Sample records for affecting retinal vascular

  1. Diabetes and Retinal Vascular Dysfunction

    Eui Seok Shin


    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  2. The Electroretinogram in Patients with Retinal Vascular Occlusion

    Shizhou Huang; Lezheng Wu; Taiqing Luo; De-Zheng Wu; Futian Jiang; Guangwei Luo; Juanmei Ma


    Purpose: to measure and analyze the electroretinogram (ERG) in patients with retinal vascular occlusion. Method: fifty-eight cases (59 eyes) of retinal vascular occlusion and the fellow eyes of 47 cases were tested with Ganzfeld ERG. The scotopic and photopic ERG, and oscillatory potentials were tested according to the ERG standard of ISCEV. Results: The abnormal rates of Ops and b wave were higher in retinal vascular occlusion. The abnormal ERG appeared mostly in CRVO among four types of retinal vascular occlusion. The comparisons of some amplitudes and latencies between the fellow eyes and the affected eyes showed statistically significant difference. Conclusion: The oscillatory potentials and b waves have important roles in evaluating the retinal function of patients with retinal vascular occlusions. There are some clinical significance for comparing ERG between the affected eye and the fellow eye. Eye Science 2001; 17: 50 ~ 53.

  3. Hypoxia-inducible factor and vascular endothelial growth factor in the neuroretina and retinal blood vessels after retinal ischemia

    Håkansson, Gisela; Gesslein, Bodil; Gustafsson, Lotta;


    Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor...... (VEGF) in retinal ischemia. Retinal ischemia was induced in porcine eyes by applying an intraocular pressure, followed by 12 h of reperfusion. HIF-1α mRNA expression was not affected by ischemia, while immunofluorescence staining was higher after ischemia in the neuroretina. HIF-1β immunoreactivity and...

  4. Retinal vascular oximetry during ranibizumab treatment of central retinal vein occlusion

    Traustason, Sindri; la Cour, Morten; Larsen, Michael


    PURPOSE: To investigate the effect of intravitreal injections of the vascular endothelial growth factor inhibitor ranibizumab on retinal oxygenation in patients with central retinal vein occlusion (CRVO). METHODS: Retinal oxygen saturation in patients with CRVO was analysed using the Oxymap Retin...

  5. Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

    Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.


    Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

  6. Retinal vascular calibres are significantly associated with cardiovascular risk factors

    von Hanno, T.; Bertelsen, G.; Sjølie, Anne K.;


    . Association between retinal vessel calibre and the cardiovascular risk factors was assessed by multivariable linear and logistic regression analyses. Results: Retinal arteriolar calibre was independently associated with age, blood pressure, HbA1c and smoking in women and men, and with HDL cholesterol in men......Purpose: To describe the association between retinal vascular calibres and cardiovascular risk factors. Methods: Population-based cross-sectional study including 6353 participants of the TromsO Eye Study in Norway aged 38-87years. Retinal arteriolar calibre (central retinal artery equivalent) and...... retinal venular calibre (central retinal vein equivalent) were measured computer-assisted on retinal photographs. Data on blood pressure, body mass index (BMI), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, glycosylated haemoglobin (HbA1c) and smoking were collected...

  7. Vascular endothelial growth factor blocking agents in retinal vein occlusion

    Chris Canning


    Full Text Available This paper summarises the current status of the use of vascular endothelial growth factor (VEGF blocking agents in retinal vein occlusion. There have been no randomised controlled trials comparing this treatment with the current standard treatment (largely laser so the lower grade evidence of single treatment case series and anecdotal reports are discussed. VEGF blockers are good at reducing macular oedema in the short term, do improve visual acuity in many cases, and do not seem to adversely affect the long term revascularisation that is necessary to overcome the vein occlusion. VEGF blocking agents are not used in isolation in this condition - they will remain an adjunct to systemic and other local treatments. The literature was reviewed in online searches of Embase and Ovid and the papers quoted are a representative sample of a larger body of publications.

  8. The Feasibility of Central Retinal Artery Doppler Ultrasonography in Patients with Sudden Visual Disturbance that's Caused by Retinal Vascular Occlusion

    We evaluated the usefulness of central retinal artery Doppler ultrasonography for assessing the patients with sudden visual disturbance that's caused by retinal vascular occlusion. The blood flow velocity and the resistive and pulsatile indexes were measured at the central retinal arteries of 65 patients with sudden visual disturbance. For all the subjects, the patient's affected eye was compared with the non-affected eye. We investigated the efficacy of the Doppler ultrasonography parameters to predict a significant visual loss on the Snellen test (<20/400). A significantly lower central retinal arterial flow velocity was measured in the affected eye as compared with the unaffected normal eye for all the subjects (p < 0.05). The ROC curves showed that the mean velocity was the best parameter to predict significant visual loss (p < 0.05). If a mean velocity of 4.3 cm/sec was chosen as the cutoff value to predict significant visual loss, then the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 89%, 95%, 95%, 88% and 92%, respectively (estimated area = 0.958, p-value <0.01). Central retinal artery Doppler ultrasonography was helpful for predicting significant visual loss in patients who complain of sudden visual disturbance. In addition to the other ophthalmologic diagnostic modalities, Doppler ultrasonography may be a feasible modality to depict impending further visual loss of an ischemic origin

  9. Familial correlation of retinal vascular caliber in Singapore Chinese

    L.-J. Li (Ling-Jun); J. Liao (Jie); Q. Fan (Qiao); C.Y.-L. Cheung (Carol Yim-Lui); M.A. Ikram (Arfan); C-Y. Cheng (Ching-Yu); S-M. Saw (Seang-Mei); T.Y. Wong (Tien)


    textabstractPurpose. Our study aimed to explore the heritability of retinal vascular caliber among Singapore Chinese families. Methods. In the Strabismus, Amblyopia, and Refractive Error Study in Singaporean Chinese Preschoolers (STARS) family study conducted from 2008 to 2010, a total of 727 partic

  10. Effect of ocular shape and vascular geometry on retinal hemodynamics: a computational model.

    Dziubek, Andrea; Guidoboni, Giovanna; Harris, Alon; Hirani, Anil N; Rusjan, Edmond; Thistleton, William


    A computational model for retinal hemodynamics accounting for ocular curvature is presented. The model combines (i) a hierarchical Darcy model for the flow through small arterioles, capillaries and small venules in the retinal tissue, where blood vessels of different size are comprised in different hierarchical levels of a porous medium; and (ii) a one-dimensional network model for the blood flow through retinal arterioles and venules of larger size. The non-planar ocular shape is included by (i) defining the hierarchical Darcy flow model on a two-dimensional curved surface embedded in the three-dimensional space; and (ii) mapping the simplified one-dimensional network model onto the curved surface. The model is solved numerically using a finite element method in which spatial domain and hierarchical levels are discretized separately. For the finite element method, we use an exterior calculus-based implementation which permits an easier treatment of non-planar domains. Numerical solutions are verified against suitably constructed analytical solutions. Numerical experiments are performed to investigate how retinal hemodynamics is influenced by the ocular shape (sphere, oblate spheroid, prolate spheroid and barrel are compared) and vascular architecture (four vascular arcs and a branching vascular tree are compared). The model predictions show that changes in ocular shape induce non-uniform alterations of blood pressure and velocity in the retina. In particular, we found that (i) the temporal region is affected the least by changes in ocular shape, and (ii) the barrel shape departs the most from the hemispherical reference geometry in terms of associated pressure and velocity distributions in the retinal microvasculature. These results support the clinical hypothesis that alterations in ocular shape, such as those occurring in myopic eyes, might be associated with pathological alterations in retinal hemodynamics. PMID:26445874

  11. Hemoglobin is associated with retinal vascular fractals in type 1 diabetes patients

    Nybo, Mads; Hodgson, Lauren A B; Kawasaki, Ryo;


    PURPOSE: Retinal vascular fractal dimension, a measure of the density of the retinal vasculature, has been suggested as a marker of systemic microvascular disorders in diabetes. As hemoglobin concentration is tightly related to vascular physiology and hypoxia, the hypothesis was that hemoglobin...... concentration would be associated with retinal vascular fractals in a relevant population. METHODS: In a cross-sectional study of 204 long-term type 1 diabetes patients from a population-based cohort, retinal digital photos were captured and graded for fractal dimension (Df) by International Retinal Imaging...... Software - Fractal (IRIS-Fractal). Df was calculated from a disc-centered retinal photo from the right eye. Hemoglobin concentrations were measured using routine equipment. RESULTS: Of 175 patients with gradable images, median age was 57.7 years and median duration of diabetes was 42 years. Median retinal...

  12. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee


    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. PMID:27462154

  13. Oral contraceptive pills: A risk factor for retinal vascular occlusion in in-vitro fertilization patients

    Rohina S Aggarwal; Mishra, Vineet V; Somesh V Aggarwal


    Retinal vascular occlusion is the most common cause of retinopathy leading to severe visual loss in all age groups. Central retinal vein occlusion (CRVO) is usually seen in older age group and is often associated with systemic vascular diseases. Although the exact cause and effect relationship has not been proven, central retinal vein occlusion has been associated with various systemic pathological conditions, hence a direct review of systems toward the various systemic and local factors pred...

  14. A Method for Visualization of Fine Retinal Vascular Pulsation Using Nonmydriatic Fundus Camera Synchronized with Electrocardiogram

    Dinesh Kant Kumar; Behzad Aliahmad; Hao Hao; Mohd Zulfaezal Che Azemin; Ryo Kawasaki


    Pulsatile changes in retinal vascular geometry over the cardiac cycle have clinical implication for diagnosis of ocular and systemic vascular diseases. In this study, we report a Vesselness Mapping of Retinal Image Sequence (VMRS) methodology to visualize the vessel pulsation and quantify the pulsatile motions in the cardiac cycle. Retinal images were recorded in an image sequence corresponding to 8 segments of the cardiac cycle using a nonmydriatic fundus camera (Canon CR45, Canon Inc., Japa...

  15. Clinical pathology and retinal vascular structure in the Bardet-Biedl syndrome.

    Bek, T; Rosenberg, T


    A comparative study of clinical pathology and retinal vascular structure is described as studied by vascular casting in an eye of a patient with the Bardet-Biedl syndrome. At the time of examination the eye had been almost blind for at least 4 years. The histopathological examination showed a largely uniform loss of the outer retinal layers. The gross pathological examination of the cast ocular fundus showed three distinct zones, an inner zone inside the temporal vascular arcades where retina...

  16. Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

    Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

  17. Quantitative Proteomics Reveals β2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability.

    Jo, Dong Hyun; Bae, Jingi; Chae, Sehyun; Kim, Jin Hyoung; Han, Jong-Hee; Hwang, Daehee; Lee, Sang-Won; Kim, Jeong Hun


    Retinal vascular hyperpermeability causes macular edema, leading to visual deterioration in retinal diseases such as diabetic retinopathy and retinal vascular occlusion. Dysregulation of junction integrity between endothelial cells by vascular endothelial growth factor (VEGF) was shown to cause retinal vascular hyperpermeability. Accordingly, anti-VEGF agents have been used to treat retinal vascular hyperpermeability. However, they can confer potential toxicity through their deleterious effects on maintenance and survival of neuronal and endothelial cells in the retina. Thus, it is important to identify novel therapeutic targets for retinal vascular hyperpermeability other than VEGF. Here, we prepared murine retinas showing VEGF-induced vascular leakage from superficial retinal vascular plexus and prevention of VEGF-induced leakage by anti-VEGF antibody treatment. We then performed comprehensive proteome profiling of these samples and identified retinal proteins for which abundances were differentially expressed by VEGF, but such alterations were inhibited by anti-VEGF antibody. Functional enrichment and network analyses of these proteins revealed the β2 integrin pathway, which can prevent dysregulation of junction integrity between endothelial cells through cytoskeletal rearrangement, as a potential therapeutic target for retinal vascular hyperpermeability. Finally, we experimentally demonstrated that inhibition of the β2 integrin pathway salvaged VEGF-induced retinal vascular hyperpermeability, supporting its validity as an alternative therapeutic target to anti-VEGF agents. PMID:26969716

  18. Correlation between penile cavernosal artery blood flow and retinal vascular findings in arteriogenic erectile dysfunction

    Ahmed M Emarah


    Full Text Available Ahmed M Emarah1, Shawky M El-Haggar2, Ihab A Osman2, Abdel Wahab S Khafagy21Departments of Ophthalmology, 2Andrology and Sexology, Cairo University Hospital, EgyptObjectives: Arteriogenic erectile dysfunction (ED is a target organ disease of atherosclerosis, and therefore might be a predictor of systemic atherosclerosis. Being systemic, it might be possible to evaluate the extent of atherosclerosis from retinal vascular findings. We investigated the possible correlation between penile cavernosal artery blood flow and retinal vascular findings in patients with arteriogenic ED.Patients and methods: Sixty patients with ED were divided according to the peak systolic velocity (PSV in their penile cavernosal arteries into two groups; Group A included 30 patients with PSV less than 25 cm/sec, and Group B included 30 patients with PSV more than 35 cm/sec. Blood flow in the penile cavernosal artery was measured with color Doppler ultrasonography. All patients were assessed by ocular fundus examination under amydriatic conditions to evaluate retinal vascular atherosclerotic changes using Hyman’s classification.Results: Evidence of retinal vascular atherosclerotic changes was found in 19 patients (63.3% in Group A and in 10 patients (33.3% in Group B.Conclusions: Our study confirms the possibility of predicting penile arterial vascular status in patients with ED from their retinal vascular findings by using amydriatic simple, practical funduscopy.Keywords: erectile dysfunction, atherosclerosis, retinal vascular atherosclerosis

  19. Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

    Junghyun Kim


    Full Text Available Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB breakage, we have used intravitreally methylglyoxal-(MGO- injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.

  20. Relationship between retinal vascular occlusions and incident cerebrovascular diseases: A systematic review and meta-analysis.

    Zhou, Yue; Zhu, Wengen; Wang, Changyun


    Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD.We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software.A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21-3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24-1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12-3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03-1.48; P = 0.04) were significantly associated with increased risk of CVD.Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  1. Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

    Vincent Daien

    Full Text Available PURPOSE: Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. PATIENTS AND METHODS: Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3 activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP and orosomucoid. RESULTS: In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003 whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001 and orosomucoid (p = 0.01. CONCLUSION: In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

  2. Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease.

    Li, Ling-Jun; Ikram, Mohammad Kamran; Wong, Tien Yin


    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non-invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low-fibre and high-sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre-clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood. PMID:26435039

  3. The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

    Huanling Yao; Tianshi Wang; Jiexin Deng; Ding Liu; Xiaofei Li; Jinbo Deng


    Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

  4. Influence of cataract surgery and blood pressure changes caused by sodium restriction on retinal vascular diameter

    Takatoshi Tano


    Full Text Available Takatoshi Tano1, Yoshimune Hiratsuka2, Koichi Ono1, Akira Murakami11Department of Ophthalmology, Juntendo University School of Medicine, Tokyo; 2National Institute of Public Health, Tokyo, JapanPurpose: To investigate the impact of cataract surgery and blood pressure changes induced by one week of sodium restriction on retinal vascular diameter.Methods: Fundus photographs of 200 patients were obtained before and one week after cataract surgery. For one week after admission, 100 patients received sodium restriction and 100 patients (ie, the control group did not receive sodium restriction. The diameter of the retinal vessels and blood pressure were compared between the sodium restriction group and the control group. The vascular diameter was measured using an objective computer-based method.Results: Neither group had a significant change in the diameter of the retinal vessels after cataract surgery. Although there was no significant change in retinal arterial and venular diameter in the sodium restriction group, one-week sodium restriction significantly reduced mean blood pressure. However, multiple linear regression analyses indicated that an increase in retinal arteriolar diameter was significantly associated with diabetes, hyperlipidemia, and alcohol intake.Conclusion: Cataract surgery and blood pressure reduction induced by one week of sodium restriction resulted in no significant change in retinal arteriolar diameter.Keywords: cataract surgery, hypertension, retinal blood vessel diameter, retinal fundus camera, sodium restriction.

  5. A rare and unusual retinal arterioarterial communication in a prepapillary vascular loop

    Makino, Shinji


    Fundus examination of a 40-year-old man presenting with blurred vision in his right eye revealed mild vitreous hemorrhage, a prepapillary vascular loop, and a peripapillary epiretinal membrane. Additionally, a superotemporal branch retinal artery communicated directly with an inferotemporal branch retinal artery in the temporal fovea at 2 locations. Fluorescein angiography confirmed an extremely rare arterioarterial communication. Two weeks later the vitreous hemorrhage and small intraretinal...

  6. Changes in the foveal microstructure after intravitreal bevacizumab application in patients with retinal vascular disease

    Feucht, Nikolaus


    Nikolaus Feucht, Etienne Michael Schönbach, Ines Lanzl, Konstantin Kotliar, Chris Patrick Lohmann, Mathias MaierDepartment of Ophthalmology, Technical University of Munich, Munich, GermanyPurpose: To investigate changes in the area of the foveal avascular zone (FAZ) in patients with retinal vascular disease.Patients and methods: This retrospective, consecutive study examined 53 eyes of 53 patients with macular edema due to branch retinal vein occlusion in 25 patients (47.2%) and nonp...

  7. Oral contraceptive pills: A risk factor for retinal vascular occlusion in in-vitro fertilization patients

    Rohina S Aggarwal


    Full Text Available Retinal vascular occlusion is the most common cause of retinopathy leading to severe visual loss in all age groups. Central retinal vein occlusion (CRVO is usually seen in older age group and is often associated with systemic vascular diseases. Although the exact cause and effect relationship has not been proven, central retinal vein occlusion has been associated with various systemic pathological conditions, hence a direct review of systems toward the various systemic and local factors predisposing the central retinal vein occlusion is advocated. We describe the development of central retinal venous occlusion with associated cystoid macular edema (CME in two healthy infertile women who were recruited for in vitro fertilization cycle for infertility. Predisposing risk factors associated with central retinal vein occlusion are obesity, sedentary life style, smoking, and some systemic diseases such as hyperlipidemia, hypertension, associated autoimmune disorders e.g., antiphospholipid antibody syndrome, lupus, diabetes mellitus, cardiovascular disorders, bleeding or clotting disorders, vasculitis, closed-head trauma, alcohol consumption, primary open-angle glaucoma or angle-closure glaucoma.In our patients, they were ruled out afterdoing allpertaining investigations. The cases were managed with further avoidance of oral contraceptives and intra-vitreal injections of Bevacizumab (Avastin, an anti-vascular endothelial growth factor (anti-VEGF drug and Triamcinolone acetonide (a long acting synthetic steroid. Hence, even if no systemic diseases are detected. Physical examinations are recommended periodically for young women on oral contraceptive pills.

  8. The unfolded protein response in retinal vascular diseases: implications and therapeutic potential beyond protein folding.

    Zhang, Sarah X; Ma, Jacey H; Bhatta, Maulasri; Fliesler, Steven J; Wang, Joshua J


    Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness. PMID:25529848

  9. Association of reduced Connexin 43 expression with retinal vascular lesions in human diabetic retinopathy.

    Tien, Thomas; Muto, Tetsuya; Zhang, Joyce; Sohn, Elliott H; Mullins, Robert F; Roy, Sayon


    Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years) and non-diabetic human eyes (aged 61-90 years) were analyzed in this study. Retinal protein samples and retinal capillary networks were assessed for Cx43 level by Western blot (WB) analysis and immunostaining. In parallel, retinal capillary networks were stained with hematoxylin and periodic acid Schiff to determine the extent of pericyte loss (PL) and acellular capillaries (AC) in these retinas. Cx43 protein expression was significantly reduced in the diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Additionally, a significant decrease in the number of Cx43 plaques per unit length of vessel was observed in the diabetic retinas compared to those of non-diabetic retinas (62 ± 10% of control; p diabetic retinas and Cx43 reduction is associated with increased vascular cell death. These findings suggest that diabetes decreases retinal Cx43 expression and that the development of PL and AC is associated with reduced Cx43 expression in human diabetic retinopathy. PMID:26738943

  10. Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury


    Background Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following retinal ischemia-reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of the blood-retinal barrier (BRB). Methods Male Sprague–Dawley rats were subjected to 45 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Rats were treated with Mino prior to and following IR. At 48 h after reperfusion, retinal gene expression, cellular inflammation, Evan’s blue dye leakage, tight junction protein organization, caspase-3 activation, and DNA fragmentation were measured. Cellular inflammation was quantified by flow-cytometric evaluation of retinal tissue using the myeloid marker CD11b and leukocyte common antigen CD45 to differentiate and quantify CD11b+/CD45low microglia, CD11b+/CD45hi myeloid leukocytes and CD11bneg/CD45hi lymphocytes. Major histocompatibility complex class II (MHCII) immunoreactivity was used to determine the inflammatory state of these cells. Results Mino treatment significantly inhibited IR-induced retinal vascular permeability and disruption of tight junction organization. Retinal IR injury significantly altered mRNA expression for 21 of 25 inflammation- and gliosis-related genes examined. Of these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2 (LCN2), serpin peptidase inhibitor clade A member 3 N (SERPINA3N), TNF receptor superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment significantly reduced retinal leukocyte numbers following IR and was particularly effective in decreasing the

  11. Retinal vascular changes in hypertensive patients in Ibadan, Sub-Saharan Africa

    Oluleye ST


    Full Text Available Sunday Tunji Oluleye,1 Bolutife Ayokunu Olusanya,1 Abiodun Moshood Adeoye2 1Department of Ophthalmology, 2Department of Medicine, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria Background: Earlier studies in Nigeria reported the rarity of retinal vascular changes in hypertensives. The aim of this study was to describe the various retinal vascular changes in the hypertensive patients of Nigeria.Patients and methods: Nine hundred and three hypertensive patients were studied. This study was approved by the ethical and research committee of the University of Ibadan and University College Hospital, Ibadan, Nigeria. Blood pressure and anthropometric measurements were measured. Cardiac echocardiography was performed on 156 patients. All patients had dilated fundoscopy and fundus photography using the Kowa portable fundus camera and an Apple iPhone with 20 D lens. Statistical analysis was done with Statistical Packages for the Social Sciences (Version 21.Results: The mean age of patients was 57 years with a male:female ratio of 1. No retinopathy was found in 556 (61.5% patients. In all, 175 (19.4% patients had features of hypertensive retinopathy. Retinal vascular occlusion was a significant finding in 121 patients (13.4%, of which branch retinal vein occlusion, 43 (4.7%, and central retinal vein occlusion, 30 (3.3%, were the most prominent ones in cases. Hemicentral retinal vein occlusion, 26 (2.9%, and central retinal artery occlusion, 17 (1.9%, were significant presentations. Other findings included nonarteritic anterior ischemic optic neuropathy in five (0.6% patients, hypertensive choroidopathy in seven (0.8% patients, and hemorrhagic choroidal detachment in five (0.6% patients. Left ventricular (LV geometry was abnormal in 85 (55.5% patients. Concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were observed in 43 (27.6%, 26 (17.2%, and 15 (9.7% patients, respectively. LV

  12. Arginase 2 deficiency prevents oxidative stress and limits hyperoxia-induced retinal vascular degeneration.

    Jutamas Suwanpradid

    Full Text Available BACKGROUND: Hyperoxia exposure of premature infants causes obliteration of the immature retinal microvessels, leading to a condition of proliferative vitreoretinal neovascularization termed retinopathy of prematurity (ROP. Previous work has demonstrated that the hyperoxia-induced vascular injury is mediated by dysfunction of endothelial nitric oxide synthase resulting in peroxynitrite formation. This study was undertaken to determine the involvement of the ureahydrolase enzyme arginase in this pathology. METHODS AND FINDINGS: Studies were performed using hyperoxia-treated bovine retinal endothelial cells (BRE and mice with oxygen-induced retinopathy (OIR as experimental models of ROP. Treatment with the specific arginase inhibitor 2(S-amino-6-boronohexanoic acid (ABH prevented hyperoxia-induced apoptosis of BRE cells and reduced vaso-obliteration in the OIR model. Furthermore, deletion of the arginase 2 gene protected against hyperoxia-induced vaso-obliteration, enhanced physiological vascular repair, and reduced retinal neovascularization in the OIR model. Additional deletion of one copy of arginase 1 did not improve the vascular pathology. Analyses of peroxynitrite by quantitation of its biomarker nitrotyrosine, superoxide by dihydroethidium imaging and NO formation by diaminofluoroscein imaging showed that the protective actions of arginase 2 deletion were associated with blockade of superoxide and peroxynitrite formation and normalization of NOS activity. CONCLUSIONS: Our data demonstrate the involvement of arginase activity and arginase 2 expression in hyperoxia-induced vascular injury. Arginase 2 deletion prevents hyperoxia-induced retinal vascular injury by preventing NOS uncoupling resulting in decreased reactive oxygen species formation and increased nitric oxide bioavailability.

  13. Differential Diagnosis of Retinal Vasculitis

    Abu El-Asrar, Ahmed M.; Herbort, Carl P.; Tabbara, Khalid F.


    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings. PMID:20404987

  14. Differential Diagnosis of Retinal Vasculitis

    Abu El-Asrar Ahmed; Herbort Carl; Tabbara Khalid


    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein a...

  15. Differential diagnosis of retinal vasculitis

    Abu El-Asrar Ahmed


    Full Text Available Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  16. PARP1 gene knock-out increases resistance to retinal degeneration without affecting retinal function.

    Ayse Sahaboglu

    Full Text Available Retinitis pigmentosa (RP is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt. Likewise, retinal function as assessed by electroretinography (ERG was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6, we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.


    Wiertz, Karin; De Visser, Lenneke; Rijkers, Ger; De Groot-Mijnes, Jolanda; Los, Leonie; Rothova, Aniki


    Purpose: To determine the intraocular and serum vascular endothelial growth factor (VEGF) levels in patients with acute retinal necrosis (ARN) and compare those with VEGF levels found in patients with ocular toxoplasmosis (OT). Methods: Paired intraocular fluid and serum samples of 17 patients with

  18. Automatic detection of vascular bifurcations in segmented retinal images using trainable COSFIRE filters

    Azzopardi, George; Petkov, Nicolai


    Background: The vascular tree observed in a retinal fundus image can provide clues for cardiovascular diseases. Its analysis requires the identification of vessel bifurcations and crossovers. Methods: We use a set of trainable keypoint detectors that we call Combination Of Shifted Filter REsponses o

  19. RNA interference inhibits expression of vascular endothelial growth factor (VEGF) in human retinal pigment epithelial cells

    CAI Chun-mei; SUN Bao-chen; LIU Xu-yang; WANG Jin-jin; LI Jun-fa; HAN Song; WANG Ning-li; LU Qing-jun


    @@ Choroidal neovascularization (CNV), a major cause of vision loss, is the result of the increased vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. It is important to inhibit the expression of VEGF protein in RPE cells.

  20. Assessing the Causality between Blood Pressure and Retinal Vascular Caliber through Mendelian Randomisation

    Li, Ling-Jun; Liao, Jiemin; Cheung, Carol Yim-Lui; Ikram, M. Kamran; Shyong, Tai E.; Wong, Tien-Yin; Cheng, Ching-Yu


    We aimed to determine the association between blood pressure (BP) and retinal vascular caliber changes that were free from confounders and reverse causation by using Mendelian randomisation. A total of 6528 participants from a multi-ethnic cohort (Chinese, Malays, and Indians) in Singapore were included in this study. Retinal arteriolar and venular caliber was measured by a semi-automated computer program. Genotyping was done using Illumina 610-quad chips. Meta-analysis of association between BP, and retinal arteriolar and venular caliber across three ethnic groups was performed both in conventional linear regression and Mendelian randomisation framework with a genetic risk score of BP as an instrumental variable. In multiple linear regression models, each 10 mm Hg increase in systolic BP, diastolic BP, and mean arterial BP (MAP) was associated with significant decreases in retinal arteriolar caliber of a 1.4, 3.0, and 2.6 μm, and significant decreases in retinal venular caliber of a 0.6, 0.7, and 0.9 μm, respectively. In a Mendelian randomisation model, only associations between DBP and MAP and retinal arteriolar narrowing remained yet its significance was greatly reduced. Our data showed weak evidence of a causal relationship between elevated BP and retinal arteriolar narrowing.

  1. Retinal vascular calibre and response to light exposure and serial imaging

    von Hanno, T.; Sjølie, Anne K.; Mathiesen, E. B.


    Purpose: To investigate whether retinal vessel calibre measurements on optical retinal photography are affected by light and dark exposure prior to photography and whether the vessel calibre changes during an imaging sequence of several images. Methods: Digital optical retinal photographs were...... obtained from 32 healthy adults in two separate image sequences of six images during 1 min; one sequence with 10 min of dark exposure and one with 10 min of light exposure prior to imaging. Retinal arteriolar and venular calibres were measured computer-assisted and summarized as central retinal artery and...... vein equivalents (CRAE and CRVE). Outcome measures were difference in calibres after prior light versus prior dark exposure and difference in calibre during each of the two imaging sequences. Results: CRVE was wider with prior light exposure (2.7%, p = 0.0001), comparing the first image in each image...

  2. Accelerated ischemic vascular retinopathy after intravitreally injected bevacizumab for central retinal vein occlusion in elderly patients

    Isola V


    Full Text Available Vincenzo Isola,1 Alfredo Pece,1,2 Claudio Massironi,1 Simone Reposi,1 Fabio Dimastrogiovanni11Department of Ophthalmology, Melegnano Hospital, 2Fondazione Retina 3000, Milano, ItalyBackground: Ischemic changes in the retinal circulation are an uncommon but severe adverse vascular reaction to intravitreal bevacizumab (Avastin®, Genentech, San Francisco, CA, USA/Roche, Basel, Switzerland for central retinal vein occlusion (CRVO. In the two cases reported here, ischemic changes in the retina vasculature following intravitreal bevacizumab for CRVO were observed with the aim of describing the clinical and angiographic features of these changes.Methods: Two elderly patients with recent-onset CRVO received one off-label intravitreal injection of bevacizumab 0.05 mL/1.25 mg.Results: In Case 1, the patient's pre-treatment visual acuity was 20/400. At 3 weeks post injection, the patient could count fingers at a distance of 1 ft (30 cm and fluorescein angiography showed reduction in intraretinal hemorrhages and areas of retinal non-perfusion. However, at 6 weeks these were markedly increased compared with those seen in the photograph taken 3 weeks after treatment. In Case 2, the patient's pre-treatment visual acuity was 20/200. At 1 month post injection, vision had decreased to 20/400 and fluorescein angiography showed severe macular ischemia with a remarkable capillary dropout throughout the macula.Conclusion: Ischemic retinal injury may be an uncommon but severe adverse vascular reaction to intravitreal bevacizumab for CRVO. Although progression of retinal ischemia in CRVO could be observed shortly after intravitreal bevacizumab, whether this is a drug- or procedure-related effect or part of the natural history of the condition remains uncertain.Keywords: Avastin, ischemia, macular infarction, intraretinal hemorrhage, retinal non-perfusion

  3. Estimating retinal vascular permeability using the adiabatic approximation to the tissue homogeneity model with fluorescein videoangiography

    Tichauer, Kenneth M.; Osswald, Christian R.; Dosmar, Emily; Guthrie, Micah J.; Hones, Logan; Sinha, Lagnojita; Xu, Xiaochun; Mieler, William F.; St. Lawrence, Keith; Kang-Mieler, Jennifer J.


    Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today's treatment standards. As a result, there is a push to develop new, "sub-clinical" methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.

  4. Arginase 2 Deficiency Prevents Oxidative Stress and Limits Hyperoxia-Induced Retinal Vascular Degeneration

    Suwanpradid, Jutamas; Rojas, Modesto; Behzadian, M. Ali; Caldwell, R. William; Caldwell, Ruth B.


    Background Hyperoxia exposure of premature infants causes obliteration of the immature retinal microvessels, leading to a condition of proliferative vitreoretinal neovascularization termed retinopathy of prematurity (ROP). Previous work has demonstrated that the hyperoxia-induced vascular injury is mediated by dysfunction of endothelial nitric oxide synthase resulting in peroxynitrite formation. This study was undertaken to determine the involvement of the ureahydrolase enzyme arginase in thi...

  5. Correlation between penile cavernosal artery blood flow and retinal vascular findings in arteriogenic erectile dysfunction

    Emarah, Ahmed


    Ahmed M Emarah1, Shawky M El-Haggar2, Ihab A Osman2, Abdel Wahab S Khafagy21Departments of Ophthalmology, 2Andrology and Sexology, Cairo University Hospital, EgyptObjectives: Arteriogenic erectile dysfunction (ED) is a target organ disease of atherosclerosis, and therefore might be a predictor of systemic atherosclerosis. Being systemic, it might be possible to evaluate the extent of atherosclerosis from retinal vascular findings. We investigated the possible correlation between penile cavern...

  6. βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

    Sinha, Debasish; Klise, Andrew; Sergeev, Yuri; Hose, Stacey; Bhutto, Imran A.; Hackler, Laszlo; Malpic-llanos, Tanya; Samtani, Sonia; Grebe, Rhonda; Goldberg, Morton F.; Hejtmancik, J. Fielding; Nath, Avindra; Zack, Donald J.; Fariss, Robert N.; McLeod, D. Scott; Sundin, Olof; Broman, Karl W.; Lutty, Gerard A.; Zigler, J. Samuel


    Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague–Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina. PMID:17931883

  7. Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo

    Joussen, Antonia M; Poulaki, Vassiliki; Qin, Wenying; Kirchhof, Bernd; Mitsiades, Nicholas; Wiegand, Stanley J; Rudge, John; George D. Yancopoulos; Adamis, Anthony P.


    Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxid...

  8. Comprehensive automatic assessment of retinal vascular abnormalities for computer-assisted retinopathy grading.

    Joshi, Vinayak; Agurto, Carla; VanNess, Richard; Nemeth, Sheila; Soliz, Peter; Barriga, Simon


    One of the most important signs of systemic disease that presents on the retina is vascular abnormalities such as in hypertensive retinopathy. Manual analysis of fundus images by human readers is qualitative and lacks in accuracy, consistency and repeatability. Present semi-automatic methods for vascular evaluation are reported to increase accuracy and reduce reader variability, but require extensive reader interaction; thus limiting the software-aided efficiency. Automation thus holds a twofold promise. First, decrease variability while increasing accuracy, and second, increasing the efficiency. In this paper we propose fully automated software as a second reader system for comprehensive assessment of retinal vasculature; which aids the readers in the quantitative characterization of vessel abnormalities in fundus images. This system provides the reader with objective measures of vascular morphology such as tortuosity, branching angles, as well as highlights of areas with abnormalities such as artery-venous nicking, copper and silver wiring, and retinal emboli; in order for the reader to make a final screening decision. To test the efficacy of our system, we evaluated the change in performance of a newly certified retinal reader when grading a set of 40 color fundus images with and without the assistance of the software. The results demonstrated an improvement in reader's performance with the software assistance, in terms of accuracy of detection of vessel abnormalities, determination of retinopathy, and reading time. This system enables the reader in making computer-assisted vasculature assessment with high accuracy and consistency, at a reduced reading time. PMID:25571442

  9. Retinal vascular fractal dimension, childhood IQ, and cognitive ability in old age: the Lothian Birth Cohort Study 1936.

    Adele M Taylor

    Full Text Available Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (Df as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability.Participants from the Lothian Birth Cohort 1936 Study (LBC1936 had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648. IQ scores were available from childhood. Retinal vascular Df was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular Df and general cognitive ability (g, processing speed, and memory.Only three out of 24 comparisons (two eyes × four Df parameters × three cognitive measures were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye.The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing.

  10. Changes in the foveal microstructure after intravitreal bevacizumab application in patients with retinal vascular disease

    Feucht N


    Full Text Available Nikolaus Feucht, Etienne Michael Schönbach, Ines Lanzl, Konstantin Kotliar, Chris Patrick Lohmann, Mathias MaierDepartment of Ophthalmology, Technical University of Munich, Munich, GermanyPurpose: To investigate changes in the area of the foveal avascular zone (FAZ in patients with retinal vascular disease.Patients and methods: This retrospective, consecutive study examined 53 eyes of 53 patients with macular edema due to branch retinal vein occlusion in 25 patients (47.2% and nonproliferative diabetic retinopathy in 28 patients (52.8%. The macular edema was treated with an intravitreal injection of 0.05 mL equal to 1.25 mg bevacizumab. Before and 6–8 weeks after the injection, best corrected visual acuity, slit lamp biomicroscopy of the anterior segment and fundus, optical coherence tomography, and fluorescein angiography were conducted. The FAZ was manually circumscribed on early-phase angiography images and the area of the FAZ was measured.Results: The preoperative overall mean FAZ area was 0.327 ± 0.126 mm2 (median 0.310 mm2. At the control consultation, the overall mean area was significantly larger (0.422 ± 0.259 mm2; median 0.380 mm2; P < 0.001. In the nonproliferative diabetic retinopathy subpopulation, the mean area was 0.361 ± 0.129 mm2 (median 0.330 mm2 before bevacizumab application and 0.434 mm2 at the follow-up visit (mean increase 0.071 mm2/19.7%. In the branch retinal vein occlusion group, the baseline FAZ area was 0.290 ± 0.115 mm2 and 0.407 ± 0.350 mm2 at follow-up (median 0.330 mm2; mean increase 0.117 mm2/40.3%. No cases of severe operation-associated complications were observed.Conclusion: The results confirm the safety of intravitreal bevacizumab injection in patients with macular edema due to nonproliferative diabetic retinopathy and branch retinal vein occlusion. The enlargement of the FAZ could be equivalent to an increase in retinal ischemia. These results may be transient; a potential vascular risk, however

  11. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  12. The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy

    C. Moran


    Full Text Available It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years and 181 without T2DM (mean age 72.9 years. T2DM was associated with lower gray matter volume (p=0.008. T2DM was associated with greater arteriolar diameter (p=0.03 and optimality ratio (p=0.04, but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p=0.03. The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy.

  13. Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia.

    Pfister, Frederick; Wang, Yumei; Schreiter, Kay; vom Hagen, Franziska; Altvater, Karin; Hoffmann, Sigrid; Deutsch, Urban; Hammes, Hans-Peter; Feng, Yuxi


    Our previous data suggested that angiopoietin-2 (Ang-2) is linked to pericyte loss, thereby playing an important role in diabetic retinopathy. In this study, we investigated the effect of retinal overexpression of human Ang-2 (mOpsinhAng2 mouse) on vascular morphology in non-diabetic and streptozotozin-induced diabetic animals. Pericyte (PC) coverage and acellular capillary (AC) formation were quantitated in retinal digest preparations after 3 and 6 months of diabetes duration. The degree of retinopathy in non-diabetic mOpsinhAng2 mice at 3 months (-21% PC, +49% AC) was comparable to age-matched diabetic wild type mice. Diabetic mOpsinhAng2 mice exhibited significantly worse vascular pathology than wild type counterparts at 6 months. Quantitative PCR revealed that human Ang-2 mRNA was highly overexpressed in retinas of transgenic mice. Our data demonstrate that overexpression of Ang-2 in the retina enhances vascular pathology, indicating that Ang-2 plays an essential role in diabetic vasoregression via destabilization of pericytes. PMID:19238311

  14. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)


    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

  15. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

    Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O2). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice

  16. Zebrafish (Danio rerio) embryo as a platform for the identification of novel angiogenesis inhibitors of retinal vascular diseases.

    Rezzola, Sara; Paganini, Giuseppe; Semeraro, Francesco; Presta, Marco; Tobia, Chiara


    Pathological angiogenesis of the retina is a main cause of blindness. Therapeutic approaches targeting vascular endothelial growth factor, a main angiogenesis inducer in retinal vascular diseases, show significant limitations. Thus, experimental models of retinal neovascularization remain crucial for investigating novel anti-angiogenic strategies and bringing them to patients. Recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryo may represent a novel target for the identification of angiogenesis inhibitors. This review highlights the use of zebrafish embryo as an innovative model system for the screening of anti-angiogenic molecules to be employed for the treatment of angiogenesis-dependent eye diseases. PMID:27085972

  17. MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells

    Tagami, Mizuki [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Kusuhara, Sentaro, E-mail: [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Imai, Hisanori [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Uemura, Akiyoshi [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Department of Vascular Biology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)


    Research highlights: {yields} Exogenous VEGF decreases MRP4 expression in a dose-dependent manner. {yields} MRP4 knockdown leads to enhanced cell migration. {yields} MRP4 knockdown suppresses caspase-3-mediated cell apoptosis. {yields} MRP4 knockdown produces cell assembly and cell aggregation. -- Abstract: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.

  18. Inter-Eye Agreement in Measurement of Retinal Vascular Fractal Dimension in Patients with Type 1 Diabetes Mellitus

    Pedersen, Knud B; Broe, Rebecca; Grauslund, Jakob


    PURPOSE: To investigate inter-eye agreement in retinal vascular fractal dimension (FD) in patients with type 1 diabetes. METHODS: In a cross-sectional study, both eyes were exained in 178 patients with type 1 diabetes. All vessels in a zone 0.5-2.0 disc diameters from the optic disc were traced a...

  19. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.

    Weinl, Christine; Wasylyk, Christine; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Beck, Susanne C; Riehle, Heidemarie; Stritt, Christine; Roux, Michel J; Seeliger, Mathias W; Wasylyk, Bohdan; Nordheim, Alfred


    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/-) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/-) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(-/-) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients. PMID:25203538

  20. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.

    Christine Weinl

    Full Text Available Serum Response Factor (SRF fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/- mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/- mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF in the affected eyes. However, in Elk3(-/- mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients.

  1. Fatp1 deficiency affects retinal light response and dark adaptation, and induces age-related alterations.

    Karim Chekroud

    Full Text Available FATP1 is involved in lipid transport into cells and in intracellular lipid metabolism. We showed previously that this protein interacts with and inhibits the limiting-step isomerase of the visual cycle RPE65. Here, we aimed to analyze the effect of Fatp1-deficiency in vivo on the visual cycle, structure and function, and on retinal aging. Among the Fatp family members, we observed that only Fatp1 and 4 are expressed in the control retina, in both the neuroretina and the retinal pigment epithelium. In the neuroretina, Fatp1 is mostly expressed in photoreceptors. In young adult Fatp1(-/- mice, Fatp4 expression was unchanged in retinal pigment epithelium and reduced two-fold in the neuroretina as compared to Fatp1(+/+ mice. The Fatp1(-/- mice had a preserved retinal structure but a decreased electroretinogram response to light. These mice also displayed a delayed recovery of the b-wave amplitude after bleaching, however, visual cycle speed was unchanged, and both retinal pigment epithelium and photoreceptors presented the same fatty acid pattern compared to controls. In 2 year-old Fatp1(-/- mice, transmission electron microscopy studies showed specific abnormalities in the retinas comprising choroid vascularization anomalies and thickening of the Bruch membrane with material deposits, and sometimes local disorganization of the photoreceptor outer segments. These anomalies lead us to speculate that the absence of FATP1 accelerates the aging process.

  2. The effect of voluntary fasting and dehydration on flicker-induced retinal vascular dilation in a healthy individual: a case report

    Heitmar Rebekka


    Full Text Available Abstract Introduction Dynamic retinal vessel analysis represents a well-established method for the assessment of vascular reactivity during both normal conditions and after various provocations. We present a case where the subject showed abnormal retinal vessel reactivity after fasting voluntarily for 20 hours. Case presentation A healthy, 21-year-old man who fasted voluntarily for 20 hours exhibited abnormal retinal vascular reactivity (dilation and constriction after flicker provocation as measured using the Dynamic Retinal Vessel Analyser (Imedos, Jena, Germany. Conclusion The abnormal vascular reactivity induced by fasting was significant; abnormal levels of important nutrients due to fasting and dehydration could play a role through altering the concentration of vasoactive substances such as nitric oxide. This hypothesis needs further investigation.

  3. Freezing adversely affects measurement of vascular endothelial growth factor levels in human aqueous samples

    Sankarathi Balaiya


    Full Text Available Sankarathi Balaiya Sandeep Grover Ravi K Murthy Kakarla V ChalamDepartment of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL, USAPurpose: Aqueous levels of vascular endothelial growth factor (VEGF can be a surrogate marker of intraocular VEGF activity and a measure of efficacy of anti-VEGF treatment in a variety of vasoproliferative retinal disorders, including diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusion. Measurement of the VEGF level may be adversely affected by premeasurement variables, such as freezing and delay, in sample analysis. We aim to evaluate the effect of storage and delayed measurement of human aqueous VEGF levels in these conditions.Methods: Aqueous samples collected from patients receiving intravitreal injection of bevacizumab for various retinal diseases were divided into two groups. In Group 1, the VEGF levels were analyzed on the same day; in Group 2, the VEGF levels were analyzed after 21 days of freezer storage (-80°C using immunobead assay. Statistical comparison using a paired t-test was performed between the two groups.Results: Thirty-one aqueous humor samples were collected, and the VEGF concentration for fresh samples was 7.8 ± 5.9 pg/mL (mean ± SD compared to 6.5 ± 6.0 pg/mL in frozen samples, resulting in a statistically significant difference (P = 0.03.Conclusions: Accurate measurement of the VEGF level is a vital component of clinical decision-making. Delayed analysis of VEGF levels in aqueous samples may result in significant sample degradation and lower levels of measured VEGF.Keywords: VEGF level, aqueous humor, immunobead assay, VEGF storage

  4. Other Retinal Diseases

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... affected by retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases. ...


    R. Franceschini


    Full Text Available Purpose. To present a case of retinal and choroidal vascular occlusion in conjunction with HELLP syndrome. Methods. A 35 years-old woman presented with HELLP syndrome underwent cesarean delivery for preeclampsia. After 2 months she had a decrease of vision in OD. She had performed an eye examination with FAG and ICG. results. The FAG shows at the posterior pole in the perifoveola temporal area different areas of hyperfluorescence. ICG reveals frameworks of hypoperfusion in perimacular areas, for the probable presence of ischemic foci. After about 5 mounths she presented an improvement in visual acuity and a complete resolution of Ophtalmoscopic findings. Conclusions. Ophtalmic complications are possible during this syndrome. This is the first description of a patient suffering a retinal and choroidal vascolar occlusion after HELLP syndrome, and we report the important of ICG for\tdiagnosis\tof choroidal ischemia.

  6. Retinal Vascular Fractals and Microvascular and Macrovascular Complications in Type 1 Diabetes

    Grauslund, Jakob; Green, Anders; Kawasaki, Ryo;


    with a semiautomatic computer-based program (International Retinal Imaging Software; National University of Singapore, Republic of Singapore; University of Sydney, Sydney, and University of Melbourne, Melbourne, Australia). D(f) of the retinal vasculature was measured within a predefined circular region of 3.5 optic...... in any materials discussed in this article....

  7. Summarising the retinal vascular calibres in healthy, diabetic and diabetic retinopathy eyes.

    Leontidis, Georgios; Al-Diri, Bashir; Hunter, Andrew


    Retinal vessel calibre has been found to be an important biomarker of several retinal diseases, including diabetic retinopathy (DR). Quantifying the retinal vessel calibres is an important step for estimating the central retinal artery and vein equivalents. In this study, an alternative method to the already established branching coefficient (BC) is proposed for summarising the vessel calibres in retinal junctions. This new method combines the mean diameter ratio with an alternative to Murray׳s cube law exponent, derived by the fractal dimension,experimentally, and the branch exponent of cerebral vessels, as has been suggested in previous studies with blood flow modelling. For the above calculations, retinal images from healthy, diabetic and DR subjects were used. In addition, the above method was compared with the BC and was also applied to the evaluation of arteriovenous ratio as a biomarker of progression from diabetes to DR in four consecutive years, i.e. three/two/one years before the onset of DR and the first year of DR. Moreover, the retinal arteries and veins around the optic nerve head were also evaluated. The new approach quantifies the vessels more accurately. The decrease in terms of the mean absolute percentage error was between 0.24% and 0.49%, extending at the same time the quantification beyond healthy subjects. PMID:27017067

  8. Retinal vascular fractal dimension as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

    Torp, Thomas Lee; Vergmann, Anna Stage; Peto, Tunde;


    Design of study: Six months prospective, interventional clinical study. Purpose: The retinal vascular fractal dimension (FD) is a non-invasive marker of retinal vascular geometry. The purpose of the study was to evaluate FD as a preoperative biomarker for disease activity 6 month after panretinal...... of diabetes were 52±14 years and 21±11 years, respectively, and 75% were male. HbA1c was 68 ±16 mmol/mol, and the mean blood pressure was 183/84 mmHg. Groups 1 and 2 did not differ according to the mean number of laser spots (1581 vs. 1573, p=0.84) or the total laser energy delivered (13.67 joule vs...... (group 1, n=18) or stabilized (group 2, n=22) disease. FD was measured at baseline and month 6 by a trained grader using the Fractal Analyzer (Singapore Institute Vessel Assessment-Fractal image analysis software, Singapore) and a standardized grading-protocol. Results: At baseline, mean age and duration...

  9. Serial evaluation of retinal vascular changes in infants treated with intravitreal bevacizumab for aggressive posterior retinopathy of prematurity in zone I.

    Padhi, T R; Das, T; Rath, S; Pradhan, L; Sutar, S; Panda, K G; Modi, R; Jalali, S


    PurposeTo evaluate the serial changes in retinal vasculature in infants treated with intravitreal bevacizumab (IVB) for aggressive posterior retinopathy of prematurity (APROP) in zone I.MethodsRetrospective analysis of serial changes in retinal vasculature after IVB in the seven eyes of four babies with APROP in zone I.ResultsThe initial regression, following IVB, was dramatic with reduction in vessel caliber and marked thinning and invisibility of the bridging shunts. Resurgent vascular development was very slow radially though there was continued abnormal vascular growth circumferentially. Common findings in all eyes were tangled vasculature and fine saw-toothed shunts. The variable findings were (1) new closely packed multilayered bridging shunts, long arching mature looking vessels, and finally a ridge at the periphery (n=3 eyes) at 52 weeks of postmenstrual age (PMA); (2) status quo at the stage of saw-toothed shunt and ridge in both eyes for a long time (n=2 eyes); and (3) multiple retinal hemorrhages within the vascularized retina and thick preretinal hemorrhage overlying the saw-toothed shunts and ridge that persisted for another 3 weeks and regressed 2 weeks after laser (n=1). The eyes that received bevacizumab alone (3) did not show any abnormal vascularization at 56 weeks of PMA or beyond.ConclusionsThe retinal vascularization following IVB was different than normal in terms of its time, speed, and morphology; few of these changes are first to be reported in the literature (Medline search) and warrants further studies. PMID:26584796

  10. Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus

    Broe, Rebecca; Rasmussen, Malin L; Frydkjaer-Olsen, Ulrik;


    AIMS/HYPOTHESIS: Fractal analysis of the retinal vasculature provides a global measure of the complexity and density of retinal vessels summarised as a single variable: the fractal dimension. We investigated fractal dimensions as long-term predictors of microvasculopathy in type 1 diabetes. METHODS......: We included 180 patients with type 1 diabetes in a 16 year follow-up study. In baseline retinal photographs (from 1995), all vessels in a zone 0.5-2.0 disc diameters from the disc margin were traced using Singapore Institute Vessel Assessment-Fractal image analysis software. Artefacts were removed by...... a certified grader, and fractal dimensions were calculated using the box-counting method. At follow-up (in 2011), diabetic neuropathy, nephropathy and proliferative retinopathy were assessed and related to baseline fractal dimensions in multiple regressions adjusted for sex and baseline age...

  11. Retinal vasculature classification using novel multifractal features

    Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms. (paper)

  12. Retinal vein and artery occlusions

    Christiansen, Christine Benn; Lip, Gregory Y. H.; Lamberts, Morten;


    Retinal vascular occlusions may constitute an independent risk factor for stroke in patients with atrial fibrillation.......Retinal vascular occlusions may constitute an independent risk factor for stroke in patients with atrial fibrillation....

  13. The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles.

    Sheikpranbabu, Sardarpasha; Kalishwaralal, Kalimuthu; Lee, Kyung-Jin; Vaidyanathan, Ramanathan; Eom, Soo Hyun; Gurunathan, Sangiliyandi


    The increased permeability of the blood-retinal barrier is known to occur in patients with diabetes, and this defect contributes to retinal edema. This study aimed to determine the effects of silver nanoparticles (Ag-NPs) on advanced glycation end-products (AGEs)-induced endothelial cell permeability. Cultured porcine retinal endothelial cells (PRECs) were exposed to AGE-modified bovine serum albumin (AGE-BSA) and the endothelial cell permeability was detected by measuring the flux of RITC-dextran across the PREC monolayers. We found that AGE-BSA increased the dextran flux across a PREC monolayer and Ag-NPs blocked the solute flux induced by AGE-BSA. In order to understand the underlying signaling mechanism of Ag-NPs on the inhibitory effect of AGE-BSA-induced permeability, we demonstrated that Ag-NPs could inhibit the AGE-BSA-induced permeability via Src kinase pathway. AGE-BSA also increased the PREC permeability by stimulating the expression of intracellular adhesion molecule-1 (ICAM-1) and decreased the expression of occludin and ZO-1. Further, Ag-NPs inhibited the AGE-BSA-induced permeability by increased expression of tight junction proteins occludin and ZO-1, co-incident with an increase in barrier properties of endothelial monolayer. Together, our results indicate that Ag-NPs could possibly act as potent anti-permeability molecule by targeting the Src signaling pathway and tight junction proteins and it offers potential targets to inhibit the ocular related diseases. PMID:19963272

  14. PDMS content affects in vitro hemocompatibility of synthetic vascular grafts.

    Spiller, Dario; Losi, Paola; Briganti, Enrica; Sbrana, Silverio; Kull, Silvia; Martinelli, Ilaria; Soldani, Giorgio


    An unsolved problem when employing small-diameter vascular grafts for aorto-coronary by-pass and peripheral reconstruction is the early thrombotic occlusion. The PEtU-PDMS is a new elastomeric material, composed of poly(ether)urethane and polydimethylsiloxane, synthesized to realize grafts with improved hemocompatibility characteristics. In order to investigate the effect of PDMS content on hemocompatibility, three different percentages of PDMS containing grafts (10, 25 and 40) were evaluated. Grafts realized with Estane 5714-F1 and silicone medical grade tubes were used as references. The hemocompatibility was investigated by an in vitro circuit in which human anticoagulated blood was circulated into grafts by a peristaltic pump modified to obtain a passive flow. For each experiment, 40 cm length graft was closed into a circular loop and put in rotation for 2 h at 37 degrees C. At the end of the experiments different parameters regarding platelet adhesion and activation were evaluated: circulating platelets count, beta-thromboglobulin release, platelet CD62P expression and amount of monocyte-platelet conjugates. PEtU-PDMS grafts with 25 and 40% of PDMS induced the lowest platelet adhesion, plasma level of beta-TG and amount of monocyte-platelet conjugates. No significative variations were observed in CD62P expression. In conclusion, PDMS content significatively affects blood-graft surface interaction, in fact higher PDMS percentage containing grafts showed the best in vitro hemocompatibility. PMID:17268875

  15. Risk Factors and Treatment Strategies in Patients With Retinal Vascular Occlusions.

    Chapin, John; Carlson, Karen; Christos, Paul J; DeSancho, Maria Teresa


    Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) cause significant visual impairment. The role of thrombophilia and cardiovascular testing is uncertain, and optimal treatment strategies have not been determined. We reviewed medical records of 39 patients with RVO and RAO (23 women and 16 men). Thrombophilia and cardiovascular evaluations were performed and outcomes were reviewed. In all, 24 (61.5%) patients had at least 1 thrombophilia. Elevated factor VIII levels were found in RVO (n = 5) but not in RAO. There are no other significant differences in thrombophilias in RVO compared to those in RAO. Most patients had hypertension(41.2% RAO and 55% RVO) and hyperlipidemia (35.5% RAO and 81.8% RVO). In all, 4 women were using oral contraceptives, 2 were pregnant or postpartum. Follow-up data was available for 28 patients (13 RAO, 15 RVO). Nineteen were treated with aspirin, four with warfarin, and one with low molecular weight heparin. Eight patients reported improvement in vision at time of follow-up (5 RAO, 3 RVO). Multiple risk factors are associated with RVO and RAO, and a complete assessment should include thrombophilia and cardiovascular studies. PMID:24335246

  16. Melatonin differentially affects vascular blood flow in humans

    Cook, Jonathan S.; Sauder, Charity L.; Ray, Chester A.


    Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial...


    Purpose:Agricultural and occupational exposures to the fungicides benomyl and captan and the insecticide fenthion have been associated with retinal degeneration. Exposure to insecticides has also been associated with pigmentary changes of the retina. Because retinal degeneration ...

  18. Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV?

    Sophia Pathai

    Full Text Available OBJECTIVES: HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa. METHODS: Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye. RESULTS: The median age was 40 years (IQR: 35-48 years. Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART (median duration, 58 months, their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15. Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07. Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm 6 years, p-trend = 0.02, and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05. HIV-related venular changes were not detected. CONCLUSIONS: Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV

  19. Systemic immunotherapy delays photoreceptor cell loss and prevents vascular pathology in Royal College of Surgeons rats

    Adamus, Grazyna; Wang, Shaomei; Kyger, Madison; Worley, Aneta; Lu, Bin; Burrows, Gregory G.


    Purpose Degenerative retinopathies, including retinitis pigmentosa, age-related retinal degeneration, autoimmune retinopathy, and related diseases affect millions of people around the world. Currently, there is no effective treatment for most of those diseases. We investigated systemic recombinant T-cell receptor ligand (RTL) immunotherapy for preventing retinal degeneration and vascular damage in the Royal College of Surgeons (RCS) rat model of retinal degeneration. Methods RCS rats were tre...

  20. Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Pedersen, Knud;


    . In a randomly selected eye of each patient, Fd was calculated using SIVA-Fractal, a specialized semiautomatic software. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral-domain optical coherence tomography (OCT) and by a RETI-scan multifocal ERG (mf-ERG) system in rings one to...... ETDRS levels were 10 (42.7%), 20 (35.0%), and 35 (22.3%), respectively. Fd correlated inversely with mf-ERG implicit time of ring one (r = -0.25, P = 0.01) and present diabetic neuropathy (P = 0.02), and positively with OCT ganglion cell layer (GCL) thickness (r = 0.20, P = 0.04). In a multivariable...... linear regression model, Fd was associated with mf-ERG implicit time of ring one (coefficient -0.0021/ms, P = 0.040) and the presence of diabetic neuropathy (coefficient -0.0209 for neuropathy present versus absent, P = 0.041). Conclusions: In patients with T2DM and no or minimal DR, independent...

  1. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function.

    Maria Tikhonenko

    Full Text Available OBJECTIVE: The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs. We propose that n-3 polyunsaturated fatty acid (PUFA deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. RESEARCH DESIGN AND METHODS: Type 2 diabetic rats on control or docosahexaenoic acid (DHA-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL-1β, IL-6, intracellular adhesion molecule (ICAM-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. RESULTS: DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. CONCLUSIONS: In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.

  2. Vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide

    ZHANG Xiao-ling; WEN Liang; CHEN Yan-jiong; ZHU Yi


    Background The vascular endothelial growth factor (VEGF) is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 (ICAM-1) is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells (ECs) is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs.Methods Bovine retinal ECs (BRECs) were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF (100 ng/ml) and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase (eNOS) were detected using Western blotting. Griess reaction was used to detect nitric oxide (NO).Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C (PKC) altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase (PI3K) or reactive oxygen species (ROS) significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased.Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.

  3. External Beam Radiotherapy for Head and Neck Cancers Is Associated with Increased Variability in Retinal Vascular Oxygenation

    Higginson, Daniel S.; Sahgal, Alok; Lawrence, Michael V.; Moyer, Sarah; Stefanescu, Mihaela; Willson, Adam K.; Qaqish, Bahjat; Zanation, Adam; Marks, Lawrence B.; Garg, Seema; Chera, Bhishamjit S.


    Background Radiation retinopathy is a possible post-treatment complication of radiation therapy. The pathophysiologic mechanism is hypothesized to be microvascular in origin, but evidence is limited. In an effort to study retinal oxygenation in these patients, we herein evaluate the repeatability and variability of retinal oximetry measurements in subjects who had previously received radiation and make comparisons to a cohort of unirradiated subjects. Methods Using retinal oximetry, a non-inv...

  4. Cotton wool spots as possible indicators of retinal vascular pathology in ocular lyme borreliosis.

    Klaeger, Andres J; Herbort, Carl P


    Lyme borreliosis is an underdiagnosed infectious disease caused by a spirochete and transmitted by certain Ixodes ticks. In Lyme disease diagnostic problems are still discussed extensively as the laboratory workup is not standardized and a positive antibody result is not proof of active infection. It is therefore important to appreciate all clinical signs that can prompt us to the diagnostic investigation of Lyme borreliosis. We present a case of a woman with Lyme borreliosis and recurrent unilateral anterior uveitis in her right eye for 2 years, who developed cotton wool spots (CWS) in her left eye, followed by acute and recurrent anterior uveitis in this second eye. An extensive general examination, including blood coagulopathies and ultrasound of the carotid arteries, did not reveal any pathology. The CWS resolved within a few months. The recurrent anterior uveitis could be controlled by topical steroids. After treatment with 2 g of i.v. ceftriaxone for 3 weeks, she remained free of recurrences for 1 year of observation time. CWS can be the first clinical sign of ocular vascular pathology and/or uveitis. Further investigation will be necessary to confirm the relationship between CWS and ocular borreliosis. In patients with otherwise unexplained CWS, the possibility of an infection with borreliosis should be ruled out carefully. PMID:18854948

  5. Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy

    Andrey G Shchuko


    Full Text Available Purpose: To analyze the change in the concentration of intraocular cytokines (ICs in patients with retinal vein occlusion (RVO before and after intravitreal ranibizumab therapy (IVR, and to find the correlations of IC with clinical activity of RVO and efficiency of treatment. Materials and Methods: Forty-four patients aged 46–79 years old (mean age: 60.7 ± 7.5 years old with RVO and macular edema (18 patients – with central RVO, 26 – with branch RVO treated with IVR were included into the study. The concentrations of 27 cytokines were simultaneously measured in aqueous humor by flow fluorometry using Bio-Plex Pro Human Cytokine Panel, 27-Plex (Bio-Rad Laboratories, USA at baseline and after the first IVR. Control group consisted of 20 age-matched patients. Results: The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL-13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted were significantly (P < 0.05 different compared to control and significantly (P < 0.05 changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -"effective" and the second - "partially effective" therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group. Conclusion: The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes.

  6. Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion


    Retinal vein occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity (VA) in this retinal vascular disorder. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection route. The most widely injected...

  7. Vaccination with a mutated variant of human Vascular Endothelial Growth Factor (VEGF) blocks VEGF-induced retinal neovascularization in a rabbit experimental model.

    Morera, Yanelys; González, Rafael; Lamdan, Humberto; Pérez, Lincidio; González, Yorlandis; Agüero, Judith; Castro, Jorge; Romero, Juan C; Etchegoyen, Ana Yansy; Ayala, Marta; Gavilondo, Jorge V


    Vascular Endothelial Growth Factor (VEGF) is a key driver of the neovascularization and vascular permeability that leads to the loss of visual acuity of eye diseases like wet age-related macular degeneration, diabetic macular edema, and retinopathy of premature. Among the several anti-VEGF therapies under investigation for the treatment of neovascular eye diseases, our group has developed the vaccine candidate CIGB-247-V that uses a mutated form of human VEGF as antigen. In this work we evaluated if the vaccine could prevent or attenuate VEGF-induced retinal neovascularization in the course of a rabbit eye neovascularization model, based on direct intravitreal injection of human VEGF. Our experimental findings have shown that anti-VEGF IgG antibodies induced by the vaccine were available in the retina blood circulation, and could neutralize in situ the neovascularization effect of VEGF. CIGB-247-V vaccination proved to effectively reduce retinal neovascularization caused by intravitreal VEGF injection. Altogether, these results open the way for human studies of the vaccine in neovascular eye syndromes, and inform on the potential mechanisms involved in its effect. PMID:24675387

  8. Image enhancement for retinal vascular based on fractional differential%基于分数阶微分的视网膜血管图像增强

    车进; 师一帅; 张成


    Starting from the enhanced ability of fractional differential to image details, the paper analyzes the mechanism of fractional differential, then constructs an approximate sixteen directions fractional differential template according to vector synthesis theorem and fractional differential difference function deduced by fractional calculus G-L definition, and uses the template to enhance retinal vascular image. The experimental results show, in response to those retinal vascular images which have rich textural detail information, fractional differential outperforms integral differential operation to extract the textural detail information in smooth region without too much gray scale change.%从分数阶微分对图像纹理细节的增强能力出发,对分数阶微分的机理进行分析,根据分数阶微积分的G-L定义推导出的差分公式与向量合成定理构建了近似的16方向分数阶微分模板,并将其应用于视网膜血管图像增强中.实验结果表明,对于纹理细节信息丰富的视网膜血管图像而言,分数阶微分对灰度变化不大的平坦区域中的纹理细节信息的提取效果明显优于整数阶微分运算.

  9. Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion

    Noergaard, Michael Hove; Bach-Holm, Daniella; Scherfig, Erik;


    To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs.......To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs....

  10. Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

    T. Bruder-Nascimento


    Full Text Available Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load. One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im. Acute immobilization stress (2 h was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g: sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

  11. Evaluation of geometric features as biomarkers of diabetic retinopathy for characterizing the retinal vascular changes during the progression of diabetes

    Leontidis, Georgios; Al-Diri, Bashir; Wigdahl, Jeffrey; Hunter, Andrew


    Diabetic retinopathy (DR) has been widely studied and characterized. However, until now, it is unclear how different features, extracted from the retinal vasculature, can be associated with the progression of diabetes and therefore become biomarkers of DR. In this study, a comprehensive analysis is presented, in which four groups were created, using eighty fundus images from twenty patients, who have progressed to DR and they had no history of any other diseases (e.g. hypertension or glaucoma...

  12. Hereditary retinal eye diseases in childhood and youth affecting the central retina

    Martin M Nentwich


    Classic examinations for patients suffering from hereditary retinal dystrophies of the central retina are funduscopy - also using red-free light - visual-field tests, electrophysiologic tests as electro-retinogram [ERG] and multifocal ERG and tests evaluating color vision. Recently, new imaging modalities have been introduced into the clinical practice. The significance of these new methods such as high-resolution spectral-domain optic coherence tomography [SD-OCT] and fundus autofluorescence will be discussed as well as "next generation sequencing" as a new method for the analysis of genetic mutations in a larger number of patients.

  13. In search of underlying mechanisms and potential drugs of melphalan-induced vascular toxicity through retinal endothelial cells using bioinformatics approach.

    Yang, Yang; Xing, Yiqiao; Liang, Chaoqun; Hu, Liya; Xu, Fei; Mei, Qi


    We aimed to explore molecular mechanism and drug candidates of vascular toxicities associated with melphalan after treating human retinal endothelial cells (RECs). GSE34381 microarray data was firstly downloaded and used to identify the differentially expressed genes (DEGs) in human REC treated with melphalan vs. untreated cells by limma package in R language. The transcription network was constructed based on TRANSFAC database and the top five transcription factors (TFs) were select with a measure of regulatory impact factor, followed by the construction of function modules. Gene ontology enrichment analyses were performed to explore the enriched functions. Connectivity Map analysis was conducted to predict the potential drugs overcoming the melphalan's actions on REC. Totally, 75 DEGs were identified, including 70 up-regulated and five down-regulated genes. Transcription network with 1311 nodes and 1875 edges was constructed and the top five TFs were CREM, MYC, FLI1, NF-κB1, and JUN. Functional modules indicated that NF-κB1 and MYC were the important nodes. The upregulated genes as well as the genes involved in the modules mainly participated in biological process of immune response, cell proliferation, and cell motion. Five small molecules were predicted to be potential drug candidates, including doxorubicin, fipexide, daunorubicin, tiabendazole, and GW-8510. Based on these results, we speculate that NF-κB1 and MYC might involve in the molecular mechanism of vascular toxicity induced by melphalan through regulating their target genes. Five small molecules might be drug candidates to overcome the melphalan-induced vascular toxicity via targeting to MYC and JUN. PMID:26662105

  14. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J


    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised. PMID:26642749

  15. Rescuing axons from degeneration does not affect retinal ganglion cell death

    S. de Lima


    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  16. The retinal clock is altered in a mouse model of diabetic retinopathy

    HASNA LAHOUAOUI; Christine Coutanson; Mohamed BENNIS


    The mammalian retina contains an endogenous pacemaker that regulates retinal physiology and adjusts daily the temporal phase of the central circadian timing system with environmental time. This entrainment process involves rods, cones and melanopsin-expressing retinal ganglion cells. Diabetic retinopathy is a major cause of blindness and visual impairment that affects up to 90% of patients with diabetes. Although vascular damage is considered the first clinical sign of retinopathy, several ...

  17. Retinal oximetry

    Sveinn Hákon Harðarson 1978


    Purpose Malfunction of retinal blood flow or oxygenation is believed to be involved in various diseases. Among them are retinal vessel occlusions, diabetic retinopathy and glaucoma. Reliable, non-invasive technology for retinal oxygen measurements has been scarce and most of the knowledge on retinal oxygenation comes from animal studies. This thesis describes human retinal oximetry, performed with novel retinal oximetry technology. The thesis describes studies on retinal vessel oxygen satu...

  18. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  19. Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

    Laura eFernández-Sánchez


    Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

  20. Silver nanoparticles inhibit VEGF-and IL-1β-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells

    Park Jongsun


    Full Text Available Abstract The aim of this study is to determine the effects of silver nanoparticles (Ag-NP on vascular endothelial growth factor (VEGF-and interleukin-1 beta (IL-1β-induced vascular permeability, and to detect the underlying signaling mechanisms involved in endothelial cells. Porcine retinal endothelial cells (PRECs were exposed to VEGF, IL-1β and Ag-NP at different combinations and endothelial cell permeability was analyzed by measuring the flux of RITC-dextran across the PRECs monolayer. We found that VEGF and IL-1β increase flux of dextran across a PRECs monolayer, and Ag-NP block solute flux induced by both VEGF and IL-1β. To explore the signalling pathway involved VEGF- and IL-1β-induced endothelial alteration, PRECs were treated with Src inhibitor PP2 prior to VEGF and IL-1β treatment, and the effects were recorded. Further, to clarify the possible involvement of the Src pathways in endothelial cell permeability, plasmid encoding dominant negative(DN and constitutively active(CA form of Src kinases were transfected into PRECs, 24 h prior to VEGF and IL-1β exposure and the effects were recorded. Overexpression of DN Src blocked both VEGF-and IL-1β-induced permeability, while overexpression of CA Src rescues the inhibitory action of Ag-NP in the presence or absence of VEGF and IL-1β. Further, an in vitro kinase assay was performed to identify the presence of the Src phosphorylation at Y419. We report that VEGF and IL-1β-stimulate endothelial permeability via Src dependent pathway by increasing the Src phosphorylation and Ag-NP block the VEGF-and IL-1β-induced Src phosphorylation at Y419. These results demonstrate that Ag-NP may inhibit the VEGF-and IL-1β-induced permeability through inactivation of Src kinase pathway and this pathway may represent a potential therapeutic target to inhibit the ocular diseases such as diabetic retinopathy.

  1. Probabilistic retinal vessel segmentation

    Wu, Chang-Hua; Agam, Gady


    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  2. Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

    Resendes, A R; Segalés, J


    Vascular lesions and their association with porcine circovirus type 2 (PCV2) were evaluated in multiple organs from 10 pigs affected with PCV2-systemic disease (PCV2-SD). Animals had vascular lesions in multiple organs, consisting of lymphohistiocytic lymphangitis and/or phlebitis, mild to severe necrotizing arteritis, and thrombosis within splenic arterioles and choroid plexus capillaries. Variable amounts of PCV2 nucleic acid detected by in situ hybridization were present within endothelial cells, tunica media myocytes, and perivascular and/or intralesional inflammatory cell infiltrates. PCV2 nucleic acid was detected within endothelial cells of both lymphatic and blood vessels without lesions in the associated tissues. Necrotizing arteritis was principally present in lymph nodes and kidney and consisted of degeneration, necrosis, and pyknosis of myocytes, often with intracytoplasmic, brightly eosinophilic inclusion bodies that were strongly positive for PCV2 nucleic acid. Segmental or circumferential fibrinoid necrosis was mainly present in vessels of the lymph node, spleen, and choroid plexus and was variably associated with PCV2 nucleic acid. Severe lymphangitis associated with strong intralesional PCV2 labeling was frequently detected within the mesenteric and mediastinal lymph nodes and the lamina propria of the ileum. In most tissues, medium and large lymphatics and/or veins often had disruption of the intima and mild mononuclear inflammatory cell infiltration that was variably associated with PCV2 nucleic acid. The present study indicates that vasculitis is a frequent finding in natural cases of PCV2-SD and that PCV2 may have a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as endothelium. PMID:24963088

  3. Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

    Johanna M Walz

    Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

  4. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema

    Kiss S


    .03; IVTA, 3.3 versus 3.0, P<0.05.Conclusion: During the study period (2008–2011, bevacizumab was the main anti-VEGF therapy used in clinical practice for BRVO, CRVO, and DME. Patients treated with bevacizumab were monitored less frequently and received fewer injections than patients in major clinical trials of ranibizumab. Keywords: anti-vascular endothelial growth factor, bevacizumab, ranibizumab, diabetic macular edema, retinal vein occlusion, intravitreal

  5. Retinal vessel diameter changes induced by transient high perfusion pressure

    Yin-Ying; Zhao; Ping-Jun; Chang; Fang; Yu; Yun-E; Zhao


    ·AIM: To investigate the effects of transient high perfusion pressure on the retinal vessel diameter and retinal ganglion cells.·METHODS: The animals were divided into four groups according to different infusion pressure and infusion time(60 mm Hg-3min, 60 mm Hg-5min, 100 mm Hg-3min, 100 mm Hg-5min). Each group consisted of six rabbits. The left eye was used as the experimental eye and the right as a control. Retinal vascular diameters were evaluated before, during infusion, immediately after infusion, 5min, 10 min and 30 min after infusion based on the fundus photographs. Blood pressure was monitored during infusion. The eyes were removed after 24 h.Damage to retinal ganglion cell(RGC) was analyzed by histology.·RESULTS: Retina became whiten and papilla optic was pale during perfusion. Measurements showed significant decrease in retinal artery and vein diameter during perfusion in all of the four groups at the proximal of the edge of the optic disc. The changes were significant in the 100 mm Hg-3min group and 100 mm Hg-5min group compared with 60 mm Hg-3min group(P 1=0.025, P 2=0.000).The diameters in all the groups recovered completely after 30 min of reperfusion. The number of RGC)showed no significant changes at the IOP in 100 mm Hg with5 min compared with contralateral untreated eye(P >0.05).·CONCLUSION: Transient fluctuations during infusion lead to temporal changes of retinal vessels, which could affect the retinal blood circulation. The RGCs were not affected by this transient fluctuation. Further studies are necessary to evaluate the effect of pressure during realtime phacoemusification on retinal blood circulation.

  6. Factors affecting the ability of the spectral domain optical coherence tomograph to detect photographic retinal nerve fiber layer defects.

    Harsha L Rao

    Full Text Available To evaluate the ability of normative database classification (color-coded maps of spectral domain optical coherence tomograph (SDOCT in detecting wedge shaped retinal nerve fiber layer (RNFL defects identified on photographs and the factors affecting the ability of SDOCT in detecting these RNFL defects.In a cross-sectional study, 238 eyes (476 RNFL quadrants of 172 normal subjects and 85 eyes (103 RNFL quadrants with wedge shaped RNFL defects of 66 glaucoma patients underwent RNFL imaging with SDOCT. Logistic regression models were used to evaluate the factors associated with false positive and false negative RNFL classifications of the color-coded maps of SDOCT.False positive classification at a p value of <5% was seen in 108 of 476 quadrants (22.8%. False negative classification at a p value of <5% was seen in 16 of 103 quadrants (15.5%. Of the 103 quadrants with RNFL defects, 64 showed a corresponding VF defect in the opposite hemisphere and 39 were preperimetric. Higher signal strength index (SSI of the scan was less likely to have a false positive classification (odds ratio: 0.97, p = 0.01. Presence of an associated visual field defect (odds ratio: 0.17, p = 0.01 and inferior quadrant RNFL defects as compared to superior (odds ratio: 0.24, p = 0.04 were less likely to show false negative classifications.Scans with lower signal strengths were more likely to show false positive RNFL classifications, and preperimetric and superior quadrant RNFL defects were more likely to show false negative classifications on color-coded maps of SDOCT.

  7. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    Svenningsen, Per; Hansen, Pernille B L


    -type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article......Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  8. Interrelationships between the Retinal Neuroglia and Vasculature in Diabetes

    Timothy S. Kern


    Full Text Available For years, diabetic retinopathy has been defined based on vascular lesions, and neural abnormalities were not regarded as important. This review summarizes evidence that the neural retina has important effects on the retinal vasculature under normal conditions, and the interaction between the retinal neuroglial cells and vascular function is altered in diabetes. Importantly, new evidence raises a possibility that abnormalities within retinal neuroglial cells (notably photoreceptors might actually be causing or initiating the vascular disease in diabetic retinopathy.

  9. Cell Swelling Contributes to Thickening of Low-Dose N-methyl-D-Aspartate–Induced Retinal Edema

    Chen, Junjie; Chiang, Chia-Wen; Zhang, Huiying; Song, Sheng-Kwei


    Noninvasive magnetic resonance imaging was performed to detect retinal cell swelling in vivo. Our results demonstrated cell swelling could directly contribute to edematous retinal thickening independent of retinal vascular leakage.

  10. Neovascularização retiniana secundária a obstrução vascular em retinocoroidite por toxoplasmose em paciente HIV positivo: relato de caso Retinal vascular occlusion and neovascularization in acute toxoplasmic retinochoroiditis in a patient with AIDS: case report

    Vânia Ewert


    Full Text Available Apresentar e discutir o caso de paciente infectado pelo HIV, que desenvolveu quadro de obstrução vascular seguido de neovascularização retiniana e de papila, durante o tratamento específico para retinocoroidite por toxoplasmose e que evoluiu com resolução espontânea da neovascularização sem a necessidade de tratamento associado. Paciente com retinocoroidite por toxoplasmose, que após 4 semanas de tratamento específico (sulfadiazina e pirimetamina desenvolveu quadro de obstrução vascular, seguido de neovascularização retiniana, apresentou involução espontânea, não havendo necessidade de fotocoagulação a laser, ou de outro tratamento adicional. As lesões retinianas ativas de toxoplasmose podem cursar com complicações vasculares, mesmo na vigência de tratamento específico, e geralmente apresentam bom prognóstico com regressão espontânea dos neovasos, sem necessidade de tratamentos adicionais.To present a case of an HIV-infected patient, who presented with active chorioretinal inflammatory lesion suggestive of toxoplasmosis, that during the specific treatment developed a retinal vascular occlusion, and adjacent neovascularization. 35-year-old AIDS patient that, presented with toxoplasmic retinochoroiditis and after 4 weeks of the specific therapy (pyrimethamine and sulfadiazine developed a vascular occlusion and retinal neovascularization that healed without the need for phototocoagulation or other adjunctive therapy. This case demonstrates that acute toxoplasmic retinochoroiditis that develops vascular complications may present a good result with the specific treatment without the need for adjunctive therapy.

  11. Rapid regression of exudative maculopathy in idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome after intravitreal ranibizumab.

    Marín-Lambíes, Cristina; Gallego-Pinazo, Roberto; Salom, David; Navarrete, Javier; Díaz-Llopis, Manuel


    The idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome is a rare retinal vascular disorder characterized by multiple leaking aneurysmal dilations, retinal vasculitis, neuroretinitis and peripheral vascular ischemia. Visual loss mainly occurs due to the development of retinal neovascularization and/or exudative maculopathy. Although the treatment of choice has not yet been established, retinal photocoagulation seems to be the best option to control the disease and to prevent its progression. Herein, we report a case of idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome with both retinal neovascularization and macular exudation successfully managed with intravitreal ranibizumab (Lucentis(®)) as adjunctive therapy to retinal photocoagulation. PMID:22949913

  12. Cybersickness provoked by head-mounted display affects cutaneous vascular tone, heart rate and reaction time.

    Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V


    Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology. PMID:26340855

  13. Vascular endothelial growth factor and dexamethasone release from nonfouling sensor coatings affect the foreign body response

    Norton, L.W.; Koschwanez, H.E.; Wisniewski, N.A.; Klitzman, B.; Reichert, W. M.


    Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydro-xyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and...

  14. Retinitis Pigmentosa

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... die. Forms of RP and related diseases include Usher syndrome, Leber’s congenital amaurosis, rod-cone disease, Bardet- ...

  15. Rapid Regression of Exudative Maculopathy in Idiopathic Retinitis, Vasculitis, Aneurysms and Neuroretinitis Syndrome after Intravitreal Ranibizumab

    Marín-Lambíes, Cristina; Gallego-Pinazo, Roberto; Salom, David; Navarrete, Javier; Díaz-Llopis, Manuel


    The idiopathic retinitis, vasculitis, aneurysms and neuroretinitis syndrome is a rare retinal vascular disorder characterized by multiple leaking aneurysmal dilations, retinal vasculitis, neuroretinitis and peripheral vascular ischemia. Visual loss mainly occurs due to the development of retinal neovascularization and/or exudative maculopathy. Although the treatment of choice has not yet been established, retinal photocoagulation seems to be the best option to control the disease and to preve...

  16. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice

    Dilu Feng


    Full Text Available In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE+ and without luminal epithelium (LE− were transplanted from transgenic green-fluorescent-protein-positive (GFP+ donor mice into the dorsal skinfold chamber of GFP− wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE− fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE+ fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE+ lesions compared with LE− lesions. In addition, we found that many GFP+ microvessels grew outside the LE− lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  17. 视网膜血管直径与家族性高胆固醇血症的相关性研究%Retinal vascular caliber and the risk of familial hypercholesterolemia

    高新晓; 孟忻; 蔺洁; 郭佳; 汪军


    目的 探讨视网膜血管直径与家族性高胆固醇血症(FH)的相关性.方法 选取2008年6月至2014年2月于首都医科大学附属北京安贞医院确诊为FH的21例患者为FH组,另外选取38例年龄、性别、血压和血糖相匹配的非FH正常者为对照组.通过彩色眼底照相及计算机辅助软件对视网膜动脉直径(CRAE)、视网膜静脉直径(CRVE)和视网膜动、静脉直径比值(AVR)分别进行测量.比较2组患者视网膜血管直径的测量值,并采用多元线性回归分析视网膜血管直径与FH的相关性.结果 2组患者性别、收缩压、舒张压、空腹血糖比较,差异无统计学意义(P>0.05).与对照组比较,FH组CRAE和AVR数值均明显降低[CRAE:(147 ±6)μm比(150±4)μm,AVR∶(0.65±0.05)比(0.69±0.08)],差异有统计学意义(P<0.05).2组患者的CRVE比较,差异无统计学意义(P=0.90).校正年龄及性别后,AVR减小与FH相关(P =0.03),FH越明显,AVR越小.结论 FH患者的AVR较正常人群减小,视网膜血管直径改变对FH具有一定提示作用.%Objective To examine the relation between retinal vascular caliber and familial hypercholesterolemia (FH).Methods We prospectively recruited 21 cases of FH and 38 control cases with matched age,gender,blood pressure and blood sugar from June 2008 to February 2014.Central retinal artery equivalent (CRAE),central retinal vein equivalent (CRVE) and arteriovenous ratio (AVR) were assessed from baseline retinal photographs using IVAN software.CRAE,CRVE and AVR were compared with the student t test between FH group and controls.Multiple linear regression analysis was performed to evaluate the correlation between retinal vascular caliber and FH.Results CRAE and AVR were decreased in FH group compared with controls[CRAE:(147 ± 6) μm vs (150 ± 4) μm,AVR:(0.65 ± 0.05) vs (0.69 ± 0.08)].The difference between the two groups was significant (P < 0.05).Decreased AVR was associated with FH (P =0.03) after controlling

  18. Bim is Responsible for the Inherent Sensitivity of the Developing Retinal Vasculature to Hyperoxia

    Wang, Shoujian; Park, Sunyoung; Fei, Ping; Sorenson, Christine M.


    Apoptosis plays an important role in development and remodeling of vasculature during organogenesis. Coordinated branching and remodeling of the retinal vascular tree is essential for normal retinal function. Bcl-2 family members, such as bim can not only influence apoptosis, but also cell adhesive and migratory properties essential during vascular development. Here we examined the impact of bim deficiency on postnatal retinal vascularization, as well as retinal neovascularization during oxyg...

  19. Elk3 Deficiency Causes Transient Impairment in Post-Natal Retinal Vascular Development and Formation of Tortuous Arteries in Adult Murine Retinae

    Christine Weinl; Christine Wasylyk; Marina Garcia Garrido; Vithiyanjali Sothilingam; Beck, Susanne C.; Heidemarie Riehle; Christine Stritt; Michel J Roux; Seeliger, Mathias W.; Bohdan Wasylyk; Alfred Nordheim


    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In E...

  20. A residue substitution near the beta-ionone ring of the retinal affects the M substates of bacteriorhodopsin

    Varo, G.; Zimanyi, L.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.


    The switch in the bacteriorhodopsin photocycle, which reorients access of the retinal Schiff base from the extracellular to the cytoplasmic side, was suggested to be an M1----M2 reaction (Varo and Lanyi. 1991. Biochemistry. 30:5008-5015, 5016-5022). Thus, in this light-driven proton pump it is the interconversion of proposed M substates that gives direction to the transport. We find that in monomeric, although not purple membrane-lattice immobilized, D115N bacteriorhodopsin, the absorption maximum of M changes during the photocycle: in the time domain between its rise and decay it shifts 15 nm to the blue relative to the spectrum at earlier times. This large shift strongly supports the existence of two M substates. Since D115 is located near the beta-ionone ring of the retinal, the result raises questions about the possible involvement of the retinal chain or protein residues as far away as 10 A from the Schiff base in the mechanism of the switching reaction.

  1. Risk factor profile in retinal detachment

    Azad Raj


    Full Text Available 150 cases of retinal detachment comprising 50 patients each of bilateral retinal detachment, unilateral retinal detachment without any retinal lesions in the fellow eve and unilateral retinal detachment with retinal lesions in the fellow eye were studied and the various associated risk factors were statistically analysed. The findings are discussed in relation to their aetiological and prognostic significance in the different types of retinal detachment. Based on these observations certain guidelines are offered which may be of value in decision making, in prophylactic detachment surgery. Tractional breaks in the superior temporal quadrant especially when symptomatic. mandate prophylactic treatment. Urgency is enhanced it′ the patient is aphakic. Associated myopia adds to the urgency. The higher incidence of initial right e′ e involvement in all groups suggests a vascular original possibly ischaemic.

  2. Ischemic Retinal Vasculitis and Its Management

    Lazha Talat


    Full Text Available Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behçet’s disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behçet’s disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied.

  3. An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy.

    O'Brien, G


    The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies.

  4. Interrelationships between the Retinal Neuroglia and Vasculature in Diabetes

    Kern, Timothy S.


    For years, diabetic retinopathy has been defined based on vascular lesions, and neural abnormalities were not regarded as important. This review summarizes evidence that the neural retina has important effects on the retinal vasculature under normal conditions, and the interaction between the retinal neuroglial cells and vascular function is altered in diabetes. Importantly, new evidence raises a possibility that abnormalities within retinal neuroglial cells (notably photoreceptors) might act...

  5. Antihypertensive treatment differentially affects vascular sphingolipid biology in spontaneously hypertensive rats.

    Léon J A Spijkers

    Full Text Available BACKGROUND: We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR, is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A(2, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A(2. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. METHODS AND FINDINGS: For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg. The blood pressure lowering was associated with a 20-25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A(2. The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. CONCLUSION: In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions.

  6. Vascular endothelial growth factor signaling affects both angiogenesis and osteogenesis during the development of scleral ossicles.

    Jabalee, James; Franz-Odendaal, Tamara A


    Intramembranous ossification is a complex multi-step process which relies on extensive interactions among bone cells and surrounding tissues. The embryonic vasculature is essential in regulating endochondral ossification; however, its role during intramembranous ossification remains poorly understood, and in vivo studies are lacking. Previous research from our lab on the development of the intramembranous scleral ossicles has demonstrated an intriguing pattern of vascular development in which the areas of future osteogenesis remain avascular until after bone induction has occurred. Such avascular zones are located directly beneath each of the conjunctival papillae, epithelial structures which provide osteogenic signals to the underlying mesenchyme. Here we provide a high-resolution map of the developing vasculature from the time of ossicle induction to mineralization using a novel technique. We show that vegfa is expressed by the papillae and nearby mesenchymal tissue throughout HH 34-37, when vascular growth is taking place, and is down-regulated thereafter. Localized inhibition of Vegf results in expansion of the avascular zone surrounding the implanted papilla and mispatterning of the scleral ossicles. These results demonstrate that Vegf signaling could provide important insights into the complex relationship between bone and vasculature during intramembranous bone development. PMID:26210172

  7. Retinal Detachment

    ... are three different types of retinal detachment: Rhegmatogenous [reg-ma-TAH-jenous]—A tear or break in the retina allows fluid to get under the retina and separate it from the retinal pigment epithelium (RPE), the pigmented cell layer that nourishes the retina. These types of ...

  8. Arginase 2 deficiency reduces hyperoxia-mediated retinal neurodegeneration through the regulation of polyamine metabolism

    S.P. Narayanan; Xu, Z.; Putluri, N; Sreekumar, A; Lemtalsi, T; Caldwell, R W; Caldwell, R B


    Hyperoxia treatment has been known to induce neuronal and glial death in the developing central nervous system. Retinopathy of prematurity (ROP) is a devastating disease in premature infants and a major cause of childhood vision impairment. Studies indicate that, in addition to vascular injury, retinal neurons are also affected in ROP. Using an oxygen-induced retinopathy (OIR) mouse model for ROP, we have previously shown that deletion of the arginase 2 (A2) significantly reduced neuro-glial ...

  9. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography

    Nagiel, Aaron; Freund, K Bailey; Spaide, Richard F;


    CNV adherent to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti...

  10. A single nucleotide polymorphism in the Bax gene promoter affects transcription and influences retinal ganglion cell death

    Sheila J Semaan


    Full Text Available Pro-apoptotic Bax is essential for RGC (retinal ganglion cell death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2JBax+/− mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax−/− mice, but 129B6Bax+/− mice exhibited significant cell loss (similar to wild-type mice. The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T129B6 to CDBA/2J at position −515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53−/− cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA–protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.

  11. Sequential bilateral retinal artery occlusion

    Padrón-Pérez N


    Full Text Available Noel Padrón-Pérez,1 Janny Rosario Aronés,2 Silvia Muñoz,1 Luis Arias-Barquet,1 Jorge Arruga1,31Department of Ophthalmology, Hospital Universitari de Bellvitge, 2Hospital de l'Esperança – Parc de Salut Mar, 3Institut Català de Retina, Barcelona, SpainAbstract: An 86 year old woman experienced a sequential bilateral loss of vision over a period of less than 24 hours. Clinical findings and complementary studies suggested a bilateral atherogenic embolic event. Initially, she presented a superior branch retinal artery occlusion in her right eye followed by a central retinal artery occlusion with cilioretinal artery sparing in her left eye. Some conservative maneuvers performed did not improve visual acuity in the left eye. Supra-aortic Doppler ultrasonography revealed mild right internal carotid artery stenosis and moderate left internal carotid artery stenosis with a small, smooth, and homogeneous plaque. The transthoracic echocardiography showed a severe calcification of the mitral valve with a mild-moderate rim of stenosis. Central retinal artery occlusion and branch retinal artery occlusion are characterized by painless monocular loss of vision. Clinical approach and management attempt to treat the acute event, find the source of the vascular occlusion, and prevent further vascular events from occurring. Giant cell arteritis is a potentially treatable cause of central retinal artery occlusion and should be excluded in every single patient over 50 years old.Keywords: loss of vision, branch retinal artery occlusion, central retinal artery occlusion, Hollenhorst plaque

  12. Presumed toxoplasmic central retinal artery occlusion and multifocal retinitis with perivascular sheathing

    Arai H


    Full Text Available Haruka Arai,1 Tsutomu Sakai,1 Kiichiro Okano,1 Ranko Aoyagi,1 Ayano Imai,2 Hiroshi Takase,2 Manabu Mochizuki,2 Hiroshi Tsuneoka11Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, JapanAbstract: Central retinal artery occlusion (CRAO and multifocal retinitis with perivascular sheathing are rare in ocular toxoplasmosis. We report a case of toxoplasmic CRAO and multifocal retinitis with perivascular sheathing. A healthy 83-year-old male developed left panuveitis. Funduscopic examination of the left eye showed a swollen optic disc and sheathing of the retinal artery with a dense vitreous haze and a white retinal lesion. Serum anti-toxoplasma antibodies were positive in a latex agglutination assay. Vitrectomy was performed to improve visualization of the retinal lesions and for examination of causative microorganisms. A postoperative fundus examination revealed CRAO with optic disc involvement and multifocal retinitis with perivascular sheathing. Qualitative multiplex polymerase chain reaction detected the Toxoplasma gondii B1 gene in ocular fluid from both the aqueous and vitreous humor. The presumed diagnosis of ocular toxoplasmosis was made and treatment was started with prednisone and acetylspiramycin with subsequent improvement. Two months later, the patient developed active retinochoroiditis in the left eye. After 6 weeks of anti-toxoplasma therapy, the disease involuted. Retinal vascular occlusions and multifocal retinitis with perivascular sheathing are rare in toxoplasmosis. This is the first case report of toxoplasmic CRAO and multifocal retinitis with perivascular sheathing. The diagnosis of ocular toxoplasmosis should be considered in patients with retinal artery occlusions and multifocal retinitis with perivascular sheathing associated with inflammation.Keywords: ocular toxoplasmosis, toxoplasma retinochoroiditis




    Full Text Available Retinal vein occlusion is the most common retinal occlusive disorder encountered by Ophthalmologists and is usually associated with a variable amount of visual loss. This is the second most common retinal vascular disease next to diabetic retinopathy. Liebreich initially described dramatic obstruction of veins as retinal apoplexy. Leber ( 1 (1877 reported the first case of BRVO and called it Hem orrhagic retinitis. RVO most commonly affects the venous blood supply of the entire retina (CRVO or a quadrant drained by one of the branches (BRVO or less commonly the superior or inferior half of the retina alone is affected (HCRVO. For discussion and management purpose RVO is broadly classified into six clinical entities includes (1 Non - ischemic CRVO (2 Ischemic CRVO (3 Non ischemic HCRVO (4Ischemic HCRVO (5 Major BRVO (6Macular BRVO. So much of confusion still exists regarding its natural histo ry, degree of severity, management and its progression. The clinical study of RVO is taken up mainly with a view to study the importance of systemic risk factors in etiopathogenisis of RVO, to study the clinical features and effectiveness of treatment in m odification of the natural course and complications of RVO. Depending on type of venous occlusion patient may present with loss of central vision frequently noticed on waking up in the morning, or field contraction, erythropsia, floates, black spots. Episo des of amaurosis fugax lasts for minutes to hours may be present. There may be metamor - phopsia. Signs of decreased visual acuty, RAPD, visual field defects are observed. Fundus picture shows Retinal hemorrhages distributed based on type of venous occlusion . In ischemic CRVO the picture shows “berries on a twig”. Various sequel & complications include macular edema, anterior segment and retinal neovascularisation, vitreous hemorrhage, retinal detachment may be encountered. Various risk factors include Hypert ension, Diabetes, Hyper lipidemia, IHD

  14. Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome

    GENG Shuang; YE Jun-jie; ZHAO Jia-liang; LI Tai-sheng; HAN Yang


    Background Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS.Methods It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4+ T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 μg) were performed in 4 eyes (2 patients).Results Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque.Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4+ T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6±25.3) ×106/L (range,(0-85) × 106/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed.Conclusions CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

  15. Hypoxia and the Presence of Human Vascular Endothelial Cells Affect Prostate Cancer Cell Invasion and Metabolism

    Ellen Ackerstaff


    Full Text Available Tumor progression and metastasis are influenced by hypoxia, as well as by interactions between cancer cells and components of the stroma, such as endothelial cells. Here, we have used a magnetic resonance (MRcompatible invasion assay to further understand the effects of hypoxia on human prostate cancer cell invasion and metabolism in the presence and absence of human umbilical vein endothelial cells (HUVECs. Additionally, we compared endogenous activities of selected proteases related to invasion in PC-3 cells and HUVECs, profiled gene expression of PC-3 cells by microarray, evaluated cell proliferation of PC-3 cells and HUVECs by flow cytometry, under hypoxic and oxygenated conditions. The invasion of less-invasive DU-145 cells was not affected by either hypoxia or the presence of HUVECs. However, hypoxia significantly decreased the invasion of PC-3 cells. This hypoxia-induced decrease was attenuated by the presence of HUVECs, whereas under oxygenated conditions, HUVECs did not alter the invasion of PC-3 cells. Cell metabolism changed distinctly with hypoxia and invasion. The endogenous activity of selected extracellular proteases, although altered by hypoxia, did not fully explain the hypoxia-induced changes in invasion. Gene expression profiling indicated that hypoxia affects multiple cellular functions and pathways.

  16. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma.

    Zhang, Kang; Zhang, Liangfang; Weinreb, Robert N


    Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities. PMID:22699774

  17. Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi


    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  18. Retinal vein occlusion in Benin City, Nigeria

    Uhumwangho, Odarosa M.; Darlingtess Oronsaye


    Background: Retinal vein occlusion (RVO) is the most common occlusive retinal vascular disorder and results in varying degrees of visual loss. Aim: To determine the pattern of presentation, risk factors, and treatment outcomes in a group of patients with RVO seen in a tertiary hospital in Nigeria. Materials and Methods: Medical records of patients who presented to the University of Benin Teaching Hospital, Benin City, Nigeria in whom a diagnosis of RVO was made over a 5 years period were revi...

  19. Combined branch retinal vein and artery occlusion in toxoplasmosis.

    Aggio, Fabio Bom; Novelli, Fernando José de; Rosa, Evandro Luis; Nobrega, Mário Junqueira


    A 22-year-old man complained of low visual acuity and pain in his left eye for five days. His ophthalmological examination revealed 2+ anterior chamber reaction and a white, poorly defined retinal lesion at the proximal portion of the inferotemporal vascular arcade. There were retinal hemorrhages in the inferotemporal region extending to the retinal periphery. In addition, venous dilation, increased tortuosity, and ischemic retinal whitening along the inferotemporal vascular arcade were also observed. A proper systemic work-up was performed, and the patient was diagnosed with ocular toxoplasmosis. He was treated with an anti-toxoplasma medication, and his condition slowly improved. Inferior macular inner and middle retinal atrophy could be observed on optical coherence tomography as a sequela of ischemic injury. To our knowledge, this is the first report of combined retinal branch vein and artery occlusion in toxoplasmosis resulting in a striking and unusual macular appearance. PMID:27463632

  20. Reliability of retinal vessel calibre measurements using a retinal oximeter

    Heitmar, Rebekka; Kalitzeos, Angelos A.


    Background Summarised retinal vessel diameters are linked to systemic vascular pathology. Monochromatic images provide best contrast to measure vessel calibres. However, when obtaining images with a dual wavelength oximeter the red-free image can be extracted as the green channel information only which in turn will reduce the number of photographs taken at a given time. This will reduce patient exposure to the camera flash and could provide sufficient quality images to reliably measure vessel...

  1. Amyloidosis in Retinal Neurodegenerative Diseases

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica


    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  2. Acquired retinal folds in the cat.

    MacMillan, A D


    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  3. 联合方法治疗新生血管性青光眼疗效观察%Compound T rabeculectomy and Retinal Photocoagulation and Vitreous Injection Ranibizumab in the M anagement of New Vascular Glaucoma

    林芳; 齐美华; 赵静


    Objective To comparatively evaluate the efficacy and safety profiles of compound trabeculecto-my and Retinal photocoagulation and Vitreous injection Ranibizumab in the management of New vascular glauco-ma .Method Clinical records of 8 patients (8 eyes) with New vascular glaucoma secondary to RVO whose fun-dus oculi can be watched to be treated with Retinal laser photocoagulation first the pathants were threated with Retinal laser photocoagulation ,the second were Vitreous injection Ranibizumab seven days with compound tra-beculectomy after surgery ,according to patients iop and Anterior chamber to teach patients to learning Eye mas-sage?Record visions ,central macular thickness(CM T ) ,intraocular pressure(IOP) ,the degrade of Retinal neo-vascularization of fundus oculi and new vessels changes of iris and angles in Preoperative and postoperative 3 months ,6 months ,1 2 months .Result The Vision:3 months:(0 .0 4 ± 0 .0 4 ) ,6 months:(0 .0 6 ± 0 .0 5 ) ,1 2 months:(0 .0 5 ± 0 .0 4 ) ,4 eye’s Vision were improved 3 eye’s Vision werenot improved .The one eye is No light perception .IOP:3 months:(1 3 .2 4 ± 2 .2 3 )mmhg ,6 months:(1 5 .4 ± 2 3 .4 2 )mmhg ,1 2 months:(1 8 .2 5 ± 3 .1 5 ) mmhg ,6 patients can controled IOP under 2 1 mmhg ,postoperative one patient iop can be controled in normal in first 3 months ,give Alphagan eye water in rising to 2 1 mmhg of iop ,iop can be control in 1 8 mmhg ,6 months lat-er the iop rise to 1 9 mmhg ,in 9 months the iop rised to 2 1 mmhg ,Brinzolamide eye water was used ,iop can be control in 2 0 mmhg ,in 1 2 months ,iop is 2 2 mmhg ,2 2 mmhg ,in Process ,the patient Supplement Retinal photo-coagulation twice new vessels changes of iris and angles:5 cases degrade ,3 cases Reduce ,FFA :Capillary zone de-grade of 5 cases;Capillary zone degrade of 3 cases in Supplement Retinal laser photocoagulation ,CM T :Before treatment and1 week ,2 weeks ,4 weeks ,8 weeks ,1 2 weeks after Vitreous cavity injection was:(4 4 0 .3 6 ± 5 0

  4. Retinal vein occlusion

    Central retinal vein occlusion; Branch retinal vein occlusion; CRVO; BRVO ... Retinal vein occlusion is most often caused by hardening of the arteries ( atherosclerosis ) and the formation of a blood clot. Blockage ...

  5. Retinitis pigmentosa

    Hamel Christian


    Full Text Available Abstract Retinitis pigmentosa (RP is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms. Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema, and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis.

  6. Current perspectives of herpesviral retinitis and choroiditis.

    Madhavan, H N; Priya, K; Biswas, J


    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  7. Retinal vein occlusion: current treatment.

    Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco


    Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. PMID:20938213

  8. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

    Hellstrom, Ann; Perruzzi, Carole; Ju, Meihua; Engström, Eva; Hård, Anna-Lena; Liu, Jun-Li; Albertsson-Wikland, Kerstin; Carlsson, Björn; Niklasson, Aimon; Sjödell, Lena; LeRoith, Derek; Senger, Donald R.; Smith, Lois E. H.


    Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for e...

  9. RNA-binding protein Hermes/RBPMS inversely affects synapse density and axon arbor formation in retinal ganglion cells in vivo.

    Hörnberg, Hanna; Wollerton-van Horck, Francis; Maurus, Daniel; Zwart, Maarten; Svoboda, Hanno; Harris, William A; Holt, Christine E


    The RNA-binding protein Hermes [RNA-binding protein with multiple splicing (RBPMS)] is expressed exclusively in retinal ganglion cells (RGCs) in the CNS, but its function in these cells is not known. Here we show that Hermes protein translocates in granules from RGC bodies down the growing axons. Hermes loss of function in both Xenopus laevis and zebrafish embryos leads to a significant reduction in retinal axon arbor complexity in the optic tectum, and expression of a dominant acting mutant Hermes protein, defective in RNA-granule localization, causes similar defects in arborization. Time-lapse analysis of branch dynamics reveals that the decrease in arbor complexity is caused by a reduction in new branches rather than a decrease in branch stability. Surprisingly, Hermes depletion also leads to enhanced early visual behavior and an increase in the density of presynaptic puncta, suggesting that reduced arborization is accompanied by increased synaptogenesis to maintain synapse number. PMID:23785151

  10. The implication of omega-3 polyunsaturated fatty acids in retinal physiology

    Acar Niyazi


    Full Text Available Neuronal tissues such as the retina and the brain are characterized by their high content in phospholipids. In the retina, phospholipids can account for until 80% of total lipids and are mainly composed by species belonging to phosphatidyl-choline and phosphatidyl-ethanolamine sub-classes. Within fatty acids esterified on retinal phospholipids, omega-3 PUFAs are major components since docosahexaenoic acid (DHA can represent until 50% of total fatty acids in the photoreceptor outer segments. For long time, DHA is known to play a major role in membrane function and subsequently in visual processes by affecting permeability, fluidity, thickness and the activation of membrane-bound proteins. Today, more and more studies show that PUFAs from the omega-3 series may also operate as protective factors in retinal vascular and immuno-regulatory processes, in maintaining the physiologic redox balance and in cell survival. They may operate within complex systems involving eicosanoids, angiogenic factors, inflammatory factors and matrix metalloproteinases. This new and emerging concept based on the interrelationship of omega-3 PUFAs with neural and vascular structure and function appears to be essential when considering retinal diseases of public health significance such as age-related macular degeneration.

  11. Vascular Cures

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  12. Aggressive retinal astrocytoma associated with tuberous sclerosis

    Tomida M


    Full Text Available Machiko Tomida,1 Yoshinori Mitamura,1 Takashi Katome,1 Hiroshi Eguchi,1 Takeshi Naito,1 Takayuki Harada21Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 2Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: We report the case of a patient with an aggressive retinal astrocytoma accompanied with macular edema and neovascular vessels, who was initially treated with intravitreal bevacizumab injections. A 24-year-old male presented to our clinic complaining of visual disturbance in his right eye. At 8 years of age, he had been diagnosed as having tuberous sclerosis complex. Fundus examination demonstrated a retinal tumor accompanied with marked neovascular vessels on the surface, retinal hemorrhage, and macular edema. After six monthly intravitreal bevacizumab injections, fundus examination demonstrated marked regression of the macular edema and neovascular vessels. Two months later, a vitreous hemorrhage developed which necessitated pars plana vitrectomy. After additional intravitreal bevacizumab injection for preventing intraoperative bleeding, vitrectomy with endophotocoagulation for the tumor was performed. The vitreous sample was obtained during vitrectomy, and we measured the vascular endothelial growth factor concentration by enzyme-linked immunosorbent assay. The surgically removed epiretinal neovascular membrane and biopsied retinal tumor expressed vascular endothelial growth factor, although several intravitreal bevacizumab injections led to a vitreous vascular endothelial growth factor concentration of undetectable levels. The clinical course and immunohistochemical analyses indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat the aggressive retinal astrocytoma with macular edema and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal

  13. Arginase 2 deletion reduces neuro-glial injury and improves retinal function in a model of retinopathy of prematurity.

    Subhadra P Narayanan

    Full Text Available BACKGROUND: Retinopathy of prematurity (ROP is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2 in retinal neuro-glial cell injury in the mouse model of ROP. METHODS AND FINDINGS: Studies were performed using wild type (WT and A2 knockout (A2-/- mice exposed to Oxygen Induced Retinopathy (OIR. Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling and Western blotting. Electroretinography (ERG was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the mitochondrial protein Bim were markedly increased in WT OIR retinas compared to controls, whereas the pro-survival Mitochondrial protein BCL-xl was reduced. These alterations were largely blocked in the A2-/- OIR retina. CONCLUSIONS: Our data implicate A2 in neurodegeneration during ROP. Deletion of A2 significantly improves neuronal survival and function, possibly through the regulation of mitochondrial membrane permeability mediated apoptosis during retinal ischemia. These molecular events are associated with

  14. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M Elizabeth


    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  15. Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.

    Boneva, S K; Groß, T R; Schlecht, A; Schmitt, S I; Sippl, C; Jägle, H; Volz, C; Neueder, A; Tamm, E R; Braunger, B M


    Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina. PMID:27026593

  16. The factors affecting outcome after non-vascular bone grafting and internal fixation for nonunion of the scaphoid.

    Ramamurthy, C; Cutler, L; Nuttall, D; Simison, A J M; Trail, I A; Stanley, J K


    This study identified variables which influence the outcome of surgical management on 126 ununited scaphoid fractures managed by internal fixation and non-vascular bone grafting. The site of fracture was defined by a new method: the ratio of the length of the proximal fragment to the sum of the lengths of both fragments, calculated using specific views in the plain radiographs. Bone healing occurred in 71% (89) of cases. Only the site of nonunion (p = 1 x 10(-6)) and the delay to surgery (p = 0.001) remained significant on multivariate analysis. The effect of surgical delay on the probability of union increased as the fracture site moved proximally. A prediction model was produced by stepwise logistic regression analysis, enabling the surgeon to predict the success of surgery where the site of the nonunion and delay to surgery is known. PMID:17540748

  17. Photostress Testing Device for Diagnosing Retinal Disease

    Elizabeth Swan


    Full Text Available Retinal diseases such as Age-Related Macular Degeneration (ARMD affect nearly one in three elderly patients. ARMD damages the central vision photoreceptors in the fovea. The Photostress Test is a simple technique for testing for the early effects of ARMD. Here, the illumination sources in a novel self-administered Photostress Testing device were modeled for safety and distribution in illumination software. After satisfying the design constraints in the model, a prototype of the illumination system was fabricated and tested to confirm the modeling results. The resultant prototype can be used to aid in the diagnosis of retinal disease and is well within retinal safety levels.

  18. Multiple extra macular branch retinal vein occlusions in hyperhomocysteinemia

    Abhijit Diwakar Gore


    Full Text Available Hyperhomocysteinemia is a well-known modifiable risk factor for thromboembolism. Retinal vascular occlusion in patients having hyperhomocysteinemia is a known entity, particularly in young patients. However, multiple extra macular branch retinal vein occlusion (BRVO is a rare condition, which can be a presentation of this disease. We present a patient who had multiple extra macular BRVO; on complete systemic workup, he was found to have raised homocysteine levels.

  19. Cytometric analysis of retinopathies in retinal trypsin digests

    Ghanian, Zahra; Staniszewski, Kevin; Sorenson, Christine M.; Sheibani, Nader; Ranji, Mahsa


    The objective of this work was to design an automated image cytometry tool for determination of various retinal vascular parameters including extraction of features that are relevant to postnatal retinal vascular development, and the progression of diabetic retinopathy. To confirm the utility and accuracy of the software, retinal trypsin digest from TSP1-/- and diabetic Akita/+; TSP1-/- mice were analyzed. TSP1 is a critical inhibitor of development of retinopathies and lack of TSP1 exacerbates progression of early diabetic retinopathies. Loss of vascular cells of and gain more acellular capillaries as two major signs of diabetic retinopathies were used to classify a retina as normal or injured. This software allows quantification and high throughput assessment of retinopathy changes associated with diabetes.

  20. The expression and function of vascular endothelial growth factor in retinal pigment epithelial (RPE) cells is regulated by 4-hydroxynonenal (HNE) and glutathione S-transferaseA4-4

    Vatsyayan, Rit; Lelsani, Poorna Chandra Rao; Chaudhary, Pankaj; Kumar, Sushil; Awasthi, Sanjay [Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Awasthi, Yogesh C., E-mail: [Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)


    Highlights: Black-Right-Pointing-Pointer Low concentration of HNE (0.1-1.0 {mu}M) induced secretion of VEGF in RPE cells. Black-Right-Pointing-Pointer VEGF secreted medium of RPE cells promoted proliferation of endothelial cells. Black-Right-Pointing-Pointer VEGFR2 expression was attenuated with increasing concentrations of HNE. Black-Right-Pointing-Pointer These effects of HNE could be blocked by the over expression of GSTA4-4 in cells. -- Abstract: It is well established that 4-hydroxynonenal (HNE) plays a major role in oxidative stress-induced signaling and the toxicity of oxidants. Surprisingly our recent studies also demonstrate that low levels of HNE generated during oxidative stress promote cell survival mechanisms and proliferation. Since the expression and secretion of VEGF is known to be affected by Oxidative stress, during present studies, we have examined dose dependent effect of HNE on VEGF expression and secretion in a model of retinal pigment epithelial (RPE) cells in culture. Results of these studies showed that while inclusion of 0.1 {mu}M HNE in the medium caused increased secretion of VEGF, its secretion and expression was significantly suppressed in the presence of >5 {mu}M HNE in the media. These concentration dependent hormetic effects of HNE on VEGF secretion could be blocked by the over expression of GSTA4-4 indicating that these effects were specifically attributed to HNE and regulated by GSTA4-4. VEGF secreted into the media showed angiogenic properties as indicated by increased migration and tube formation of HUVEC in matrigel when grown in media from RPE cells treated with 1 {mu}M HNE. The corresponding media from GSTA4-4 over expressing RPE cells had no effect on migration and tube formation of HUVEC in matrigel. These results are consistent with earlier studies showing that at low concentrations, HNE promotes proliferative mechanisms and suggest that HNE induces VEGF secretion from RPE cells that acts in a paracrine fashion to induce

  1. Marfan Syndrome Presenting with Bilateral Retinal Detachment

    Subrata Chakrabarti; Koushik Pan


    Marfan syndrome is an autosomal dominant systemic disorder of the connective tissue. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessels. Eye involvement may be in the form of retinal detachment which is a potentially dangerous manifestation for its sight threatening nature .We report a case where a 17 year old male developed sudden blindness due to spontaneous bilateral retinal detachment. Examination revealed features...

  2. Automated measurement of retinal blood vessel tortuosity

    Joshi, Vinayak; Reinhardt, Joseph M.; Abramoff, Michael D.


    Abnormalities in the vascular pattern of the retina are associated with retinal diseases and are also risk factors for systemic diseases, especially cardiovascular diseases. The three-dimensional retinal vascular pattern is mostly formed congenitally, but is then modified over life, in response to aging, vessel wall dystrophies and long term changes in blood flow and pressure. A characteristic of the vascular pattern that is appreciated by clinicians is vascular tortuosity, i.e. how curved or kinked a blood vessel, either vein or artery, appears along its course. We developed a new quantitative metric for vascular tortuosity, based on the vessel's angle of curvature, length of the curved vessel over its chord length (arc to chord ratio), number of curvature sign changes, and combined these into a unidimensional metric, Tortuosity Index (TI). In comparison to other published methods this method can estimate appropriate TI for vessels with constant curvature sign and vessels with equal arc to chord ratios, as well. We applied this method to a dataset of 15 digital fundus images of 8 patients with Facioscapulohumeral muscular dystrophy (FSHD), and to the other publically available dataset of 60 fundus images of normal cases and patients with hypertensive retinopathy, of which the arterial and venous tortuosities have also been graded by masked experts (ophthalmologists). The method produced exactly the same rank-ordered list of vessel tortuosity (TI) values as obtained by averaging the tortuosity grading given by 3 ophthalmologists for FSHD dataset and a list of TI values with high ranking correlation with the ophthalmologist's grading for the other dataset. Our results show that TI has potential to detect and evaluate abnormal retinal vascular structure in early diagnosis and prognosis of retinopathies.

  3. Prevention and treatment of peritoneal adhesions in patients affected by vascular diseases following surgery: a review of the literature

    Rocca Aldo


    Full Text Available Intra-abdominal adhesions are the most frequently occurring postoperative complication following abdomino-pelvic surgery. Abdominal and pelvic surgery can lead to peritoneal adhesion formation causing infertility, chronic pelvic pain, and intestinal obstruction. Laparoscopy today is considered the gold standard of care in the treatment of several abdominal pathologies as well as in a wide range of vascular diseases. Laparoscopy has several advantages in comparison to open surgery. These include rapid recovery times, shorter hospitalisation, reduced postoperative pain, as well as cosmetic benefits. The technological improvements in this particular surgical field along with the development of modern techniques and the acquisition of specific laparoscopic skills have allowed for its wider utilization in operations with fully intracorporeal anastomoses. Postoperative adhesions are caused by aberrant peritoneal healing and are the leading cause of postoperative bowel obstruction. The use of anti-adherence barriers is currently being advocated for their prevention. The outcome of the investigation showed adhesion formation inhibition without direct detrimental effects on anastomotic healing. Poor anasto-motic healing can provoke adhesions even in the presence of anti-adhesion barriers. This review gives a short overview on the current evidence on the pathophysiology and prevention of peritoneal adhesions.

  4. Preferentially affected sites of cerebral arteriosclerosis in vascular dementia of Binswanger type. A study of MRI and MR angiography

    MRI and MR angiography (MRA) were analyzed to evaluate the preferential sites of cerebral arteriosclerosis in 129 normal controls and 27 patients with vascular dementia of Binswanger type (BVD; mean age 75.0 years). Small vessel disease, indicated as advanced high intensity areas on T2-weighted MRI, increased with advancing age, while large vessel sclerosis detected with MRA did not increase after the age of 80 years. Large vessel sclerosis was not always accompanied with advanced high intensity areas. Large vessel sclerosis was found in 12 (44.4%) of 27 patients with BVD, and was as common as that of the controls of the eighth decade. Large vessel sclerosis was frequently seen in the cases suffering from BVD below 70 years of age or with hypertension. In conclusion, patients with BVD develop cerebral arteriosclerosis more preferentially in the small vessels rather than the large vessels especially in aged cases, of which incidence is similar to that of the normal controls over 80 years of age. (author)

  5. Profound retinal ischaemia after ranibizumab administration in an eye with ocular ischaemic syndrome

    Kofoed, Peter Kristian; Munch, Inger Christine; Larsen, Michael


    Abstract. Purpose: To report the result of ranibizumab administration in an eye with ocular ischaemic syndrome. Methods: Fluorescein angiography, ocular pneumoplethysmography and retinal vessel calibre measurement. Results: An 85-year-old man with ocular ischaemic syndrome demonstrated vision loss......, retinal vessel calibre constriction and profound retinal ischaemia after intravitreal ranibizumab. Conclusion: We advise against the use of intravitreal vascular endothelial growth factor inhibitors in eyes with ocular ischaemic syndrome....

  6. A Partial Intensity Invariant Feature Descriptor for Multimodal Retinal Image Registration

    Chen, Jian; Tian, Jie; Lee, Noah; Zheng, Jian; Smith, R. Theodore; Laine, Andrew F


    Detection of vascular bifurcations is a challenging task in multimodal retinal image registration. Existing algorithms based on bifurcations usually fail in correctly aligning poor quality retinal image pairs. To solve this problem, we propose a novel highly distinctive local feature descriptor named partial intensity invariant feature descriptor (PIIFD) and describe a robust automatic retinal image registration framework named Harris-PIIFD. PIIFD is invariant to image rotation, partially inv...

  7. Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.

    Ismail S Zaitoun

    Full Text Available Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/- are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox and VE-cadherin-cre (Bcl-2EC mice. Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium.

  8. Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.

    Zaitoun, Ismail S; Johnson, Ryan P; Jamali, Nasim; Almomani, Reem; Wang, Shoujian; Sheibani, Nader; Sorenson, Christine M


    Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/-) are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox) and VE-cadherin-cre (Bcl-2EC mice). Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium. PMID:26444547

  9. Changes in vascular and transpiration flows affect the seasonal and daily growth of kiwifruit (Actinidia deliciosa) berry

    Morandi, Brunella; Manfrini, Luigi; Losciale, Pasquale; Zibordi, Marco; Corelli Grappadelli, Luca


    Background and Aims The kiwifruit berry is characterized by an early stage of rapid growth, followed by a relatively long stage of slow increase in size. Vascular and transpiration flows are the main processes through which water and carbon enter/exit the fruit, determining the daily and seasonal changes in fruit size. This work investigates the biophysical mechanisms underpinning the change in fruit growth rate during the season. Methods The daily patterns of phloem, xylem and transpiration in/outflows have been determined at several stages of kiwifruit development, during two seasons. The different flows were quantified by comparing the diurnal patterns of diameter change of fruit, which were then girdled and subsequently detached while measurements continued. The diurnal courses of leaf and stem water potential and of fruit pressure potential were also monitored at different times during the season. Key Results Xylem and transpiration flows were high during the first period of rapid volume growth and sharply decreased with fruit development. Specific phloem import was lower and gradually decreased during the season, whereas it remained constant at whole-fruit level, in accordance with fruit dry matter gain. On a daily basis, transpiration always responded to vapour pressure deficit and contributed to the daily reduction of fruit hydrostatic pressure. Xylem flow was positively related to stem-to-fruit pressure potential gradient during the first but not the last part of the season, when xylem conductivity appeared to be reduced. Conclusions The fruit growth model adopted by this species changes during the season due to anatomical modifications in the fruit features. PMID:20382641

  10. Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.

    Thomas A Mendel

    Full Text Available BACKGROUND: Retinal vasculopathies, including diabetic retinopathy (DR, threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. METHODOLOGY/PRINCIPAL FINDINGS: We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR, ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area. ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction. Treatment of ASCs with transforming growth factor beta (TGF-β1 enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection. CONCLUSIONS/SIGNIFICANCE: ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple

  11. Automatic classification of retinal vessels into arteries and veins

    Niemeijer, Meindert; van Ginneken, Bram; Abràmoff, Michael D.


    Separating the retinal vascular tree into arteries and veins is important for quantifying vessel changes that preferentially affect either the veins or the arteries. For example the ratio of arterial to venous diameter, the retinal a/v ratio, is well established to be predictive of stroke and other cardiovascular events in adults, as well as the staging of retinopathy of prematurity in premature infants. This work presents a supervised, automatic method that can determine whether a vessel is an artery or a vein based on intensity and derivative information. After thinning of the vessel segmentation, vessel crossing and bifurcation points are removed leaving a set of vessel segments containing centerline pixels. A set of features is extracted from each centerline pixel and using these each is assigned a soft label indicating the likelihood that it is part of a vein. As all centerline pixels in a connected segment should be the same type we average the soft labels and assign this average label to each centerline pixel in the segment. We train and test the algorithm using the data (40 color fundus photographs) from the DRIVE database1 with an enhanced reference standard. In the enhanced reference standard a fellowship trained retinal specialist (MDA) labeled all vessels for which it was possible to visually determine whether it was a vein or an artery. After applying the proposed method to the 20 images of the DRIVE test set we obtained an area under the receiver operator characteristic (ROC) curve of 0.88 for correctly assigning centerline pixels to either the vein or artery classes.

  12. Consumption of Polyphenol-Rich Zingiber Zerumbet Rhizome Extracts Protects against the Breakdown of the Blood-Retinal Barrier and Retinal Inflammation Induced by Diabetes

    Thing-Fong Tzeng


    Full Text Available The present study investigates the amelioration of diabetic retinopathy (DR by Zingiber zerumbet rhizome ethanol extracts (ZZRext in streptozotocin-induced diabetic rats (STZ-diabetic rats. ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day for three months. Blood-retinal barrier (BRB breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL-1β, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.

  13. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu


    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  14. Macrovaso retiniano congênito: relato de caso Congenital retinal macrovessel: case report

    Rodrigo Tavares Schueler


    Full Text Available O macrovaso retiniano congênito é rara anomalia vascular em que um vaso grande e suas tributárias cruzam a mácula. Descrevemos um caso de macrovaso retiniano em paciente com queixa de baixa acuidade visual.Congenital retinal macrovessel is a rare vascular anomaly in which a large vessel and its tributaries cross the macula. We describe a case of retinal macrovessel in a patient complaining of decrease in visual acuity.

  15. Prepapillary Vascular Loops Complicated by Suspected Macroaneurysm Rupture

    Kei Akaiwa


    Full Text Available We present a case of prepapillary vascular loops complicated by a suspected macroaneurysm rupture which was treated with intravitreal bevacizumab (IVB. A 62-year-old woman presented with decreased vision and myodesopsia in her left eye. Her best-corrected visual acuity (BCVA was 0.6 in the left eye. Fundus examination disclosed an elevated, round, and reddish lesion, retinal hemorrhage at the superior aspect of the optic disc, retinal opacification along the superior branch retinal artery, and a small vitreous hemorrhage. Optical coherence tomography showed a serous retinal detachment, and indocyanine green angiography demonstrated prepapillary vascular loops and a hypofluorescent area with hyperfluorescent margins. These findings suggested the presence of a macroaneurysm. No filling of the dye in the aneurysm-like dilatation suggested a blockage of the lumen with a thrombus which might be associated with a branch retinal artery occlusion (BRAO. A diagnosis of prepapillary vascular loops complicated by a suspected macroaneurysm rupture and BRAO was made. Because of a persistent serous retinal detachment, IVB was performed. One month later, the BCVA improved to 1.0. Fundus examination disclosed an organized yellowish-white macroaneurysm and resolution of the serous retinal detachment. We recommend careful monitoring of patients with prepapillary vascular loops because of complications such as macroaneurysm rupture and BRAO.

  16. 孕期酒精暴露对子鼠视网膜双极细胞和水平细胞发育的影响%Prenatal alcohol exposure affects development of retinal bipolar and horizontal cells in mice

    刘曦; 王永毅; 姚焕玲; 赵博; 于亚东; 胡馨; 邓锦波


    Objective To investigate effects of alcohol exposure during pregnancy on retinal bipolar and horizontal cells in filial mice. Methods The animal model of prenatal alcohol exposure was made. The development of bipolar cells and horizontal cells at prenatal days 7, 14 and 30 was investigated with immunofluorescent labeling and Dil scattering techniques. Results In all age groups, the density of the bipolar cells was significantly lower in the experiment groups than in the control groups. The dendritic field and the number of branches of horizontal cells were significantly lower in the experimental group than in the control group (P < 0. 01). Conclusion Alcohol exposure during pregnancy affects development of retinal bipolar and horizontal cells in mice.%目的 探讨孕期酒精暴露对子鼠视网膜双极细胞和水平细胞发育的影响.方法 建立孕期酒精暴露小鼠模型;采用免疫荧光染色和DiI散射技术,观察酒精对日龄7d(P7)、P14和P30子鼠视网膜双极细胞和水平细胞的影响.结果 各年龄组中,酒精组视网膜双极细胞的密度明显低于对照组,且呈剂量依赖性和长时程效应;水平细胞的树突野及树突数也明显低于对照组,呈剂量依赖性和长时程效应(P<0.01).结论 孕期酒精暴露影响子鼠视网膜双极细胞和水平细胞的发育.

  17. Modern retinal laser therapy

    Kozak, Igor; Luttrull, Jeffrey K.


    Medicinal lasers are a standard source of light to produce retinal tissue photocoagulation to treat retinovascular disease. The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study were large randomized clinical trials that have shown beneficial effect of retinal laser photocoagulation in diabetic retinopathy and have dictated the standard of care for decades. However, current treatment protocols undergo modifications. Types of lasers used in treatment of retinal dise...

  18. Thrombolysis in vascular surgery

    Smith, Linn


    Background and aims: Thrombolysis is in common use in the treatment of acute forms of vascular disease. It may be used both systemically and locally, in the latter case through an endovascular approach, socalled catheter-directed thrombolysis. The aims of this thesis were to investigate how thrombolysis affects performance-related outcomes pertaining to vascular patency after thrombolysis, and how it affects patient safety and the development of complications. Metho...

  19. The retinal ciliopathies.

    Adams, N A; Awadein, Ahmed; Toma, Hassanain S


    While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present. PMID:17896309

  20. Overexpression of retinal degeneration slow (RDS protein adversely affects rods in the rd7 model of enhanced S-cone syndrome.

    Dibyendu Chakraborty

    Full Text Available The nuclear receptor NR2E3 promotes expression of rod photoreceptor genes while repressing cone genes. Mice lacking NR2E3 (Nr2e3(rd7/rd7 referred to here as rd7 are a model for enhanced S-cone syndrome, a disease associated with increased sensitivity to blue light and night blindness. Rd7 retinas have reduced levels of the outer segment (OS structural protein retinal degeneration slow (RDS. We test the hypothesis that increasing RDS levels would improve the Rd7 phenotype. Transgenic mice over-expressing normal mouse peripherin/RDS (NMP in rods and cones were crossed onto the rd7 background. Disease phenotypes were assessed in NMP/rd7 eyes and compared to wild-type (WT and rd7 eyes at postnatal day 30. NMP/rd7 retinas expressed total RDS (transgenic and endogenous message at WT levels, and NMP protein was correctly localized to the OS. NMP/rd7 retinas have shorter OSs compared to rd7 and WT and significantly reduced number of rosettes. NMP/rd7 mice also exhibited significant deficits in scotopic ERG amplitudes compared to rd7 while photopic amplitudes remained unaffected. Protein levels of rhodopsin, RDS, and the RDS homologue ROM-1 were significantly reduced in the NMP/rd7 retinas compared to rd7. We show that correcting the levels of RDS gene expression does not improve the phenotype of the rd7 suggesting that RDS deficiency is not responsible for the defect in this model. We suggest that the specific rod defect in the NMP/rd7 is likely associated with ongoing problems in the rd7 that are related to the expression of cone genes in rod cells, a characteristic of the model.

  1. Myocardial performance index is sensitive to changes in cardiac contractility, but is also affected by vascular load condition.

    Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Shishido, Toshiaki; Sugimachi, Masaru


    Myocardial performance index (MPI), or Tei index, is measured by Doppler echocardiography in clinical practice. MPI has been shown to be useful in evaluating left ventricular (LV) performance and predicting prognosis in cardiac patients. However, the effects of LV load and contractile states on MPI remain to be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure-volume relationship with use of sonomicrometry and catheter-tip manometry. MPI was determined from the time derivative of LV volume and pressure. LV end-systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV end-diastolic volume (Ved) were used as indices of LV contractility, afterload and preload, respectively. Hemodynamic conditions were varied over wide ranges [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing cardiovascular agents, by inducing ischemic heart failure and by electrical atrial pacing. Multiple linear regression analysis of pooled data (66 data sets) indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg · ml(-1), pVed (11-100 ml, p0.1). Theoretical analysis also indicated that MPI decreases following the increases in LV contractility and in preload, while it increases in response to an increase in LV afterload. We conclude that MPI sensitively detects changes in LV contractility. However, MPI is also affected by changes in LV afterload and preload. PMID:24109782

  2. Arginase 2 deficiency reduces hyperoxia-mediated retinal neurodegeneration through the regulation of polyamine metabolism.

    Narayanan, S P; Xu, Z; Putluri, N; Sreekumar, A; Lemtalsi, T; Caldwell, R W; Caldwell, R B


    Hyperoxia treatment has been known to induce neuronal and glial death in the developing central nervous system. Retinopathy of prematurity (ROP) is a devastating disease in premature infants and a major cause of childhood vision impairment. Studies indicate that, in addition to vascular injury, retinal neurons are also affected in ROP. Using an oxygen-induced retinopathy (OIR) mouse model for ROP, we have previously shown that deletion of the arginase 2 (A2) significantly reduced neuro-glial injury and improved retinal function. In the current study, we investigated the mechanism of A2 deficiency-mediated neuroprotection in the OIR retina. Hyperoxia treatment has been known to induce neuronal death in neonates. During the hyperoxia phase of OIR, a significant increase in the number of apoptotic cells was observed in the wild-type (WT) OIR retina compared with A2-deficient OIR. Mass spectrometric analysis showed alterations in polyamine metabolism in WT OIR retina. Further, increased expression level of spermine oxidase was observed in WT OIR retina, suggesting increased oxidation of polyamines in OIR retina. These changes were minimal in A2-deficient OIR retina. Treatment using the polyamine oxidase inhibitor, N, N'-bis (2, 3-butadienyl)-1, 4-butanediamine dihydrochloride, significantly improved neuronal survival during OIR treatment. Our data suggest that retinal arginase is involved in the hyperoxia-induced neuronal degeneration in the OIR model, through the regulation of polyamine metabolism. PMID:24556690

  3. Possibility of enhanced risk of retinal neovascularization in repeated blood donors: blood donation and retinal alteration

    Rastmanesh R


    Full Text Available Reza RastmaneshDepartment of Clinical Nutrition and Dietetics, Shahid Beheshti University of Medical Sciences, National Nutrition and Food Technology Research Institute, Tehran, IranAbstract: Repeated blood donors manifest clinical, subclinical, and biochemical signs of iron deficiency anemia, have significantly higher erythropoietin and vascular endothelial growth factor (VEGF concentrations, and decreased tissue oxygen saturation, oxygenated tissue hemoglobin, and regional cerebral oxygen saturation. Erythropoietin and VEGF are potent retinal angiogenic factors which may initiate and promote the retinal angiogenesis process independently or simultaneously. Increases in circulating levels of erythropoietin and VEGF are proportionate to the levels of hematocrit, hypoxemia, and tissue hypoxia. It is suggested that higher erythropoietin production following iron deficiency anemia-induced chronic hypoxemia/hypoxia may, hypothetically, enhance the risk of retinal angiogenesis and/or neovascularization, possibly by inducing hypoxia inducible factor-1 alpha, which consequently upregulates genes stimulating angiogenesis, resulting in formation of a new vasculature, possibly by modulation of signal transducer and activator of transcription 3 signaling in the retina. Implications of this hypothesis cover erythropoietin doping, chronic hypoxia, and hypoxemic situations, such as angiogenesis-related cardiac and pulmonary diseases.Keywords: repeated blood donation, erythropoietin, retinal neovascularization, vascular endothelial growth factor, hypoxia

  4. Functional and structural modifications during retinal degeneration in the rd10 mouse

    Barhoum, Rima; Martínez Navarrete, Gema Concepción; Corrochano Sánchez, Silvia; Germain Martínez, Francisco; Fernández Sánchez, Laura; Rosa Cano, Enrique J. de la; Villa Polo, Pedro de la; Cuenca Navarro, Nicolás


    Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have studied degener- ation in the rd10 mice both by immunocytochemistry and TUNEL-labeling of retinal cells, and through electrophysiological recordings. The cell degeneration in the retina of rd10 mice produced appreciable morphological changes in rod and cone cells by P20. Retinal cell death is clearly observed in the central retina and it peaked...

  5. Human identification system based on the detection of optical Disc Ring in retinal images

    Chihaoui, Takwa; Kachouri, Rostom; Jlassi, Hejer; Akil, Mohamed; Hamrouni, Kamel


    Retinal identification is being studied as a hot research topic in the biometric field. Many factors such as the poor quality of retinal images and the huge execution time can seriously affect the performance of the retinal identification systems. In this context, in order to compromise the quality and the processing time, this paper presents a human identification system based on a new preprocessing method of retinal images that we call optical Disc Ring detection method. The proposed ODR me...

  6. Compliance of the aorta in two diseases affecting vascular elasticity, familial hypercholesterolemia and diabetes: a MRI study

    Sami Soljanlahti


    Full Text Available Sami Soljanlahti1, Taina Autti1, Laura Hyttinen2, Alpo F Vuorio3, Pekka Keto1, Kirsi Lauerma11Helsinki Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland; 2Department of Internal Medicine, North Karelia Central Hospital, Joensuu, Finland; 3Division of Internal Medicine, Department of Medicine, University of Helsinki, Helsinki, FinlandAbstract: Arterial elasticity changes in familial hypercholesterolemia (FH and diabetes mellitus (DM with different but overlapping mechanisms. We compared aortic elasticity between 19 FH patients with the same mutation, 18 type 2 DM patients, and 30 controls, all aged 48 to 64. They underwent aortic magnetic resonance imaging, risk-factor assessment, and carotid and femoral ultrasound measurements. All patients were on adequate cardiovascular medication including statins and had established coronary heart disease (CHD. FH patients had longer-duration CHD (13.3 ± 7.7 years than did DM patients (5.0 ± 3.1. Aortic compliance in the descending thoracic (DM 0.38 ± 0.14 vs control 0.53 ± 0.19, P = 0.032 and abdominal aorta (DM 0.45 ± 0.20 vs control 0.66 ± 0.25, P = 0.011 was lower in DM patients than in controls, whereas no significant difference existed between FH patients and controls. Carotid and femoral intima-media thickness was greater in FH and DM patients than in controls with no difference between patient groups. Carotid or femoral plaques appeared in 15 (79% FH and in 10 (56% DM patients. One control had a femoral plaque. Five FH patients showed stenosis, occlusion or both in carotid arteries. In our opinion, DM patients’ lower compliance reflect mainly arterial media affecting arteriosclerosis, while FH patients’ plaque status and longer duration of CHD suggest more advanced atherosclerosis. The FH patients may therefore be at increased risk for atherothrombotic events. However, due to small patient material, larger confirmatory studies are needed.Keywords: MRI

  7. Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies.

    Welikala, R A; Fraz, M M; Foster, P J; Whincup, P H; Rudnicka, A R; Owen, C G; Strachan, D P; Barman, S A


    Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost. PMID:26894596

  8. Wide-field optical coherence tomography based microangiography for retinal imaging

    Zhang, Qinqin; Lee, Cecilia S.; Chao, Jennifer; Chen, Chieh-Li; Zhang, Thomas; Sharma, Utkarsh; Zhang, Anqi; Liu, Jin; Rezaei, Kasra; Pepple, Kathryn L.; Munsen, Richard; Kinyoun, James; Johnstone, Murray; van Gelder, Russell N.; Wang, Ruikang K.


    Optical coherence tomography angiography (OCTA) allows for the evaluation of functional retinal vascular networks without a need for contrast dyes. For sophisticated monitoring and diagnosis of retinal diseases, OCTA capable of providing wide-field and high definition images of retinal vasculature in a single image is desirable. We report OCTA with motion tracking through an auxiliary real-time line scan ophthalmoscope that is clinically feasible to image functional retinal vasculature in patients, with a coverage of more than 60 degrees of retina while still maintaining high definition and resolution. We demonstrate six illustrative cases with unprecedented details of vascular involvement in retinal diseases. In each case, OCTA yields images of the normal and diseased microvasculature at all levels of the retina, with higher resolution than observed with fluorescein angiography. Wide-field OCTA technology will be an important next step in augmenting the utility of OCT technology in clinical practice.

  9. A Case of Retinal Tear Associated with Use of Sorafenib

    KellyM.Gaertner; OsamaRahma; StephenH.Caldwell


    Inhibition of angiogenesis is a target in the treatment of a variety of malignancies. Sorafenib is an oral inhibitor of multiple tyrosine kinases involved in tumor angiogenesis. A related case of ophthalmologic toxicity has been reported with another vascular endothelial growth factor receptor inhibitor, sunitinib. We report the first case of retinal tear possibly associated with sorafenib.

  10. Heritability of retinal vessel diameters and blood pressure

    Taarnhøj, Nina C B B; Larsen, Michael; Sander, Birgit;


    , aged 20 to 46 years, interpolated diameter estimates for the central retinal artery (CRAE), the central retinal vein (CRVE), and the artery-to-vein diameter ratio (AVR) were assessed by analysis of digital gray-scale fundus photographs of right eyes. RESULTS: The heritability was 70% (95% CI: 54...... for CRVE, and 0.67 +/- 0.05 microm for AVR. No significant influence on artery or vein diameters was found for gender, smoking, body mass index (BMI), total cholesterol, fasting blood glucose, or 2-hour oral glucose tolerance test values. CONCLUSIONS: In healthy young adults with normal blood pressure...... and blood glucose, variations in retinal blood vessel diameters and blood pressure were predominantly attributable to genetic effects. A genetic influence may have a role in individual susceptibility to hypertension and other vascular diseases. The results suggest that retinal vessel diameters and the...

  11. Orthogonal moments for determining correspondence between vessel bifurcations for retinal image registration.

    Patankar, Sanika S; Kulkarni, Jayant V


    Retinal image registration is a necessary step in diagnosis and monitoring of Diabetes Retinopathy (DR), which is one of the leading causes of blindness. Long term diabetes affects the retinal blood vessels and capillaries eventually causing blindness. This progressive damage to retina and subsequent blindness can be prevented by periodic retinal screening. The extent of damage caused by DR can be assessed by comparing retinal images captured during periodic retinal screenings. During image acquisition at the time of periodic screenings translation, rotation and scale (TRS) are introduced in the retinal images. Therefore retinal image registration is an essential step in automated system for screening, diagnosis, treatment and evaluation of DR. This paper presents an algorithm for registration of retinal images using orthogonal moment invariants as features for determining the correspondence between the dominant points (vessel bifurcations) in the reference and test retinal images. As orthogonal moments are invariant to TRS; moment invariants features around a vessel bifurcation are unaltered due to TRS and can be used to determine the correspondence between reference and test retinal images. The vessel bifurcation points are located in segmented, thinned (mono pixel vessel width) retinal images and labeled in corresponding grayscale retinal images. The correspondence between vessel bifurcations in reference and test retinal image is established based on moment invariants features. Further the TRS in test retinal image with respect to reference retinal image is estimated using similarity transformation. The test retinal image is aligned with reference retinal image using the estimated registration parameters. The accuracy of registration is evaluated in terms of mean error and standard deviation of the labeled vessel bifurcation points in the aligned images. The experimentation is carried out on DRIVE database, STARE database, VARIA database and database provided

  12. Metabolic syndrome and central retinal artery occlusion

    Kosanović-Jaković Natalija


    Full Text Available Background. The accumulation of risk factors for central retinal artery occlusion can be seen in a single person and might be explained by the metabolic syndrome. Case report. We presented the case of a 52-year-old man with no light perception in his right eye. The visual loss was monocular and painless, fundoscopy showed central retinal artery occlusion and the laboratory investigation showed the raised erythrocyte sedimentation rate of 105 mm/h and the raised C-reactive protein of 22 mg/l. Specific laboratory investigations and fluorescein angiography excluded the presence of vasculitis, collagen vascular diseases, hypercoagulable state and antiphospholipid syndrome. Conclusion. The patient met all the five of the National Cholesterol Education Program (NCEP criteria for the metabolic syndrome: hypertension, abnormal lipid profile, abnormal glucose metabolism, obesity and hyperuricemia. Measurement of C-reactive protein is useful for the assessment of therapeutic systemic effect on any abnormality in the metabolic syndrome. Individual therapy for all risk factors in the metabolic syndrome is necessary to prevent complications such as cardiovascular, retinal vascular diseases and stroke.

  13. A case of CRB1-negative Coats-like retinitis pigmentosa.

    Sarao, Valentina; Veritti, Daniele; Prosperi, Raffaele; Pignatto, Silvia; Lanzetta, Paolo


    Retinitis pigmentosa is a heterogeneous group of ocular diseases that causes progressive degeneration of the photoreceptor cells mainly affecting the rods of the peripheral retina. The association between retinitis pigmentosa and exudative retinopathy was first described in 1956 and has been called "Coats-like retinitis pigmentosa." Mutations in the Crumbs homolog 1 (CRB1) gene have been reported as a risk factor for developing Coats-like changes in patients with autosomal recessive retinitis pigmentosa. We report the case of a 15-year-old girl affected by CRB1 gene-negative retinitis pigmentosa and Coats-like exudative vasculopathy who was successfully treated with laser photocoagulation. PMID:23871396

  14. Laser photocoagulation for retinal vein occlusion

    K. A. Mirzabekova


    Full Text Available Retinal vein occlusion (RVO is one of the leading causes of permanent vision loss. In adults, central retinal vein occlusion (CRVO occurs in 1.8% while branch retinal vein occlusion (BRVO occurs in 0.2%. Treatment strategy and disease prognosis are determined by RVO type (ischemic/non-ischemic. Despite numerous studies and many current CRVO and BRVO treatment approaches, the management of these patients is still being debated. Intravitreal injections of steroids (triamcinolone acetate, dexamethasone and vascular endothelial growth factor (VEGF inhibitors (bevacizumab, ranibizumab were shown to be fairly effective. However, it is unclear whether anti-VEGF agents are reasonable in ischemic RVOs. Laser photocoagulation remains the only effective treatment of optic nerve head and/or retinal neovascularization. Laser photocoagulation is also indicated for the treatment of macular edema. Both threshold and sub-threshold photocoagulation may be performed. Photocoagulation performed with argon (514 nm, krypton (647 nm, or diode (810 nm laser for macular edema provides similar results (no significant differences. The treatment may be complex and include medication therapy and/or surgery. Medication therapy includes anti-aggregant agents and antioxidants, i.e., emoxypine which may be used in acute RVO as well as in post-thrombotic retinopathy. 

  15. Repetitive magnetic stimulation improves retinal function in a rat model of retinal dystrophy

    Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael


    Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.

  16. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

    Villegas VM


    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  17. Risk Factors for Central and Branch Retinal Vein Occlusion: A Meta-Analysis of Published Clinical Data

    Kolar, Petr


    Retinal vein occlusion (RVO) is a major cause of vision loss. Of the two main types of RVO, branch retinal vein occlusion (BRVO) is 4 to 6 times more prevalent than central retinal vein occlusion (CRVO). A basic risk factor for RVO is advancing age. Further risk factors include systemic conditions like hypertension, arteriosclerosis, diabetes mellitus, hyperlipidemia, vascular cerebral stroke, blood hyperviscosity, and thrombophilia. A strong risk factor for RVO is the metabolic syndrome (hyp...

  18. Changes in retinal vessels related to varicocele: a pilot investigation.

    Coşkun, M; Ilhan, N; Elbeyli, A; Rifaioğlu, M M; Inci, M; Davran, R; Tuzcu, E A; Yarbağ, A; Davarci, M; Gökçe, A


    The aim of this study was to investigate whether retinal vasculature changes had occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio) in patients with varicocele. This pilot study included 50 healthy subjects with any eye disease apart from slight refractive errors and 55 patients with varicocele. Retinal arteriolar and venular diameters were measured and summarised as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Retinal microvascular diameters and the arteriolar-to-venular ratio (AVR) were assessed with a digital retinal camera. All measurements and calculations were performed using a computer-based program. The mean CRAE value was 151.8 ± 3.6 μm in the study group and 150.4 ± 4.5 μm in the control group. Mean CRVE value was 209.4 ± 5.9 μm in the study group and 200.1 ± 8.7 μm in the control group. AVR was found 0.72 ± 0.02 in the study group and 0.75 ± 0.03 in the control group. There were significant differences between groups in terms of CRVE and AVR. There were no significant differences between groups in terms of CRAE. The results of this study showed that the patients with varicocele showed significant changes on retinal vascular diameter. PMID:26314401

  19. Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits

    de Hoz, Rosa; Salazar, Juan J; Ramírez, Ana I; Rojas, Blanca; Gallego, Beatriz I.; Triviño, Alberto; Tejerina, Teresa


    To evaluate the pleiotropic effects to statins, we analyze the qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment. For this purpose, New Zealand rabbits were split into three groups: control (G0; n = 10), fed a standard diet; hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months; and statins (G2; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months, together with the administration of statin (pravastatin or fluvastatin sodium) at a dose of 2 mg / kg / day each diet. The retinas were analyzed by transmission electron microscopy and immunohistochemistry (glial fibrillary acidic protein). The retinal thickness of nuclear and plexiform layers were quantified in semi-thin sections. The results revealed that the low-statin-treated rabbits in comparison with the hypercholesterolemic group showed: i) a more preserved structure in all retinal layers; ii) a significant reduction in retinal thickness; iii) a decrease in cell death in the nuclear-and ganglion-cell layers; iv) a reduction of hydropic degeneration in the plexiform and nerve-fiber layers; v) a preservation of astrocytes and of the retinal area occupied by them; and vi) a better-preserved retinal vascular structure. Our findings indicate that low doses of statins can prevent retinal degeneration, acting on retinal macroglia, neurons and retinal vessels, despite that hypercholesterolemia remained unchanged. Thus, the pleiotropic effects of the statins may help safeguard the retinal ultrastructure. PMID:27144842

  20. Activation tagging of the two closely linked genes LEP and VAS independently affects vascular cell number

    van der Graaff, Eric; Hooykaas, Paul J J; Keller, Beat


    report that in addition to this leafy petiole phenotype, the size of the vascular bundles is increased in all aerial organs in let as a result of an increase in the number of xylem, phloem (pro)cambial and pericycle cells. This vascular phenotype is caused by activation tagging of the two genes VASCULAR......-promoting factor. The activation tagging of VAS only resulted in a specific increase in phloem (pro)cambial and pericycle cells. We conclude that activation tagging of LEP and VAS results in additive phenotypes. Insertional mutants for LEP and VAS display wild-type vascular development, indicating the relevance of...... activation tagging for functional analysis of novel genes involved in plant development....

  1. [Acute retinal necrosis].

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H


    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  2. Retinal laser optical aids

    Das Traprasad


    Full Text Available Knowledge of optics, comparative magnification and working field of view is essential for rational use of ophthalmoscopic contact lenses for retinal photocoagulation. The three commonly used contact lenses are described and compared.

  3. Retinal Tears and Detachments

    ... does not cause retinal damage. However, inflammation or myopia (nearsightedness) may cause the vitreous to pull away ... repaired? If your retina is only torn, prompt treatment may prevent detachment. Your eye surgeon will discuss ...

  4. Advances in retinal ganglion cell imaging.

    Balendra, S I; Normando, E M; Bloom, P A; Cordeiro, M F


    Glaucoma is one of the leading causes of blindness worldwide and will affect 79.6 million people worldwide by 2020. It is caused by the progressive loss of retinal ganglion cells (RGCs), predominantly via apoptosis, within the retinal nerve fibre layer and the corresponding loss of axons of the optic nerve head. One of its most devastating features is its late diagnosis and the resulting irreversible visual loss that is often predictable. Current diagnostic tools require significant RGC or functional visual field loss before the threshold for detection of glaucoma may be reached. To propel the efficacy of therapeutics in glaucoma, an earlier diagnostic tool is required. Recent advances in retinal imaging, including optical coherence tomography, confocal scanning laser ophthalmoscopy, and adaptive optics, have propelled both glaucoma research and clinical diagnostics and therapeutics. However, an ideal imaging technique to diagnose and monitor glaucoma would image RGCs non-invasively with high specificity and sensitivity in vivo. It may confirm the presence of healthy RGCs, such as in transgenic models or retrograde labelling, or detect subtle changes in the number of unhealthy or apoptotic RGCs, such as detection of apoptosing retinal cells (DARC). Although many of these advances have not yet been introduced to the clinical arena, their successes in animal studies are enthralling. This review will illustrate the challenges of imaging RGCs, the main retinal imaging modalities, the in vivo techniques to augment these as specific RGC-imaging tools and their potential for translation to the glaucoma clinic. PMID:26293138

  5. Marfan Syndrome Presenting with Bilateral Retinal Detachment

    Subrata Chakrabarti


    Full Text Available Marfan syndrome is an autosomal dominant systemic disorder of the connective tissue. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessels. Eye involvement may be in the form of retinal detachment which is a potentially dangerous manifestation for its sight threatening nature .We report a case where a 17 year old male developed sudden blindness due to spontaneous bilateral retinal detachment. Examination revealed features of Marfan syndrome and was stamped as a case of Marfan syndrome by Ghent criteria . The point to stress upon is that a young male developing spontaneous retinal detachment, a diagnosis of underlying Marfan syndrome should be kept in mind if appropriate clinical stigmata are present. [Natl J Med Res 2014; 4(1.000: 104-105

  6. [Muscular Dystrophies Involving the Retinal Function].

    Jägle, H


    Muscular dystrophies are rare disorders, with an incidence of approx. 20 in 100 000. Some dystrophies also affect retinal or optic nerve function. In such cases, the ophthalmological findings may be critical for differential diagnosis or patient counseling. For example in Duchenne muscular dystrophy, where the alteration in retinal function seems to reflect cerebral involvement. Other important forms are mitochondrial and metabolic disorders, such as the Kearns-Sayre syndrome and the Refsum syndrome. Molecular genetic analysis has become a major tool for differential diagnosis, but may be complex and demanding. This article gives an overview of major muscular dystrophies involving retinal function and their genetic origin, in order to guide differential diagnosis. PMID:27011029

  7. Intraocular retinal prosthesis.

    Humayun, M. S.


    PURPOSE: An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can gene...

  8. Vascular quality of care pilot study: how admission to a vascular surgery service affects evidence-based pharmacologic risk factor modification in patients with lower extremity peripheral arterial disease

    Steenhof N


    Full Text Available Naomi Steenhof,1,2 Francesca Le Piane,1 Kori Leblanc,1–3 Naomi R Eisenberg,4 Yvonne Kwan,1 Christine Malmberg,1,6 Alexandra Papadopoulos,5,7 Graham Roche-Nagle4,7,8 1Department of Pharmacy, University Health Network, 2Leslie Dan Faculty of Pharmacy, University of Toronto, 3Centre for Innovation in Complex Care, University Health Network, 4Division of Vascular Surgery, University Health Network, 5Faculty of Nursing, University of Toronto, Toronto, ON, 6Victoria General Hospital, Vancouver Island Health Authority, Victoria, BC, 7Peter Munk Cardiac Centre, University Health Network, 8Faculty of Medicine, University of Toronto, Toronto, ON, Canada Background: Peripheral arterial disease (PAD guidelines recommend aggressive risk factor modification to improve cardiovascular outcomes. Recommended pharmacologic therapies include antiplatelets, angiotensin converting enzyme (ACE inhibitors, and HMG-CoA-reductase inhibitors (statins. Purpose: We studied the degree to which patient admission to a vascular surgery service increased the use of these therapies. Patients and methods: The authors conducted a retrospective chart review of 150 patients with PAD admitted to the vascular surgery service at a large Canadian tertiary care hospital. The use of recommended pharmacologic therapies at the time of admission and discharge were compared. A multidisciplinary clinical team established criteria by which patients were deemed ineligible to receive any of the recommended therapies. Angiotensin receptor blockers (ARBs were considered an alternative to ACE inhibitors. Results: Prior to hospital admission, 64% of patients were on antiplatelet therapy, 67% were on an ACE inhibitor or ARB, and 71% were on a statin. At the time of discharge, 91% of patients were on an antiplatelet (or not, with an acceptable reason, 77% were on an ACE inhibitor or an ARB (or not, with an acceptable reason, and 85% were on a statin (or not, with an acceptable reason. While new

  9. Retinal Remodeling: Concerns, Emerging Remedies, and Future Prospects

    Vidhyasankar eKrishnamoorthy


    Full Text Available Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Müller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs, the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed retinal remodeling, pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies.

  10. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep


    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. PMID:27511757

  11. Branch Retinal Vein Occlusion and Its Management

    Desmond; Archer


    The natural course of Branch Retinal Vein Occlusion is determined by the site and completeness of the occlusion, the integrity of arterial perfusion to the affected sector and the efficiency of the developing collateral circulation. Most patients with tributary vein occlusion have some capillary fall out and microvascular incompetence in the distribution of the affected retina and vision is significantly compromised in over 50% of patients who have either chronic macular oedema or ischemia involving the...

  12. The effects of Δ9-Tetrahydrocannabinole treatment on gonadal micro-vascularization and affected fertility examined by SEM and 3D-morphometry

    Erlbacher, K. M. T.; Minnich, B.


    The present study focuses on the effects of Δ9-tetrahydrocannabinol (THC) on the reproductive system in nude rats with special emphasis on how Δ9-THC impacts the vascularization of testes which in turn indirectly influences fertility. Basically, Δ9-tetrahydrocannabinol (THC) causes not only negative (psychoactive) effects in the human body as cannabinole administration in medical use (dose-dependent) offers multiple new treatment opportunities such as pain relief or containment of various cancers. Concerning the reproductive system it strongly influences CB-receptors along the hypothalamic-pituitary-gonadal axis resulting in reduced plasma testosterone levels. There is also altered sperm quality parameters reported such as sperm motility or sperm count. On the other hand Δ9-THC effects endothelial growth factors (VEGF, Ang-1 etc.) respectively acts on their specific receptors which in turn modify angiogenesis and vascularization of tissues and organs (e.g. tumorous tissues). This leads to new therapeutical strategies in the suppression of various cancers by inhibiting (neo-)vascularization and in turn famishment of tumorous tissues (lack of nutrition supply). Here we studied the micro-vascularization of gonads in a long-term THC-treated nude rat model by vascular corrosion casting, SEM and 3D-morphometry.

  13. Hypoxia-ischemia and retinal ganglion cell damage

    Charanjit Kaur


    Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

  14. Retinal oxygen extraction in humans

    René M. Werkmeister; Doreen Schmidl; Gerold Aschinger; Veronika Doblhoff-Dier; Stefan Palkovits; Magdalena Wirth; Gerhard Garhöfer; Linsenmeier, Robert A.; Rainer A. Leitgeb; Leopold Schmetterer


    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal b...

  15. A novel registration method for retinal images based on local features

    Chen, Jian; R Theodore Smith; Tian, Jie; Laine, Andrew F


    Sometimes it is very hard to automatically detect the bifurcations of vascular network in retinal images so that the general feature based registration methods will fail to register two images. In order to solve this problem, we developed a novel local feature based retinal image registration method. We first detect the corner points instead of bifurcations since corner points are sufficient and uniformly distributed in the overlaps. Second, a novel highly distinctive local feature is extract...

  16. Clinical trials in branch retinal vein occlusion

    Tandava Krishnan Panakanti


    Full Text Available Branch retinal vein occlusion (BRVO is the second most common retinal vascular disorder. The management of macular edema has changed considerably over time. The laser is considered the gold standard treatment for over two decades. However, visual recovery with laser is usually slow and incomplete. The advent of intravitreal agents, specifically anti-vascular endothelial growth factors (VEGF have heralded a new era which promises rapid recovery of vision and quality of vision. Randomized clinical trials have reported optimal results with anti-VEGF agents (ranibizumab, bevacizumab, and aflibercept compared to laser therapy or steroids. However, nearly 50% of the patients require repeat intravitreal anti-VEGF therapy up to 4 years after initiating therapy to sustain the visual gains. The adverse events (systemic and ocular of these agents are minimal. Monotherapy with anti-VEGF agents have been found to provide better results than any combination with laser. This review article summarizes evidence from randomized controlled trials evaluating treatment options for the treatment of macular edema secondary to BRVO with a special focus on anti-VEGF therapy.

  17. Safranal, a saffron constituent, attenuates retinal degeneration in P23H rats.

    Laura Fernández-Sánchez

    Full Text Available Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that administration of safranal to homozygous P23H line-3 rats preserves both photoreceptor morphology and number. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions in safranal-treated versus non-treated animals. Furthermore, the capillary network in safranal-treated animals was preserved, unlike that found in untreated animals. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa.

  18. Retinal vein occlusion in Benin City, Nigeria

    Odarosa M Uhumwangho


    Full Text Available Background: Retinal vein occlusion (RVO is the most common occlusive retinal vascular disorder and results in varying degrees of visual loss. Aim: To determine the pattern of presentation, risk factors, and treatment outcomes in a group of patients with RVO seen in a tertiary hospital in Nigeria. Materials and Methods: Medical records of patients who presented to the University of Benin Teaching Hospital, Benin City, Nigeria in whom a diagnosis of RVO was made over a 5 years period were reviewed. Data obtained were analyzed with the GraphPad Instat Software, Inc. version V2.05a program, San Diego, Califonia and a P < 0.05 considered significant. Results: There were 20 patients made of 14 (70.0% males and 6 (30.0% females with a mean age of 62.7 ± 10.4 years. There were 15 (68.2% eyes with central RVO, 3 (13.6% eyes with branch RVO, and 4 (18.2% eyes with hemi RVO. Bilateral involvement occurred in 2 (10.0% patients. Risk factors included hypertension 14 (70.0%, diabetes mellitus 9 (45.0%, and glaucoma 5 (22.7%. Multiple risk factors were present in 14 (70.0% patients. Complications included macula edema 15 (68.2%, retinal neovascularization 5 (22.7%, neovascular glaucoma 3 (13.6%, and vitreous hemorrhage 2 (9.1%. Eyes which had definitive treatment with intravitreal antivascular endothelial growth factors and laser photocoagulation for macula edema and retinal neovascularization, respectively, had better visual acuity compared to eyes which did not receive these treatment, P = 0.002. Conclusion: The incidence and visual loss that occurs from RVO can be reduced by modifying known risk factors and early institution of appropriate therapy for complications that occur.

  19. Retinal Ganglion Cell Dendritic Atrophy in DBA/2J Glaucoma

    Williams, Pete A.; Howell, Gareth R.; Barbay, Jessica M.; Braine, Catherine E.; Sousa, Gregory L.; John, Simon W. M.; Morgan, James E.


    Glaucoma is a complex disease affecting an estimated 70 million people worldwide, characterised by the progressive degeneration of retinal ganglion cells and accompanying visual field loss. The common site of damage to retinal ganglion cells is thought to be at the optic nerve head, however evidence from other optic neuropathies and neurodegenerative disorders suggests that dendritic structures undergo a prolonged period of atrophy that may accompany or even precede soma loss and neuronal cel...

  20. Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking

    Chizzolini, Marzio; Galan, Alessandro; Milan, Elisabeth; Sebastiani, Adolfo; Costagliola, Ciro; Parmeggiani, Francesco


    Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals ...

  1. Risk factor profile in retinal detachment

    Azad Raj; Nayak B; Sharma Y; Tiwari Hem; Khosla P


    150 cases of retinal detachment comprising 50 patients each of bilateral retinal detachment, unilateral retinal detachment without any retinal lesions in the fellow eve and unilateral retinal detachment with retinal lesions in the fellow eye were studied and the various associated risk factors were statistically analysed. The findings are discussed in relation to their aetiological and prognostic significance in the different types of retinal detachment. Based on these observations certain gu...

  2. Vascular MR

    This project investigates cardiac gated gradient echo pulses sequences for vascular MR imaging. These pulse sequences have been used to acquire and display MR projection angiograms. The authors have applied these methods in two distinct populations of patients for evaluation and comparison with standard angiography. Twenty patients with abdominal aortic aneurysms, and 35 patients with aortoiliac atherosclerotic disease or peripheral vascular disease were investigated using this method and the results are presented

  3. Vascular Dementia

    Maria Alekseyevna Cherdak; O. V. Uspenskaya


    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment ...

  4. Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa.

    Roche, Sarah L; Wyse-Jackson, Alice C; Byrne, Ashleigh M; Ruiz-Lopez, Ana M; Cotter, Thomas G


    Mouse models of retinitis pigmentosa (RP) are essential tools in the pursuit to understand fully what cell types and processes underlie the degeneration observed in RP. Knowledge of these processes is required if we are to develop successful therapies to treat this currently incurable disease. We have used the rd10 mouse model of RP to study retinal morphology prior to photoreceptor loss, using immunohistochemistry and confocal microscopy on cryosections, since little is known about how the mutation affects the retina during this period. We report novel findings that the mutation in the rd10 mouse results in retinal abnormalities earlier than was previously thought. Defects in rod and cone outer segments, bipolar cells, amacrine cells and photoreceptor synapses were apparent in the retina during early stages of postnatal retinal development and prior to the loss of photoreceptors. Additionally, we observed a dramatic response of glial cells during this period. Microglia responded as early as postnatal day (P) 5; ?13 days before any photoreceptor loss is detected with Müller glia and astrocytes exhibiting changes from P10 and P15 respectively. Overall, these findings present pathological aspects to the postnatal development of the rd10 retina, contributing significantly to our understanding of disease onset and progression in the rd10 mouse and provide a valuable resource for the study of retinal dystrophies. PMID:27160072

  5. Valacyclovir in the treatment of acute retinal necrosis

    Taylor Simon RJ


    Full Text Available Abstract Background To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN. Methods This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA at final follow-up, retinal detachment and development of recurrent or second eye disease. Results Retinitis resolved in ten of ten (100% affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60% of eyes. 3/10 eyes (30% developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks. Conclusions Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.

  6. Multimodal Imaging in Hereditary Retinal Diseases

    Francesco Pichi


    Full Text Available Introduction. In this retrospective study we evaluated the multimodal visualization of retinal genetic diseases to better understand their natural course. Material and Methods. We reviewed the charts of 70 consecutive patients with different genetic retinal pathologies who had previously undergone multimodal imaging analyses. Genomic DNA was extracted from peripheral blood and genotyped at the known locus for the different diseases. Results. The medical records of 3 families of a 4-generation pedigree affected by North Carolina macular dystrophy were reviewed. A total of 8 patients with Stargardt disease were evaluated for their two main defining clinical characteristics, yellow subretinal flecks and central atrophy. Nine male patients with a previous diagnosis of choroideremia and eleven female carriers were evaluated. Fourteen patients with Best vitelliform macular dystrophy and 6 family members with autosomal recessive bestrophinopathy were included. Seven patients with enhanced s-cone syndrome were ascertained. Lastly, we included 3 unrelated patients with fundus albipunctatus. Conclusions. In hereditary retinal diseases, clinical examination is often not sufficient for evaluating the patient’s condition. Retinal imaging then becomes important in making the diagnosis, in monitoring the progression of disease, and as a surrogate outcome measure of the efficacy of an intervention.

  7. Activation of retinal microglia rather than microglial cell density correlates with retinal neovascularization in the mouse model of oxygen-induced retinopathy

    Martin Gottfried


    Full Text Available Abstract Background Retinal neovascularization has been intensively investigated in the mouse model of oxygen-induced retinopathy (OIR. Here, we studied the contribution of microglial cells to vascular regression during the hyperoxic phase and to retinal neovascularization during the hypoxic phase. Methods Mice expressing green fluorescent protein (GFP under the Cx3cr1 promoter labeling microglial cells were kept in 75% oxygen from postnatal day 7 (P7 to P12. Microglial cell density was quantified at different time points and at different retinal positions in retinal flat mounts. Microglial activation was determined by the switch from ramified to amoeboid cell morphology which correlated with the switch from lectin negative to lectin positive staining of GFP positive cells. Results Microglial cell density was constant in the peripheral region of the retina. In the deep vascular layer of the central region, however, it declined 14 fold from P12 to P14 and recovered afterwards. Activated microglial cells were found in the superficial layer of the central avascular zone from P8 to P12 and from P16 to P18. In addition, hyalocytes were found in the vitreal layer in the central region and their cell density decreased over time. Conclusion Density of microglial cells does not correlate with vascular obliteration or revascularization. But the time course of the activation of microglia indicates that they may be involved in retinal neovascularization during the hypoxic phase.

  8. Retinal tolerance to dyes

    Lüke, C; Lüke, M; Dietlein, T S; Hueber, A; Jordan, J; Sickel, W.; Kirchhof, B


    Background: Dye solutions for intraoperative staining of epiretinal membranes and the internal limiting membrane improve the visualisation of these thin structures and facilitate their removal. In the present study the authors investigated the effects of indocyanine green 0.05%, trypan blue 0.15%, and patent blue 0.48% on bovine retinal function.

  9. Retinal artery occlusion

    ... artery occlusion; Branch retinal artery occlusion; CRAO; BRAO Images Retina References Sanborn GE, Magargal LE. Arterial obstructive disease ... A.M. Editorial team. Related MedlinePlus Health Topics ... audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  10. Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

    Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

  11. Treatment of macular edema due to retinal vein occlusions

    Channa R


    Full Text Available Roomasa Channa, Michael Smith, Peter A CampochiaroDepartments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Retinal vein occlusion (RVO is a prevalent retinal vascular disease, second only to diabetic retinopathy. Previously there was no treatment for central retinal vein occlusion (CRVO and patients were simply observed for the development of severe complications, generally resulting in poor visual outcomes. The only treatment for branch vein occlusion (BRVO was grid laser photocoagulation, which reduces edema very slowly and provides benefit in some, but not all patients. Within the past year, clinical trials have demonstrated the effects of three new pharmacologic treatments, ranibizumab, triamcinolone acetonide, and dexamethasone implants. The benefit/risk ratio is best for intraocular injections of ranibizumab, making this first-line therapy for most patients with CRVO or BRVO, while intraocular steroids are likely to play adjunctive roles. Standard care for patients with RVO has changed and will continue to evolve as results with other new agents are revealed.Keywords: vascular endothelial growth factor, triamcinolone acetonide, dexamethosone implant, sustained release, vascular leakage, ischemia

  12. Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

    Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T Michael; Baehr, Wolfgang; Ding, Xi-Qin


    Photoreceptors degenerate in a wide array of hereditary retinal diseases and age-related macular degeneration. There is currently no treatment available for retinal degenerations. While outnumbered roughly 20:1 by rods in the human retina, it is the cones that mediate color vision and visual acuity, and their survival is critical for vision. In this communication, we investigate whether thyroid hormone (TH) signaling affects cone viability in retinal degeneration mouse models. TH signaling is...

  13. Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice.

    McLenachan, Samuel; Magno, Aaron Len; Ramos, David; Catita, Joana; McMenamin, Paul G; Chen, Fred Kuanfu; Rakoczy, Elizabeth Piroska; Ruberte, Jesus


    The mouse retina is a commonly used animal model for the study of pathogenesis and treatment of blinding retinal vascular diseases such as diabetic retinopathy. In this study, we aimed to characterize normal and pathological variations in vascular anatomy in the mouse retina using fluorescein angiography visualized with scanning laser ophthalmoscopy and optical coherence tomography (SLO-OCT). We examined eyes from C57BL/6J wild type mice as well as the Ins2(Akita) and Akimba mouse models of diabetic retinopathy using the Heidelberg Retinal Angiography (HRA) and OCT system. Angiography was performed on three focal planes to examine distinct vascular layers. For comparison with angiographic data, ex vivo analyses, including Indian ink angiography, histology and 3D confocal scanning laser microscopy were performed in parallel. All layers of the mouse retinal vasculature could be readily visualized during fluorescein angiography by SLO-OCT. Blood vessel density was increased in the deep vascular plexus (DVP) compared with the superficial vascular plexus (SVP). Arteriolar and venular typologies were established and structural differences were observed between venular types. Unexpectedly, the hyaloid artery was found to persist in 15% of C57BL/6 mice, forming anastomoses with peripheral retinal capillaries. Fluorescein leakage was easily detected in Akimba retinae by angiography, but was not observed in Ins2(Akita) mice. Blood vessel density was increased in the DVP of 6 month old Ins2(Akita) mice, while the SVP displayed reduced branching in precapillary arterioles. In summary, we present the first comprehensive characterization of the mouse retinal vasculature by SLO-OCT fluorescein angiography. Using this clinical imaging technique, we report previously unrecognized variations in C57BL/6J vascular anatomy and novel features of vascular retinopathy in the Ins2(Akita) mouse model of diabetes. PMID:26122048

  14. Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury.

    Sweigard, J Harry; Matsumoto, Hidetaka; Smith, Kaylee E; Kim, Leo A; Paschalis, Eleftherios I; Okonuki, Yoko; Castillejos, Alexandra; Kataoka, Keiko; Hasegawa, Eiichi; Yanai, Ryoji; Husain, Deeba; Lambris, John D; Vavvas, Demetrios; Miller, Joan W; Connor, Kip M


    Degeneration of photoreceptors is a primary cause of vision loss worldwide, making the underlying mechanisms surrounding photoreceptor cell death critical to developing new treatment strategies. Retinal detachment, characterized by the separation of photoreceptors from the underlying retinal pigment epithelium, is a sight-threatening event that can happen in a number of retinal diseases. The detached photoreceptors undergo apoptosis and programmed necrosis. Given that photoreceptors are nondividing cells, their loss leads to irreversible visual impairment even after successful retinal reattachment surgery. To better understand the underlying disease mechanisms, we analyzed innate immune system regulators in the vitreous of human patients with retinal detachment and correlated the results with findings in a mouse model of retinal detachment. We identified the alternative complement pathway as promoting early photoreceptor cell death during retinal detachment. Photoreceptors down-regulate membrane-bound inhibitors of complement, allowing for selective targeting by the alternative complement pathway. When photoreceptors in the detached retina were removed from the primary source of oxygen and nutrients (choroidal vascular bed), the retina became hypoxic, leading to an up-regulation of complement factor B, a key mediator of the alternative pathway. Inhibition of the alternative complement pathway in knockout mice or through pharmacological means ameliorated photoreceptor cell death during retinal detachment. Our current study begins to outline the mechanism by which the alternative complement pathway facilitates photoreceptor cell death in the damaged retina. PMID:26203084

  15. Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy.

    Patel, C; Xu, Z; Shosha, E; Xing, J; Lucas, R; Caldwell, R W; Caldwell, R B; Narayanan, S P


    Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. New-born C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

  16. Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK phosphorylation in renal and vascular dysfunction

    Gupta Akanksha


    Full Text Available Abstract Background In the present study we tested the hypothesis that progression of streptozotocin (STZ-induced diabetes (14-days to 28-days would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK phosphorylation in kidneys and thoracic aorta. Methods Male Sprague Dawley rats (350–400 g were randomized into three groups: sham (N = 6, 14-days diabetic (N = 6 and 28-days diabetic rats (N = 6. Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V. on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat. Results The diabetic rats lost body weight at both 14-days (-10% and 28-days (-13% more significantly as compared to sham (+10% group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS, prepro endothelin-1 (preproET-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. Conclusion The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.

  17. Reduction of homocysteine in elderly with heart failure improved vascular function and blood pressure control but did not affect inflammatory activity

    Andersson, Sven; Edvinsson, Marie-Louise; Edvinsson, Lars


    the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed...... before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory...

  18. Vascular Remodeling in Experimental Hypertension

    Norma R. Risler


    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  19. Bietti crystalline retinal dystrophy with subfoveal neurosensory detachment and congenital tortuosity of retinal vessels: case report.

    Padhi, Tapas Ranjan; Kesarwani, Siddharth; Jalali, Subhadra


    A 34-year-old man presented with reduction and distortion of vision in both the eyes. The best-corrected vision was 20/20 parts, N6 in either eye. The external and slit lamp examination of both the eyes was unremarkable. The fundus examination showed multiple intraretinal crystalline deposits at the posterior pole, extending up to midperiphery, tortuous retinal blood vessels with S-shaped deflections, and absent foveal reflex in both the eyes. There were no corneal crystals, and the color vision was defective in both the eyes. Fundus autofluorescence and fundus fluorescein angiogram (FFA) were suggestive of geographic areas of retinal pigment epithelium (RPE) and choriocapillary (CC) loss. OCT revealed subfoveal neurosensory detachment. Flash ERG and EOG were normal except for a slight decrease in amplitude and delay in latency of pattern ERG waveforms. The Humphrey's visual field showed paracentral scotoma with reduction in the amplitude of waveforms from the corresponding area in the multifocal ERG in both the eyes. Systemic evaluation for crystalline retinopathy was unremarkable. He was diagnosed to be a case of Bietti crystalline retinopathy (local/regional variant). The subfoveal neurosensory detachment could represent early RPE dysfunction caused by these crystals and could account for the mild visual disturbance in both the eyes. Retinal vascular tortuosity and neurosensory detachment seen in this case is the first time to be reported in literature. PMID:21611771

  20. Small Animal Retinal Imaging

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  1. Inherited Retinal Degenerative Disease Registry


    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  2. Retinal flow cytometer

    Alt, C.; Veilleux, I.; Lee, H; Pitsillides, C. M.; D. Côté; Lin, C.P.


    The in vivo flow cytometer is an instrument capable of continuous, real-time monitoring of fluorescently labeled cells in the circulation without the need to draw blood samples. However, the original system probes a single vessel in the mouse ear; the small sample volume limits the sensitivity of the technique. We describe an in vivo retinal flow cytometer that simultaneously probes five artery–vein pairs in the mouse eye by circularly scanning a small laser spot rapidly around the optic nerv...

  3. Aphakic retinal detachment.

    Le Mesurier, R; Vickers, S; Booth-Mason, S; Chignell, A H


    A study of 132 cases of aphakic retinal detachment (ARD) following mainly intracapsular cataract surgery has been made. Forty-nine cases (37%) were found to have vitreous incarcerated into the cataract section out of a total of 54 (41%) cases who had suffered a vitreous complication during cataract surgery. A study of the characteristics of ARD reveals that those cases having had a vitreous complication in the management of their cataracts are more likely to develop detachment within three mo...

  4. Spectral domain optical coherence tomography features of multiple subfoveal retinal pigment epithelial tears after intravitreal bevacizumab

    Chalam Kakarla; Murthy Ravi; Gupta Shailesh; Brar Vikram


    Retinal pigment epithelial (RPE) tear has been described to occur spontaneously, after laser photocoagulation and in recent times, after intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. In the latter case, the rapid contraction of the choroidal vascular membrane underneath a serous RPE detachment is believed to be the underlying cause. Preservation of good visual acuity after the occurrence of RPE tear with continued use of intravitreal VEGF agents has been rep...

  5. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

    Cheryl A Arcinue

    Full Text Available To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula compared with age-matched HIV-negative controls.Cohort of patients with known HIV under CART (combination Antiretroviral Therapy treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT to assess retinal layers and retinal thickness.Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior, the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2. A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea. We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer was also significantly thickened in all the different locations scanned compared with HIV-negative controls.Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

  6. VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis

    Huang, Delong; Zhao, Chen; Ju, Rong; Kumar, Anil; Tian, Geng; Huang, Lijuan; Zheng, Lei; Li, Xianglin; Liu, Lixian; Wang, Shasha; Ren, Xiangrong; Ye, Zhimin; Chen, Wei; Xing, Liying; Chen, Qishan; Gao, Zhiqin; Mi, Jia; Tang, Zhongshu; Wang, Bin; Zhang, Shuping; Lee, Chunsik; Li, Xuri


    Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration. PMID:27189805

  7. VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis.

    Huang, Delong; Zhao, Chen; Ju, Rong; Kumar, Anil; Tian, Geng; Huang, Lijuan; Zheng, Lei; Li, Xianglin; Liu, Lixian; Wang, Shasha; Ren, Xiangrong; Ye, Zhimin; Chen, Wei; Xing, Liying; Chen, Qishan; Gao, Zhiqin; Mi, Jia; Tang, Zhongshu; Wang, Bin; Zhang, Shuping; Lee, Chunsik; Li, Xuri


    Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy and other ocular neovascular diseases. It is therefore urgent to have a better understanding of the function of VEGF-B in these pathologies. Here, we report that both streptozotocin (STZ)-induced diabetes in rats and Macugen intravitreal injection in mice leads to retinal apoptosis in retinal ganglion cell and outer nuclear layers respectively. Importantly, VEGF-B treatment by intravitreal injection markedly reduced retinal apoptosis in both models. We further reveal that VEGF-B and its receptors, vascular endothelial growth factor 1 (VEGFR1) and neuropilin 1 (NP1), are abundantly expressed in rat retinae and choroids and are upregulated by high glucose with concomitant activation of Akt and Erk. These data highlight an important function of VEGF-B in protecting retinal cells from apoptosis induced by hyperglycemia and VEGF-A inhibition. VEGF-B may therefore have a therapeutic potential in treating various retinal degenerative diseases, and modulation of VEGF-B activity in the eye needs careful consideration. PMID:27189805

  8. Clinical and immunological features of retinal vasculitis in systemic diseases

    Paović Jelena


    . Conclusion. Systemic diseases such as Behcet's syndrome, collagen vascular diseases, systemic granulomatous diseases (sarcoidosis and tuberculosis were the main causes of retinal vasculitis. Knowledge of the symptomatology and pathogenesis of retinal vasculitis is of the major significance for the diagnosis and therapy of the disease.

  9. What Is Vascular Disease?

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  10. Diabetes and Vascular Disease

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...