Screening of diabetics for retinopathy by ophthalmic opticians.

Diabetes mellitus is a major cause of blindness in England and Wales in those aged between 30 and 64. Photocoagulation can frequently prevent blindness provided the retinopathy is detected at an appropriate stage but unfortunately the benefits are small if the changes are advanced. Early detection of diabetic retinopathy by regular examination is needed. We have shown that ophthalmic opticians have the skill to detect retinal changes at a treatable stage. Out of 844 eye checks, 80 were reported by ophthalmic opticians to justify referral to an ophthalmologist and 20 of these required photocoagulation treatment. Of a sample of 197 patients rechecked by an ophthalmologist reported by ophthalmic opticians not to justify referral, only one needed treatment. With local agreement this system of detecting retinopathy could be easily applied anywhere in the United Kingdom. No extra personnel or facilities are needed.     

Detection of Neovascularization Based on Fractal and Texture Analysis with Interaction Effects in Diabetic Retinopathy

Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.     

The English national risk-reduction programme for preservation of sight in diabetes

This paper discusses the new national guidelines for a systematic screening programme to detect sight-threatening diabetic retinopathy in the population of people with diabetes in England. A review of the literature examines the evidence base to support screening interventions and effective management and treatments in diabetic retinopathy. The current evidence supports the establishment of a digital retinal photography system using pupil dilation. A Policy Advisory Group has been formulated by the National Screening Committee to guide the meeting of this target in England. A conclusion is made that with increased effort and organisation, health care professionals can ensure that the screening programme is successfully implemented and rates of visual impairment and blindness caused by diabetic retinopathy can be reduced significantly.     

The isolation and characterization of β-glucogallin as a novel aldose reductase inhibitor from Emblica officinalis

Diabetes mellitus is recognized as a leading cause of new cases of blindness. The prevalence of diabetic eye disease is expected to continue to increase worldwide as a result of the dramatic increase in the number of people with diabetes. At present, there is no medical treatment to delay or prevent the onset and progression of cataract or retinopathy, the most common causes of vision loss in diabetics. The plant Emblica officinalis (gooseberry) has been used for thousands of years as a traditional Indian Ayurvedic preparation for the treatment of diabetes in humans. Extracts from this plant have been shown to be efficacious against the progression of cataract in a diabetic rat model. Aldose reductase (ALR2) is implicated in the development of secondary complications of diabetes including cataract and, therefore, has been a major drug target for the development of therapies to treat diabetic disease. Herein, we present the bioassay-guided isolation and structure elucidation of 1-O-galloyl-β-D-glucose (β-glucogallin), a major component from the fruit of the gooseberry that displays selective as well as relatively potent inhibition (IC(50) = 17 μM) of AKR1B1 in vitro. Molecular modeling demonstrates that this inhibitor is able to favorably bind in the active site. Further, we show that β-glucogallin effectively inhibits sorbitol accumulation by 73% at 30 μM under hyperglycemic conditions in an ex-vivo organ culture model of lenses excised from transgenic mice overexpressing human ALR2 in the lens. This study supports the continued development of natural products such as β-glucogallin as therapeutic leads in the development of novel therapies to treat diabetic complications such as cataract.     

The English national risk-reduction programme for preservation of sight in diabetes

This paper discusses the new national guidelines for a systematic screening programme to detect sight-threatening diabetic retinopathy in the population of people with diabetes in England. A review of the literature examines the evidence base to support screening interventions and effective management and treatments in diabetic retinopathy. The current evidence supports the establishment of a digital retinal photography system using pupil dilation. A Policy Advisory Group has been formulated by the National Screening Committee to guide the meeting of this target in England. A conclusion is made that with increased effort and organisation, health care professionals can ensure that the screening programme is successfully implemented and rates of visual impairment and blindness caused by diabetic retinopathy can be reduced significantly. (Mol Cell Biochem 261: 183–185, 2004)     

Ischemic Conditioning Protects from Axoglial Alterations of the Optic Pathway Induced by Experimental Diabetes in Rats

Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.     

Use of mobile screening unit for diabetic retinopathy in rural and urban areas.

OBJECTIVES--To compare the effectiveness of a mobile screening unit with a non-mydriatic polaroid camera in detecting diabetic retinopathy in rural and urban areas. To estimate the cost of the service. DESIGN--Prospective data collection over two years of screening for diabetic retinopathy throughout Tayside. SETTING--Tayside region, population 390,000, area 7770 km2. SUBJECTS--961 patients in rural areas and 1225 in urban areas who presented for screening. MAIN OUTCOME MEASURES--Presence of diabetic retinopathy, need for laser photocoagulation, age, duration of diabetes, and diabetic treatment. RESULTS--Compared with diabetic patients in urban areas, those in rural areas were less likely to attend a hospital based diabetic clinic (46% (442) v 86% (1054), p < 0.001); less likely to be receiving insulin (260 (27%) v 416 (34%), p < 0.001 and also after correction for differences in age distribution); more likely to have advanced (maculopathy or proliferative retinopathy) diabetic retinopathy (13% (122) v 7% (89), p < 0.001); and more likely to require urgent laser photocoagulation for previously unrecognised retinopathy (1.4% (13) v 0.5% (6), p < 0.02). The screening programme cost 10 pounds per patient screened and 1000 pounds per patient requiring laser treatment. CONCLUSION--The mobile diabetic eye screening programme detected a greater prevalence of advanced retinopathy in diabetic patients living in rural areas. Patients in rural areas were also more likely to need urgent laser photocoagulation. Present screening procedures seem to be less effective in rural areas and rural patients may benefit more from mobile screening units than urban patients.     

Beta‐lapachone inhibits pathological retinal neovascularization in oxygen‐induced retinopathy via regulation of HIF‐1α

Retinal neovascularization in retinopathy of prematurity (ROP) is the most common cause of blindness for children. Despite evidence that hypoxia inducible factor (HIF)‐1α ‐VEGF axis is associated with the pathogenesis of ROP, the inhibitors of HIF‐1α have not been established as a therapeutic target in the control of ROP pathophysiology. We investigated the hypothesis that degradation of HIF‐1α as a master regulator of angiogenesis in hypoxic condition, using β‐lapachone, would confer protection against hypoxia‐induced retinopathy without affecting physiological vascular development in mice with oxygen‐induced retinopathy (OIR), an animal model of ROP. The effects of β‐lapachone were examined after intraocular injection in mice with OIR. Intraocular administration of β‐lapachone resulted in significant reduction in hypoxia‐induced retinal neovascularization without retinal toxicity or perturbation of developmental retinal angiogenesis. Our results demonstrate that HIF‐1α–mediated VEGF expression in OIR is associated with pathological neovascularization, not physiological angiogenesis. Thus, strategies blocking HIF‐1α in the developing eye in the pathological hypoxia could serve as a novel therapeutic target for ROP.     

Automated Multi-Lesion Detection for Referable Diabetic Retinopathy in Indigenous Health Care

Diabetic Retinopathy (DR) is a complication of diabetes mellitus that affects more than one-quarter of the population with diabetes, and can lead to blindness if not discovered in time. An automated screening enables the identification of patients who need further medical attention. This study aimed to classify retinal images of Aboriginal and Torres Strait Islander peoples utilizing an automated computer-based multi-lesion eye screening program for diabetic retinopathy. The multi-lesion classifier was trained on 1,014 images from the São Paulo Eye Hospital and tested on retinal images containing no DR-related lesion, single lesions, or multiple types of lesions from the Inala Aboriginal and Torres Strait Islander health care centre. The automated multi-lesion classifier has the potential to enhance the efficiency of clinical practice delivering diabetic retinopathy screening. Our program does not necessitate image samples for training from any specific ethnic group or population being assessed and is independent of image pre- or post-processing to identify retinal lesions. In this Aboriginal and Torres Strait Islander population, the program achieved 100% sensitivity and 88.9% specificity in identifying bright lesions, while detection of red lesions achieved a sensitivity of 67% and specificity of 95%. When both bright and red lesions were present, 100% sensitivity with 88.9% specificity was obtained. All results obtained with this automated screening program meet WHO standards for diabetic retinopathy screening.     

Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression

The incidence of age-related macular degeneration (AMD), the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1) is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF) and its antagonist pigment epithelium-derived factor (PEDF) genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg) prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months) caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.     

Calpain-5 Mutations Cause Autoimmune Uveitis, Retinal Neovascularization, and Photoreceptor Degeneration

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. We identified two different missense mutations in the CAPN5 gene in three ADNIV kindreds. CAPN5 encodes calpain-5, a calcium-activated cysteine protease that is expressed in retinal photoreceptor cells. Both mutations cause mislocalization from the cell membrane to the cytosol, and structural modeling reveals that both mutations lie within a calcium-sensitive domain near the active site. CAPN5 is only the second member of the large calpain gene family to cause a human Mendelian disorder, and this is the first report of a specific molecular cause for autoimmune eye disease. Further investigation of these mutations is likely to provide insight into the pathophysiologic mechanisms of common diseases ranging from autoimmune disorders to diabetic retinopathy.     

Homoisoflavanone inhibits retinal neovascularization through cell cycle arrest with decrease of cdc2 expression

Neovascularization in the eye is the most common cause of blindness in all age groups; retinopathy of prematurity (ROP), diabetic retinopathy, and age-related macular degeneration. Despite current advances in surgical treatments, ROP remains as the most serious problem of vision loss in children. Here, we report that homoisoflavanone, a natural product from Cremastra appendiculata, significantly reduces retinal neovascularization in a mouse model of ROP. Homoisoflavanone inhibited the cell growth of HUVECs, but its cytotoxic effect was not observed in a concentration range of 1-20 microM. HUVECs population gradually increased in G2/M phase and reduced in G0/G1 and S phases after exposure to the compound. Homoisoflavanone decreased the level of cdc2 expression whereas the level of p21WAF1 expression was increased in a dose-dependent manner. These data demonstrate that homoisoflavanone could inhibit retinal neovascularization and be applied in the treatment of other vasoproliferative retinopathies.     

The First Rapid Assessment of Avoidable Blindness (RAAB) in Thailand

Background

The majority of vision loss is preventable or treatable. Population surveys are crucial for planning, implementation, and monitoring policies and interventions to eliminate avoidable blindness and visual impairments. This is the first rapid assessment of avoidable blindness (RAAB) study in Thailand.

Methods

A cross-sectional study of a population in Thailand age 50 years old or over aimed to assess the prevalence and causes of blindness and visual impairments. Using the Thailand National Census 2010 as the sampling frame, a stratified four-stage cluster sampling based on a probability proportional to size was conducted in 176 enumeration areas from 11 provinces. Participants received comprehensive eye examination by ophthalmologists.

Results

The age and sex adjusted prevalence of blindness (presenting visual acuity (VA) <20/400), severe visual impairment (VA <20/200 but ≥20/400), and moderate visual impairment (VA <20/70 but ≥20/200) were 0.6% (95% CI: 0.5–0.8), 1.3% (95% CI: 1.0–1.6), 12.6% (95% CI: 10.8–14.5). There was no significant difference among the four regions of Thailand. Cataract was the main cause of vision loss accounted for 69.7% of blindness. Cataract surgical coverage in persons was 95.1% for cut off VA of 20/400. Refractive errors, diabetic retinopathy, glaucoma, and corneal opacities were responsible for 6.0%, 5.1%, 4.0%, and 2.0% of blindness respectively.

Conclusion

Thailand is on track to achieve the goal of VISION 2020. However, there is still much room for improvement. Policy refinements and innovative interventions are recommended to alleviate blindness and visual impairments especially regarding the backlog of blinding cataract, management of non-communicative, chronic, age-related eye diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy, prevention of childhood blindness, and establishment of a robust eye health information system.     

Visual problems in the elderly population and implications for services.

OBJECTIVE--To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN--Cross sectional random sample survey. SETTING--Inner London health centre. SUBJECTS--Random sample of people aged 65 and over taken from practice''s computerised age-sex register. MAIN OUTCOME MEASURES--Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS--207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION--There seems to be a considerable amount of undetected ocular disease in elderly people in the community.     

Potent antiemetic effects of the new serotonin antagonists.

Diabetic retinopathy progresses through three distinct stages. A rational approach to management is based on an understanding of the pathophysiology of each stage. Based on the results of national multicentered clinical trials of laser photocoagulation and other treatments, advances in our understanding of the pathogenesis and treatment can now make a dramatic impact on blindness in the diabetic population: Panretinal laser photocoagulation treatment can reduce the risk of vision loss from high-risk proliferative diabetic retinopathy by at least 50%. Laser photocoagulation treatment of clinically significant diabetic macular edema can reduce the risk of vision loss by more than 50%. Vitrectomy can restore useful vision to some patients with severe diabetic retinopathy and vitreous hemorrhage with or without an accompanying traction retinal detachment. Diabetes 2000 is a new project sponsored by the American Academy of Ophthalmology, the goal of which is to eliminate preventable blindness from diabetes by the year 2000. As its name implies, Diabetes 2000 will be a long-term project aimed at a specific disease--diabetic retinopathy and its complications. It will provide the latest research findings to ophthalmologists and primary care physicians as the first priority, followed by the education of patients and the general public. Recent advances and treatment guidelines for the medical and surgical treatment of diabetic eye disease will be emphasized through the continuing education of ophthalmologists, other physicians, and allied health professionals. In later phases, educational programs for diabetic persons and the public will be developed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sirtuin1 Over-Expression Does Not Impact Retinal Vascular and Neuronal Degeneration in a Mouse Model of Oxygen-Induced Retinopathy

Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy.     

MicroRNA-410 Reduces the Expression of Vascular Endothelial Growth Factor and Inhibits Oxygen-Induced Retinal Neovascularization

Retinal neovascularization (RNV) is an eye disease that can cause retinal detachment and even lead to blindness. RNV mainly occurs in the elderly population. The pathogenesis of RNV has been previously reported to be highly related to the expression of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF) and other angiogenic factors. It has also been reported that VEGFA and other factors associated with RNV could be regulated by certain microRNAs (miRNA), a group of small non-coding RNAs which are able to regulate the expression of many genes in vivo. Here, we demonstrate that the miRNA miR-410 is highly expressed in mice within two weeks after birth. miR-410 could suppress VEGFA expression through interaction with the 3′UTR of the VEGFA messenger RNA. Overexpressing a miR-410 mimic effectively suppresses VEGFA expression in various cell lines. Further experiments on oxygen-induced retinopathy (OIR) in mice revealed that eye drops containing large amounts of miR-410 efficiently downregulate VEGFA expression, prevent retinal angiogenesis and effectively treat RNV. These results not only show the underlying mechanism of how miR-410 targets VEGFA but also provide a potential treatment strategy for RNV that might be used in the near future.     

糖尿病视网膜病变的基因治疗

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病的主要并发症之一,大量的研究表明DR早期表现为视网膜神经细胞退化性改变,晚期出现新生血管及增殖膜,目前尚没有有效的治疗方法,严重危害患者视力。基因治疗为探索DR的治疗方法提供了新的手段,本文就目前DR的基因治疗研究现状和进展作一综述。     

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective.     

Suppression of GLUT1; A new strategy to prevent diabetic complications

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non‐diabetics. 1,9‐Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein β2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy. J. Cell. Physiol. 228: 251–257, 2013. © 2012 Wiley Periodicals, Inc.