive keratectomy (PRK on corneal biomechanical properties.Methods: We used the ocular response analyzer to measure corneal hysteresis (CH and corneal resistance factor (CRF before and after refractive surgery.Results: In all, 230 eyes underwent LASIK and 115 eyes underwent PRK without mitomycin C (MMC. Both procedures decreased CH and CRF from baseline. When MMC was used after PRK in 20 eyes, it resulted in lower corneal biomechanical properties at 3 months when compared to the other procedures, but all three procedures had similar values at 12 months.Conclusion: Significant but similar decreases in corneal biomechanical properties after LASIK, PRK without MMC, and PRK with MMC were noted. Keywords: corneal biomechanics, photorefractive keratectomy, laser-assisted in situ keratomileusis, corneal hysteresis, corneal resistance factor, mitomycin C

Changes in corneal sensitivity following cross-linking for progressive early-stage keratoconus

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Anelise de Medeiros Lago

2014-04-01

Full Text Available Purpose: To evaluate changes in corneal sensitivity following corneal cross-linking (CXL in patients with progressive earlier stage keratoconus. Methods: Thirty-eight eyes of 19 patients (11 women, 8 men were included in a prospective, nonrandomized clinical study. The mean patient age was 22 years (range, 18-26 years. Inclusion criteria were early stage bilateral progressive keratoconus, a transparent cornea, and a thickness of ≥440 µm in the thinnest area of the cornea. Using the Cochet-Bonnet esthesiometer, central corneal sensitivity was measured before surgery, 7 days after surgery, and once a month thereafter until recovery of baseline preoperative levels. Central corneal sensitivity >40 mm was considered normal. Results: Corneal sensitivity gradually returned to preoperative levels in all treated eyes. The mean central corneal sensitivity was 52.2, 24.0, 38.2, 42.5, 50.0, and 52.5 mm before surgery, 7 days after surgery, and at 1, 2, 3, and 4 months after surgery, respectively. Normal levels of corneal sensation, but not baseline (preoperative levels, were observed 2 months after surgery. The preoperative levels were observed 3 months after surgery. Conclusions: Our results suggest that central corneal sensitivity can be decreased for as long as 3 months after CXL for progressive earlier stage keratoconus.

Effect of corneal inhomogeneity on the mechanical behavior of the eye

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Stein, A. A.; Moiseeva, I. N.

2018-05-01

The effect of spatial inhomogeneity of the effective cornea stiffness distribution on the mechanical properties of the eye is investigated on the basis of the two-component model of the eyeball, in which the cornea is represented by a momentless deformable, linearly elastic surface and the scleral region by an elastic element that responds to changes in intraocular pressure by changes in volume. The approach used makes it possible to consider within the same model both the natural corneal inhomogeneity and mechanical consequences of local cornea weakening owing to surgical procedures. The dependences on changes in intraocular pressure of parameters that characterize deformation properties of both the cornea (apex displacement) and the eyeball as a whole (change in intraocular volume) are obtained. For moderate inhomogeneity they differ from the same dependences for the homogenous cornea with effective stiffness equal to the average value for the corresponding inhomogeneous distribution only slightly. However, if the effective stiffness amplitude is very high, corneal inhomogeneity discernibly affects the integral response of the cornea and the eyeball as a whole to changes in pressure. The effect of inhomogeneity on the data of tonometry also mainly depends on the average effective corneal stiffness. The difference between the tonometric and true pressures increases with surgical cornea weakening in the apical region for both Schiøtz and Maklakoff tonometers.

A Rare Form of Corneal Opacity Associated with Spondyloepiphyseal Dysplasia Congenita

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Yuichiro Ishida

2018-02-01

Full Text Available A 13-year-old Japanese female diagnosed with spondyloepiphyseal dysplasia congenita (SEDC was referred for ophthalmologic evaluation. Examination with slit-lamp and optical coherence tomography revealed bilateral thin cornea with diffuse corneal opacity which was localised at the posterior stromal depth in the central cornea. Unlike the two previously reported cases of diffuse and nodular patterns of corneal opacity in SEDC, the current case exhibited a rare form of corneal opacity. SEDC is one of the type II collagenopathies, characterised by dwarfism because the mutations in COL2A1 prevent bone growth. Although the existence of type II collagen has not been reported in the human corneal stroma, the aetiology of the opacity in the corneal stroma in SEDC type II collagenopathy is of interest.

Femtosecond laser-assisted keratoplasty in a child with corneal opacity:case report

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E. Yu. Markova

2014-01-01

Full Text Available Corneal opacities are the fourth cause of blindness world-wide. Over the past two centuries, various corneal transplantation (i.e., keratoplasty methods have been developed and improved. Nowadays, femtolaserssisted keratoplasty is one of most promising techniques. Femtosecond laser have several advantages that provide additional surgical benefits. Among them, no thermal injury, the ability to cut deeply on a single plane and to perform various corneal profiles should be mentioned. In children, corneal disorders are of special importance while femtosecondassisted keraatoplasty case reports are rare. Here, we describe femtosecond laserssisted penetrating keratoplasty in a girl with a rough central corneal opacity.

Edge detection and mathematic fitting for corneal surface with Matlab software.

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Di, Yue; Li, Mei-Yan; Qiao, Tong; Lu, Na

2017-01-01

To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax 2 +Bx+C), Polynomial curve [p(x)=p1x n +p2x n-1 +....+pnx+pn+1] and Conic section (Ax 2 +Bxy+Cy 2 +Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t -test. Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc . There were no significant differences between 'e' values by corneal topography and conic section ( t =0.9143, P =0.3760 >0.05). It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties.

Decerebrate mouse model for studies of the spinal cord circuits

DEFF Research Database (Denmark)

Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin

2017-01-01

The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....

Topical Administration Is a Promising Inoculating Route versus Intramuscular Inoculation for the Nanoparticle-Carried DNA Vaccine to Prevent Corneal Infections.

Science.gov (United States)

Hu, Kai; Malla, Tejsu; Zhai, Yujia; Dong, Lili; Tang, Ru

2015-01-01

To evaluate the comparative effect of topical versus intramuscular administration of nanoparticle-carried DNA vaccine in preventing corneal herpes simplex virus type 1 (HSV-1) infection. Nanoparticle [polyethylenimine (PEI)-Fe3O4]-carried DNA vaccine (PEI-Fe3O4-pRSC-gD-IL-21) or DNA vaccine (pRSC-gD-IL-21) alone were topically versus intramuscularly inoculated into one eye each of mice on days 0, 14 and 28. Three weeks after the final immunization, the specific immune responses and clinical degrees of primary herpes simplex keratitis were evaluated. Topical inoculation of nanoparticle-carried DNA vaccine induced mice to generate similar levels of specific HSV-1-neutralizing antibody, IFN-γ and IL-4 in serum and specific killing (cytotoxicity) and proliferative activities of the splenic lymphocytes, but a significantly higher level of secretory IgA in tears compared to those of intramuscular inoculation. More importantly, the mice inoculated topically showed a significantly decreased herpes simplex keratitis severity than the mice inoculated intramuscularly after HSV-1 challenge on the corneas of the mice. Topical inoculation of nanoparticle-carried DNA vaccine elicits a stronger specific local immune response and more effectively inhibits herpes simplex keratitis as compared to intramuscular inoculation in an HSV-1 ocular challenge mouse model. Thus, topical administration may be a promising inoculating route for the nanoparticle-carried DNA vaccine to prevent corneal infections. © 2015 S. Karger AG, Basel.

Infiltrados corneales asociados al uso de lentes de contacto Corneal infiltrates associated with contact lens wear

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Vivian Padrón Álvarez

2001-12-01

Full Text Available Se estudiaron 15 pacientes que usan lentes de contacto rígidas, permeables al gas (LCRPG y lentes de contacto blandas (LCB que presentaron infiltrados corneales. Se realizó estudio microbiológico de las lesiones y seguimiento clínico de estos casos. En 3 de los casos estudiados el cultivo fue positivo a estafilococo aureus, el resto de los estudios microbiológicos fueron negativos. Todos los pacientes respondieron rápidamente al retirar la lente de contacto y al tratamiento con antibióticos tópicos y ninguno tuvo afectación permanente de la agudeza visual. El diagnóstico exacto y el manejo apropiado de los infiltrados corneales en pacientes que usan lentes de contacto es de gran importancia por la posibilidad de infección o de secuela visual permanente.15 patients wearing gas permeable rigid contact lenses (GPRCL and soft contanct lenses (SCL that presented corneal infiltrates were studied. A microbiological study of the injuries and a clinical follow-up of these cases were conducted. In 3 of the studied cases the culture was positive to Staphyloccocus aureus. The rest of the mircobiological studies were negative. All the patients responded rapidly to the contact lens removal and to the treatment with topical antibiotics. None of them had permanent affection of visual acuity. The accurate diagnosis and the appropiate management of the corneal infiltrates in patients wearing contact lenses is very important due to the possibility of infection or of permanent visual sequela.

The application of excimer lasers for corneal sculpturing

International Nuclear Information System (INIS)

King, M.C.

1990-01-01

Of the broad selection of lasers available for surgery, the argon fluoride excimer laser offers a set of attributes that make it uniquely suited for the removal of corneal tissue. With ultraviolet radiation at 193mm, the energy of an individual photon (6.3 electron volts) is sufficient to break bonds in protein molecules without generating molecular vibration (heat). A single laser pulse is capable of removing 0.25 microns of corneal tissue over a well defined area 80 mm 2 in extent. This excision with a lateral precision to a fraction of a micron causes no discernible damage to neighboring cells. The smooth surface left after the tissue is removed promotes a quick and predictable regrowth of the epithelium. The penetration of radiation into the underlying tissue is the order of a micron so there is no potential harm to the lens or retinal tissue. Insignificant mutagenesis or unscheduled DNA synthesis has been detected as a result of tissue irradiation at this wavelength. In the past few years major progress has been made towards developing ophthalmic procedures which utilize the unique properties of this laser. To date there are FDA IDE's (Investigational Device Exemptions) for the following procedures: Photorefractive Keratectomy (PRK) or corneal reshaping for correcting near-sightedness, far-sightedness and astigmatism without the need for eye glasses, contact lenses or conventional refractive surgery (Radial Keratotomy); Partial Excimer Trabeculectomy for relieving the pressure build-up caused by glaucoma; T-Excisons for reducing astigmatism; Myopic Keratomileusis (MKM) for the refractive correction of severe myopia; superficial Keratectomy (corneal smoothing) for treating various corneal scars, dystrophies, recurrent corneal erosion etc. In this paper the fundamentals of beam tissue interaction at 193nm will be discussed

21 CFR 886.1450 - Corneal radius measuring device.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal radius measuring device. 886.1450 Section 886.1450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... corneal size by superimposing the image of the cornea on a scale at the focal length of the lens of a...

Corneal-Wavefront guided transepithelial photorefractive keratectomy after corneal collagen cross linking in keratoconus

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Massimo Camellin

2017-01-01

Conclusions: Corneal-Wavefront guided transepithelial PRK ablation profiles after conventional CXL yields to good visual, optical, and refractive results. These treatments are safe and efficacious for the correction of refracto-therapeutic problems in keratoconic patients.

Amniotic membrane extract ameliorates benzalkonium chloride-induced dry eye in a murine model.

Science.gov (United States)

Xiao, Xinye; Luo, Pingping; Zhao, Hui; Chen, Jingyao; He, Hui; Xu, Yuxue; Lin, Zhirong; Zhou, Yueping; Xu, Jianjiang; Liu, Zuguo

2013-10-01

Human amniotic membrane (AM) is avascular but contains various beneficial bioactive factors, its extract (AE) is also effective in treating many ocular surface disorders. In this study, we for the first time evaluated the therapeutic effects of AE on dry eye induced by benzalkonium chloride in a BALB/c mouse model. Topical application of AE (1.5 and 3 μg/eye/day) resulted in significantly longer tear break-up time on Day 3 and 6, lower fluorescein staining scores on Day 3, and lower inflammatory index on Day 6. AE reduced corneal epithelial K10 expression, inflammatory infiltration, and levels of TNF-α, IL-1β and IL-6 in BAC treated mice than that in the control mice. Moreover, decreased TUNEL positive cells in cornea and increased goblet cells in conjunctiva were also observed in AE treated corneas. Finally, AE induced more Ki-67 positive cells in corneal epithelium of dry eye mouse. Taken together, our data provide further support for BAC induced dry eye model as a valuable for dry eye study and suggest a great potential for AE as a therapeutic agent in the clinical treatment of dry eye. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Event Coordination Notation: Behaviour Modelling Beyond Mickey Mouse

DEFF Research Database (Denmark)

Jepsen, Jesper; Kindler, Ekkart

2015-01-01

The Event Coordination Notation (ECNO) allows modelling the desired behaviour of a software system on top of any object-oriented software. Together with existing technologies from Model-based Software Engineering (MBSE) for automatically generating the software for the structural parts, ECNO allows...... special aspect of ECNO or another; and it would be fair to call them “Mickey Mouse examples”. In this paper, we give a concise overview of the motivation, ideas, and concepts of ECNO. More importantly, we discuss a larger system, which was completely generated from the underlying models: a workflow...... management system. This way, we demonstrate that ECNO can be used for modelling software beyond the typical Mickey Mouse examples. This example demonstrates that the essence of workflow management – including its behaviour – can be captured in ECNO: in a sense, it is a domain model of workflow management...

Evaluation of keratoconus in Asians: role of Orbscan II and Tomey TMS-2 corneal topography.

Science.gov (United States)

Lim, Li; Wei, Rui Hua; Chan, Wing Kwong; Tan, Donald T H

2007-03-01

To evaluate the corneal topographic patterns of Asian patients with keratoconus (KC). Prospective observational case-control study. Institutional. A total of 116 patients (both eyes included) with KC were recruited. The control group consisted of 70 laser in-situ keratomileusis (LASIK) candidates with myopia. Patients with previous ocular surgery and trauma were excluded. Corneal topography was performed using the Tomey KC screening system (Topographic Modeling System, software version 2.4.2J, Tomey Corp, Nagoya, Japan) and Orbscan II corneal topography system (Bausch & Lomb Surgical, Orbtek Inc, Salt Lake City, Utah, USA). Videokeratographic variables were analyzed and the eyes were grouped into KC, KC suspect, and control groups. The corneal topographic patterns of 196 eyes were analyzed. The topographic patterns displayed by Tomey (TMS-2N) and Orbscan II were similar. The majority of eyes with KC (71.2%) and KC suspect (70%) had asymmetric bowtie patterns. Thirteen indices of TMS-2N were analyzed and the means of the indices were found to be significantly higher in eyes in the KC group than the KC suspect group (P TMS-2N.

Comparison of Changes in Central Corneal Thickness During Corneal Collagen Cross-Linking, Using Isotonic Riboflavin Solutions With and Without Dextran, in the Treatment of Progressive Keratoconus.

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Zaheer, Naima; Khan, Wajid Ali; Khan, Shama; Khan, M Abdul Moqeet

2018-03-01

To compare intraoperative changes in central corneal thickness (CCT) during corneal cross-linking, using 2 different isotonic riboflavin solutions either with dextran or with hydroxy propyl methylcellulose, in the treatment of progressive keratoconus. In this retrospective study, we analyzed records of corneal thickness measurements, taken during various steps of cross-linking. Cross-linking was performed using either isotonic riboflavin with dextran (group A) or isotonic riboflavin with hydroxy propyl methylcellulose (without dextran) (group B). CCT measurements were recorded before and after epithelial removal, after saturation with respective isotonic riboflavin solution, after use of hypotonic riboflavin in selected cases, and after ultraviolet A (UV-A) application. A mixed-way analysis of variance was conducted on CCT readings within each group and between both groups, and p dextran causes a significant decrease in corneal thickness, whereas dextran-free isotonic riboflavin causes a significant increase in corneal thickness, thus facilitating the procedure.

Effect of the Regenerative Agent Poly(Carboxymethylglucose Sulfate) on Corneal Wound Healing After Corneal Cross-Linking for Keratoconus.

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Kymionis, George D; Liakopoulos, Dimitrios A; Grentzelos, Michael A; Tsoulnaras, Konstantinos I; Detorakis, Efstathios T; Cochener, Béatrice; Tsilimbaris, Miltiadis K

2015-08-01

To evaluate the effect of a regenerative agent (RGTA) [Cacicol20-poly(carboxymethyl glucose sulfate); OTR3, Paris, France] on corneal reepithelialization and pain after corneal cross-linking (CXL) for keratoconus. In this prospective comparative (contralateral) clinical study, patients with bilateral progressive keratoconus underwent CXL treatment. The corneal epithelium during CXL was removed using transepithelial phototherapeutic keratectomy (Cretan protocol). One eye of each patient was randomly instilled with an RGTA (Cacicol20) once a day (study group), whereas the fellow eye was instilled with artificial tears (control group). Patients were examined daily until complete reepithelialization. Postoperative examinations included slit-lamp biomicroscopy to assess the epithelial defect size and subjective evaluation of pain. The study enrolled 18 patients (36 eyes). The mean epithelial defect size for study and control groups was 19.6 ± 4.2 mm versus 21.5 ± 2.8 mm, respectively, at day 1 (P = 0.019) and 6.4 ± 3.4 mm versus 7.9 ± 4.3 mm, respectively, at day 2 (P = 0.014). At day 3 postoperatively, 61.1% of study eyes were fully reepithelialized, compared with 11.1% of control eyes (P = 0.002). RGTA (Cacicol20) instillation seems to result in faster corneal reepithelialization after CXL in this study. However, there was no significant effect in subjective pain/discomfort.

Transplantation with cultured stem cells derived from the human amniotic membrane for corneal alkali burns: an experimental study.

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Zeng, Wei; Li, Yanwei; Zeng, Guangwei; Yang, Bo; Zhu, Yu

2014-01-01

Amniotic membranes (AM) have been used in a wide range of clinical applications. We successfully extracted mesenchymal stem cells (MSCs) from human AM, but little is known about the use and efficacy of human amniotic membrane-derived mesenchymal stem cells (hAM-dMSCs) for the treatment of alkali burns. We utilized hAM-dMSCs transplantation, AM grafting, and their combined use in the treatment of alkali burns. An experimental model in rabbits was devised to analyze the use of these techniques with immunocytochemistry and ELISA. The survival and migration of hAM-dMSCs labeled by SPION in the host were assessed with Prussian blue staining. Compared with the control group, the treated groups demonstrated faster reconstruction of the corneal epithelium, and lower levels of corneal opacification and neovascularization within corneal alkali burns. Furthermore, dark blue-stained particles were detected in the limbus corneae at day 28. These results demonstrated the ability of hAM-dMSCs to enhance epithelial healing and reduce corneal opacification and neovascularization in corneal alkali wounds.

Chronic pesticide exposure and consequential keratectasia & corneal neovascularisation.

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Sanyal, Shalini; Law, Atrayo; Law, Sujata

2017-11-01

Ocular toxicity as a consequence of chronic pesticide exposure is one of the health hazards caused due to extended exposure to pesticides. The cornea, due to its position as the outer ocular layer and its role in protecting the internal layers of the eye; is gravely affected by this xenobiotic insult to the eye, leading to ocular irritation and damage to normal vision. The deleterious effects of chronic pesticide exposure on the various corneal layers and the ocular risks involved therein, were explored by mimicking the on-field scenario. Cytological, histological and flowcytometric parameters were taken into consideration to determine the enhanced risk of corneal neovascularisation and keratectasia, specifically, keratoconus. Chronic exposure to pesticides leads to heightened ocular morbidity wherein there were visible pathophysiological changes to the ocular surface. The cornea was found to be adversely affected with visible protuberance in a cone-like shape, characteristic of keratoconus in a majority of the experimental animals. Further analyses revealed a detrimental impact on all the corneal layers and an amplified expression of inflammation markers such as TNF-α, VCAM-1 and ICAM-1. Additionally, it was found that post pesticide exposure, the corneal surface developed hypoxia, leading to a significant increase of angiogenesis promoting factors and consequential neovascularisation. Apart from ocular toxicity, chronic exposure to pesticides significantly increases the risks of keratectasia and corneal neovascularisation; disorders which lead to diminished vision and if untreated, blindness. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy

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Yun Gu

2014-01-01

Full Text Available Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK. The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ, GSK3787 (a selective antagonist of PPARδ, or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin and ECM production (fibronectin, collagen type III and collagen type I were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.

Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization

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Yukako Taketani

2016-01-01

Full Text Available Corneal neovascularization (CNV is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2 is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV.

Derivation of corneal endothelial cell-like cells from rat neural crest cells in vitro.

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Chengqun Ju

Full Text Available The aim of this study was to investigate the feasibility of inducing rat neural crest cells (NCC to differentiate to functional corneal endothelial cell (CEC-like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used to detect expression of the corneal endothelium differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were transplanted to the corneal endothelium of a rat corneal endothelium deficiency model, and an eye-down position was maintained for 24 hours to allow cell attachment. The animals were observed for as long as 2 months after surgery and underwent clinical and histological examination. Spindle-like NCC turned to polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula occludens-1 and sodium-potassium pump Na(+/K(+ ATPase. The corneas of the experimental group were much clearer than those of the control group and the mean corneal thickness in the experimental group was significantly less than in the control group7, 14, 21 and 28 days after surgery. Confocal microscopy through focusing and histological analysis confirmed that green fluorescence-positive CEC-like cells formed a monolayer covering the Descemet's membrane in the experimental group. In conclusion, CEC-like cells derived from NCCs displayed characters of native CEC, and the induction protocol provides guidance for future human CEC induction from NCC.

Corneal Graft Rejection: Incidence and Risk Factors

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Alireza Baradaran-Rafii

2008-12-01

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PURPOSE: To determine the incidence and risk factors of late corneal graft rejection after penetrating keratoplasty (PKP. METHODS: Records of all patients who had undergone PKP from 2002 to 2004 without immunosuppressive therapy other than systemic steroids and with at least one year of follow up were reviewed. The role of possible risk factors such as demographic factors, other host factors, donor factors, indications for PKP as well as type of rejection were evaluated. RESULTS: During the study period, 295 PKPs were performed on 286 patients (176 male, 110 female. Mean age at the time of keratoplasty was 38±20 (range, 40 days to 90 years and mean follow up period was 20±10 (range 12-43 months. Graft rejection occurred in 94 eyes (31.8% at an average of 7.3±6 months (range, 20 days to 39 months after PKP. The most common type of rejection was endothelial (20.7%. Corneal vascularization, regrafting, anterior synechiae, irritating sutures, active inflammation, additional anterior segment procedures, history of trauma, uncontrolled glaucoma, prior graft rejection, recurrence of herpetic infection and eccentric grafting increased the rate of rejection. Patient age, donor size and bilateral transplantation had no significant influence on graft rejection. CONCLUSION: Significant risk factors for corneal graft rejection include

Corneal erosions, bacterial contamination of contact lenses, and microbial keratitis.

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Willcox, Mark D P; Naduvilath, Thomas J; Vaddavalli, Pravin K; Holden, Brien A; Ozkan, Jerome; Zhu, Hua

2010-11-01

To estimate the rate of corneal erosion coupled with gram-negative bacterial contamination of contact lenses and compare this with the rate of microbial keratitis (MK) with contact lenses. The rate of corneal erosion and contact lens contamination by gram-negative bacteria were calculated from several prospective trials. These rates were used to calculate the theoretical rate of corneal erosion happening at the same time as wearing a contact lens contaminated with gram-negative bacteria. This theoretical rate was then compared with the rates of MK reported in various epidemiological and clinical trials. Corneal erosions were more frequent during extended wear (0.6-2.6% of visits) compared with daily wear (0.01-0.05% of visits). No corneal erosions were observed for lenses worn on a daily disposable basis. Contamination rates for lenses worn on a daily disposable basis were the lowest (2.4%), whereas they were the highest for low Dk lenses worn on an extended wear basis (7.1%). The estimated rate of corneal erosions occurring at the same time as wearing lenses contaminated with gram-negative bacteria was the lowest during daily wear of low Dk lenses (1.56/10,000 [95% CI: 0.23-10.57]) and the highest during extended wear of high Dk lenses (38.55/10,000 [95% CI: 24.77-60.04]). These rates were similar in magnitude to the rates reported for MK of different hydrogel lenses worn on differing wear schedules. The coincidence of corneal erosions during lens wear with gram-negative bacterial contamination of lenses may account for the relative incidence of MK during lens wear with different lens materials and modes of use.

Síndrome erosivo corneal recurrente enmascarado como queratitis epitelial herpética

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Manuel A. de Alba-Castilla

2015-10-01

Conclusiones: Los rasgos distintivos del SECR son: inicio abrupto por la noche o madrugada al despertar, antecedente de trauma corneal o distrofia corneal anterior y ausencia de leucomas corneales. La semejanza sintomatológica y el desconocimiento del SECR incrementan la posibilidad de confundir el diagnóstico.

Evaluation of central and peripheral corneal thicknesses in patients with rheumatoid arthritis

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Alime Gunes

2015-08-01

Full Text Available ABSTRACTPurpose:To evaluate central corneal thickness (CCT and peripheral corneal thickness (PCT in patients with rheumatoid arthritis (RA and to assess the relationships among the corneal parameters, dry eye disease, and clinical variables of RA.Methods:A total of 58 RA patients and 58 control subjects participated in this study. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was performed using Schirmer’s test, tear break-up time (TBUT, corneal fluorescein staining, and Ocular Surface Disease Index (OSDI. Corneal thickness at the apex point, the center of the pupil, the thinnest point, and PCT (3 mm from the apex to the superior, inferior, nasal, and temporal locations were evaluated using Scheimpflug imaging (Pentacam®. Additionally, the relative peripheral index (RPI was calculated by dividing the PCT by the CCT. The disease severity and quality of life were evaluated with DAS28 and HAQ, respectively. The laboratory evaluation comprised ESR and CRP.Results:The mean corneal thicknesses at the apex point, the center of the pupil, the thinnest point, and the superior, inferior, nasal, and temporal points were significantly thinner in RA patients than controls. Schirmer’s test scores and TBUT were significantly lower, and corneal staining and OSDI scores were significantly higher in RA patients. There were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.Conclusion:The CCT and PCT were thinner in RA patients compared to those in control subjects. However, there were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests.

Management of Corneal Bee Sting Injuries.

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Rai, Ruju R; Gonzalez-Gonzalez, Luis A; Papakostas, Thanos D; Siracuse-Lee, Donna; Dunphy, Robert; Fanciullo, Lisa; Cakiner-Egilmez, Tulay; Daly, Mary K

2017-01-01

To review the management of keratitis after corneal bee stings and to report a case of deep stromal corneal infiltrate secondary to a retained bee stinger managed conservatively in a patient who presented three days after unsanitary manipulation of the stinger apparatus. Case report and review of literature. A 57-year-old male beekeeper was evaluated for pain, blurry vision, and photosensitivity after a corneal bee sting. Of note, the venom sac had been removed with dirty tweezers three days prior to his visit. On exam, a focal infiltrate with diffuse edema was seen surrounding a retained bee stinger in the peripheral cornea. Trace cells in the anterior chamber were also noted. Based on a high suspicion for infectious keratitis, a conservative treatment strategy was elected. Administration of broad-spectrum topical antibiotics with concomitant abstention of corticosteroids led to rapid resolution of the symptoms. Over 16 months of follow-up, the stinger has remained in situ without migration and the patient has maintained 20/20 visual acuity without complications. There is debate on the preferred method for the management of corneal injury secondary to bee stings, especially when it is associated with a retained stinger. We herein present our findings in our appraisal of reported cases. In the aftermath of an ocular bee sting, close surveillance for inflammation and infection is essential. Individual manifestations of these injuries vary in timing, type, and severity; therefore, the accessibility of the stinger and the evolving clinical picture should guide therapeutic decisions.

Pathology of Mouse Models of Accelerated Aging

NARCIS (Netherlands)

Harkema, L.; Youssef, S. A.; de Bruin, A.

Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience,

Pathology of Mouse Models of Accelerated Aging

NARCIS (Netherlands)

Harkema, L; Youssef, S A; de Bruin, A

2016-01-01

Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

Conjunctival-corneal melt in association with carotid artery stenosis

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Rosalind MK Stewart

2008-10-01

Full Text Available Rosalind MK Stewart1, Say Aun Quah1, Dan Q Nguyen2, Stephen B Kaye11Royal Liverpool University Hospital, Liverpool, UK; 2Bristol Eye Hospital, Bristol, UKPurpose: To report a case of severe conjunctival-corneal melt in association with carotid artery stenosis.Methods: Observational case report.Results: A 76-year-old man with a history of bilateral severe carotid artery occlusion and nonarteritic ischemic optic neuropathy developed a spontaneous bulbar conjunctival defect. Despite intensive lubrication, and attempts at surgical closure including an amniotic membrane patch graft, it progressed with subsequent adjacent corneal perforation. Thorough investigations revealed no underlying disease, except markedly delayed episcleral vessel filling on anterior segment fluorescein angiography.Conclusions: Neovascularisation is a known factor in the inhibition of ulceration. In light of the findings in this report, ocular ischemia should be considered as a cause or contributing factor in the differential diagnosis of conjunctival-corneal melt.Keywords: conjunctival melt, corneal melt, ocular ischemia, carotid artery stenosis

Keratoprostheses for corneal blindness: a review of contemporary devices

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Avadhanam, Venkata S; Smith, Helen E; Liu, Christopher

2015-01-01

According to the World Health Organization, globally 4.9 million are blind due to corneal pathology. Corneal transplantation is successful and curative of the blindness for a majority of these cases. However, it is less successful in a number of diseases that produce corneal neovascularization, dry ocular surface and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only alternative to restore vision when corneal graft is a doomed failure. Although a number of KPros have been proposed, only two devices, Boston type-1 KPro and osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the latter is semi-biological in constitution. These two KPros have different surgical techniques and indications. Keratoprosthetic surgery is complex and should only be undertaken in specialized centers, where expertise, multidisciplinary teams, and resources are available. In this article, we briefly discuss some of the prominent historical KPros and contemporary devices. PMID:25945031

An experimental study of BIGH3 gene mutations in the patients with corneal dystrophies

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Jin Tao; Zou Liuhe; Yang Ling

2004-01-01

Objective: To evaluate BIGH3 gene mutations in Chinese patents with corneal dystrophies. Methods: 2ml peripheral venous blood was collected from 15 patients with granular corneal dystrophies and 5 normal subjects. Leucocytes DNA was extracted with standard method. With two pairs of oligonucleotide primers, exon 4 and exon 12 of the BIGH3 gene were amplified using the polymerase chain reaction. Amplified DNA fragments were purified and sequenced directly. Results: Mutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. 12 patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. 3 patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene. Conclusion: R124H and R555W mutations in BIGH3 gene were also found in the Chinese patients with Avellino and granular corneal dystrophies. In China, Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulted by BIGH3 gene mutions. Condon 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies. Molecular genetic analysis may be repuired for proper diagnosis and subclassification of corneal dystrophies. (authors)

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

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Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

2011-01-01

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

Corneal Endothelial Safety of Intracameral Preservative-free 1% Xylocaine

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Shah Alpesh

2004-01-01

Full Text Available Purpose : To evaluate the effect of intracameral preservative-free 1% xylocaine on the corneal endothelium as an adjuvant to topical anaesthesia during phacoemulsification and Acrysof foldable IOL implantation. Material & Methods: This is a prospective, controlled, randomised, double-masked study. 106 patients with soft to moderately dense (Grade 1-3 senile cataract and corneal endothelial cell density of >1500/mm2 were randomised to the xylocaine group (n=53 and control group(n=53. Central endothelial specular microscopy and ultrasound corneal pachymetry were performed preoperatively. On the first postoperative day the eyes were evaluated for corneal oedema and Descemet′s folds. Ultrasound corneal pachymetry was performed at 1, 3 and 12 months. Specular microscopy was performed at 3 and 12 months. Cell loss was expressed as a percentage of preoperative cell density. Six patients could not complete one year follow-up. Chi-square and paired t test (2 tail statistical tests were applied for analysis. Results: Four (7.54% patients in the xylocaine group and 5 (9.43% in the control group had a few Descemet′s folds associated with mild central stromal oedema. Corneal thickness increased from 549.3µ ± 37.2µ to 555.5µ ± 36.5µ in the xylocaine group and from 553.1µ ± 36.2µ to 559.3µ ± 40.5µ in the control group at the one-month postoperative visit. Thickness returned to the preoperative level in xylocaine group 549.6µ ± 34.5µ and control group 554.7µ ± 41.1µ at three months. (P=0.484 The percentage of cell loss was 4.47 ± 2.53% in the xylocaine group and 4.49 ± 3.09 % in the control group at one year. (P=0.97 Conclusion: Intracameral preservative-free 1% xylocaine does not appear to affect corneal endothelium adversely during phacoemulsification.

Validation of Na,K-ATPase pump function of corneal endothelial cells for corneal regenerative medicine.

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Hatou, Shin; Higa, Kazunari; Inagaki, Emi; Yoshida, Satoru; Kimura, Erika; Hayashi, Ryuhei; Tsujikawa, Motokazu; Tsubota, Kazuo; Nishida, Kohji; Shimmura, Shigeto

2013-12-01

Tissue-engineering approaches to cultivate corneal endothelial cells (CECs) or induce CECs from stem cells are under investigation for the treatment of endothelial dysfunction. Before clinical application, a validation method to determine the quality of these cells is required. In this study, we quantified the endothelial pump function required for maintaining the corneal thickness using rabbit CECs (RCECs) and a human CEC line (B4G12). The potential difference of RCECs cultured on a permeable polyester membrane (Snapwell), B4G12 cells on Snapwell, or B4G12 cells on a collagen membrane (CM6) was measured by an Ussing chamber system, and the effect of different concentrations of ouabain (Na,K-ATPase specific inhibitor) was obtained. A mathematical equation derived from the concentration curve revealed that 2 mM ouabain decreases pump function of RCECs to 1.0 mV, and 0.6 mM ouabain decreases pump function of B4G12 on CM6 to 1.0 mV. Ouabain injection into the anterior chamber of rabbit eyes at a concentration of pump function >1.0 mV is required to maintain the corneal thickness. These results can be used for standardization of CEC pump function and validation of tissue-engineered CEC sheets for clinical use.

An inducible mouse model of late onset Tay-Sachs disease.

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Jeyakumar, Mylvaganam; Smith, David; Eliott-Smith, Elena; Cortina-Borja, Mario; Reinkensmeier, Gabriele; Butters, Terry D; Lemm, Thorsten; Sandhoff, Konrad; Perry, V Hugh; Dwek, Raymond A; Platt, Frances M

2002-08-01

Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-/-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-/-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that approximately 65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P disease at an earlier age (n = 21, P Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway.

Ultrastructural study of Rift Valley fever virus in the mouse model

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Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E. [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States); Smith, Darci R., E-mail: darci.smith1@us.army.mil [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States)

2012-09-15

Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.

Ultrastructural study of Rift Valley fever virus in the mouse model

International Nuclear Information System (INIS)

Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E.; Smith, Darci R.

2012-01-01

Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV–host interactions and further characterize the mouse model of RVF.

Effects of edible bird's nest (EBN on cultured rabbit corneal keratocytes

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Hun Lee

2011-10-01

Full Text Available Abstract Background There has been no effective treatment or agent that is available for corneal injury in promoting corneal wound healing. Previous studies on edible bird's nest extract (EBN had reported the presence of hormone-like substance; avian epidermal growth factor that could stimulate cell division and enhance regeneration. This study aimed to investigate the effects of EBN on corneal keratocytes proliferative capacity and phenotypical changes. Methods Corneal keratocytes from six New Zealand White Rabbits were isolated and cultured until Passage 1. The proliferative effects of EBN on corneal keratocytes were determined by MTT assay in serum-containing medium (FDS and serum-free medium (FD. Keratocytes phenotypical changes were morphologically assessed and gene expression of aldehyde dehydrogenase (ALDH, collagen type 1 and lumican were determined through RT-PCR. Results The highest cell proliferation was observed when both media were supplemented with 0.05% and 0.1% EBN. Cell proliferation was also consistently higher in FDS compared to FD. Both phase contrast micrographs and gene expression analysis confirmed the corneal keratocytes retained their phenotypes with the addition of EBN. Conclusions These results suggested that low concentration of EBN could synergistically induce cell proliferation, especially in serum-containing medium. This could be a novel breakthrough as both cell proliferation and functional maintenance are important during corneal wound healing. The in vitro test is considered as a crucial first step for nutri-pharmaceutical formation of EBN-based eye drops before in vivo application.

Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

International Nuclear Information System (INIS)

Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

1983-01-01

Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [ 3 H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude

Active Transforming Growth Factor-beta2 in the Aqueous Humor of Posterior Polymorphous Corneal Dystrophy Patients

Czech Academy of Sciences Publication Activity Database

Stádníková, A.; Ďuďáková, L.; Skalická, P.; Valenta, Zdeněk; Filipec, M.; Jirsová, K.

2017-01-01

Roč. 12, č. 4 (2017), č. článku e0175509. E-ISSN 1932-6203 Grant - others:GA ČR(CZ) GA17-12355S; GA MŠk(CZ) 7F14156 Institutional support: RVO:67985807 Keywords : transforming growth factor-beta2 * posterior polymorphous corneal dystrophy * corneal endothelial cells * general linear mixed-effect modelling * restricted maximum likelihood estimation Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Statistics and probability Impact factor: 2.806, year: 2016

Engineering a new mouse model for vitiligo.

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Manga, Prashiela; Orlow, Seth J

2012-07-01

Although the precise mechanisms that trigger vitiligo remain elusive, autoimmune responses mediate its progression. The development of therapies has been impeded by a paucity of animal models, since mice lack interfollicular melanocytes, the primary targets in vitiligo. In this issue, Harris et al. describe a mouse model in which interfollicular melanocytes are retained by Kit ligand overexpression and an immune response is initiated by transplanting melanocyte-targeting CD8+ T cells.

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

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Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

2017-10-01

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

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Lois Choy

2016-09-01

Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

Comparison of stromal corneal nerves between normal and keratoconus patients using confocal microscopy.

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Ramírez Fernández, M; Hernández Quintela, E; Naranjo Tackman, R

2014-08-01

To evaluate the differences in stromal corneal nerves between normal patients and keratoconus patients. A total of 140 eyes of 70 normal patients (group A) and 122 eyes of 87 keratoconus patients (group B) were examined with the confocal microscope, with a central scan of the total corneal thickness being taken. The morphology and thickness of the corneal stromal nerves were evaluated by using the Navis v. 3.5.0. software. Nerve thickness was obtained from the mean between the widest and the narrowest portions of each stromal nerve. Corneal stromal nerves were observed as irregular linear hyper-reflective structures with wide and narrow portions in all cases. Mean corneal stromal nerves thickness in group A was 5.7±1.7 (range from 3.3 to 10.4 μ), mean corneal stromal nerves thickness in group B was 7.2±1.9 (range from 3.5 to 12.0 μ). There was a statistical significant difference (P<.05) in stromal corneal nerves thickness between group A and group B. Stromal corneal nerves morphology was similar in both groups, but stromal nerves were thicker in keratoconus patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

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Stefan Kurtenbach

Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

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Kathryn L McCabe

Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1 and Na+/K+ATPaseα1 (ATPA1 on the apical surface in monolayer culture, and produced the key proteins of Descemet's membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2. Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis.hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium.

Central Corneal Thickness And Its Relationship To Intra-ocular And Epidemiological Determinants

International Nuclear Information System (INIS)

Tayyab, A.; Masrur, A.

2016-01-01

Objective: To measure central corneal thickness in Pakistani population and determine its relationship to intra-ocular pressure, age, gender and ethnicity. Study Design: Cross-sectional observation study. Place and Duration of Study: Pakistan Institute of Medical Sciences, Islamabad, Pakistan, between December 2013 and February 2015. Methodology: The right eyes of 1000 cases (496 males and 504 females) were recruited for this study. Inclusion criteria were Pashtun or Punjabi ethnicity, intra-ocular pressure < 22 mmHg, gonioscopically open angles, cup-disk-ratio < 0.5, and age matched normal visual fields. Cases with prior ocular surgery, contact lens use, corneal pathologies, myopia or hypermetropia > ±3.0 diopters, astigmatism of > ±1.0 diopters were excluded. Central corneal thickness was measured using a TopCon non-contact specular microscope. Intra-ocular pressure was measured using Goldmann applanation tonometer. Frequency distribution, test of significance, and regression analysis was carried out using Statistical Package for Social Sciences version 20.0. Result: Mean age was 47.31 ±11.78 years. Ethnic composition was 51.6 percentage (n=516) Pashtun and 48.4 percentage (n=484) Punjabi. The mean central corneal thickness was 503.96 (±12.47) meu m, while the mean intra-ocular pressure was 15.61 (±2.68) mmHg. Regression analysis showed a significant association between central corneal thickness and intra-ocular pressure (p=0.00) and age (p=0.00). A ±100 μ change in central corneal thickness was associated with change in IOP of ±3.30 mmHg, whereas central corneal thickness decreased by 0.12 meu m per year. No significant association could be established between central corneal thickness and ethnicity (p=0.19). Conclusion: Central corneal thickness of the studied races was comparable to non-Caucasians which affects intra-ocular pressure measurements, and decreases with increasing age. No relationship was observed between central corneal thickness and

The Influence of Lamellar Orientation on Corneal Material Behavior: Biomechanical and Structural Changes in an Avian Corneal Disorder

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Elsheikh, Ahmed; Kassem, Wael; Kamma-Lorger, Christina S.; Hocking, Paul M.; White, Nick; Inglehearn, Chris F.; Ali, Manir; Meek, Keith M.

2011-01-01

Purpose. Retinopathy, globe enlarged (RGE) is an inherited genetic disease of chickens with a corneal phenotype characterized by loss of tissue curvature and changes in peripheral collagen fibril alignment. This study aimed to characterize the material behavior of normal and RGE chicken corneas under inflation and compare this with new spatial- and depth-resolved microstructural information to investigate how stromal fibril architecture determines corneal behavior under intraocular pressure (IOP). Methods. Six RGE chicken corneas and six age-matched normal controls were tested using trephinate inflation and their stress-strain behavior determined as a function of posterior pressure. Second harmonic generation mulitphoton microscopy was used to compare the in-plane appearance and degree of through-plane interlacing of collagen lamellae between normal and mutant corneas. Results. RGE corneas displayed a 30–130% increase in material stiffness [Etangent(RGE) = 0.94 ± 0.18 MPa to 3.09 ± 0.66 MPa; Etangent(normals) = 0.72 ± 0.13 MPa to 1.34 ± 0.35 MPa] (P ≤ 0.05). The normal in-plane disposition of anterior collagen in the peripheral cornea was altered in RGE but through-plane lamellar interlacing was unaffected. Conclusions. This article demonstrates changes in corneal material behavior in RGE that are qualitatively consistent with microstructural collagen alterations identified both herein and previously. This study indicates that, in general, changes in stromal fibril orientation may significantly affect corneal material behavior and thereby its response to IOP. PMID:21051696

Validation of Catquest-9SF-A Visual Disability Instrument to Evaluate Patient Function After Corneal Transplantation.

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Claesson, Margareta; Armitage, W John; Byström, Berit; Montan, Per; Samolov, Branka; Stenvi, Ulf; Lundström, Mats

2017-09-01

Catquest-9SF is a 9-item visual disability questionnaire developed for evaluating patient-reported outcome measures after cataract surgery. The aim of this study was to use Rasch analysis to determine the responsiveness of Catquest-9SF for corneal transplant patients. Patients who underwent corneal transplantation primarily to improve vision were included. One group (n = 199) completed the Catquest-9SF questionnaire before corneal transplantation and a second independent group (n = 199) completed the questionnaire 2 years after surgery. All patients were recorded in the Swedish Cornea Registry, which provided clinical and demographic data for the study. Winsteps software v.3.91.0 (Winsteps.com, Beaverton, OR) was used to assess the fit of the Catquest-9SF data to the Rasch model. Rasch analysis showed that Catquest-9SF applied to corneal transplant patients was unidimensional (infit range, 0.73-1.32; outfit range, 0.81-1.35), and therefore, measured a single underlying construct (visual disability). The Rasch model explained 68.5% of raw variance. The response categories of the 9-item questionnaire were ordered, and the category thresholds were well defined. Item difficulty matched the level of patients' ability (0.36 logit difference between the means). Precision in terms of person separation (3.09) and person reliability (0.91) was good. Differential item functioning was notable for only 1 item (satisfaction with vision), which had a differential item functioning contrast of 1.08 logit. Rasch analysis showed that Catquest-9SF is a valid instrument for measuring visual disability in patients who have undergone corneal transplantation primarily to improve vision.

Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

NARCIS (Netherlands)

Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.

Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35:

Healing of corneal epithelial wounds in marine and freshwater fish.

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Ubels, J L; Edelhauser, H F

The corneal epithelium of a fish is in direct contact with the aquatic environment and is a barrier to movement of ions and water into and through the cornea. This tissue layer is thus important in maintenance of corneal transparency. When the epithelium is wounded, its protective function is lost and corneal transparency remains compromised until the epithelial barrier is re-established. This study was undertaken to investigate the healing response of the fish cornea to epithelial abrasion. Wounds were stained with fluorescein and photographed during healing. Wound areas were measured by planimetry. The cornea of the sculpin, a marine teleost, becomes edematous after wounding and heals at 2.54 to 3.42 mm2/hr. Nonswelling corneas of the elasmobranchs--dogfish shark and skate--heal at 1.29 mm2/hr, respectively. The wounded eye of the rainbow trout, a freshwater teleost, is stressed by the low osmolality of the environment. Severe corneal edema and cataracts develop following epithelial wounding, and the cornea heals at 0.64 mm2/hr. Although the healing rates in teleosts differ from those in mammals, histology shows that the corneal healing mechanism is essentially the same in fish and mammals.

Fusarium dimerum Species Complex (Fusarium penzigii) Keratitis After Corneal Trauma.

Science.gov (United States)

do Carmo, Anália; Costa, Esmeralda; Marques, Marco; Quadrado, Maria João; Tomé, Rui

2016-12-01

We report a case of a keratitis associated with a Fusarium penzigii-a Fusarium dimerum species complex (FDSC)-in a 81-year-old woman after a corneal trauma with a tree branch. At patient admittance, slit lamp biomicroscopy revealed an exuberant chemosis, an inferior corneal ulcer with an associated inflammatory infiltrate, a central corneal abscess, bullous keratopathy and posterior synechiae. Corneal scrapes were obtained for identification of bacteria and fungi, and the patient started antibiotic treatment on empirical basis. Few days later, the situation worsened with the development of hypopyon. By that time, Fusarium was identified in cultures obtained from corneal scrapes and the patient started topical amphotericin B 0.15 %. Upon the morphological identification of the Fusarium as a FDSC, and since there was no clinical improvement, the treatment with amphotericin B was suspended and the patient started voriconazole 10 mg/ml, eye drops, hourly and voriconazole 200 mg iv, every 12 h for 1 month. The hypopyon resolved and the inflammatory infiltrate improved, but the abscess persisted at the last follow-up visit. The molecular identification revealed that the FDSC was a F. penzigii.

Nonspecific airway reactivity in a mouse model of asthma

Energy Technology Data Exchange (ETDEWEB)

Collie, D.D.; Wilder, J.A.; Bice, D.E.

1995-12-01

Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

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Felicia Leccia

2016-07-01

Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

Spallanzani's mouse: a model of restoration and regeneration.

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