Abnormalities of retinal metabolism in diabetes or experimental galactosemia VIII. Prevention by aminoguanidine

PURPOSE: Aminoguanidine has been found to inhibit the development of some retinal lesions in diabetic rats and diabetic dogs, thereby raising a possibility that the formation of glycation end products (AGEs) may be an essential step in the pathogenesis of the retinopathy. The purpose of this study is to investigate the effect of aminoguanidine administration on other metabolic abnormalities which might be involved in the development of retinopathy in two models of the retinopathy, alloxan diabetes and experimental galactosemia. METHODS: Oxidative stress, nitric oxide (NO) and the activity of protein kinase C (PKC, total activity) were measured in the retina of the rats experimentally diabetic or galactosemic for 2 months. Effect of aminoguanidine administration on the inhibition of hyperglycemia-induced retinal dysmetabolism was investigated. RESULTS: Two months of diabetes or experimental galactosemia in rats resulted in elevation of retinal oxidative stress (increase in thiobarbituric acid reactive substances, TBARS, and decrease in glutathione, GSH), NO, and PKC activity. Aminoguanidine supplementation (2.5 g aminoguanidine/kg rat diet) significantly inhibited each of these abnormalities in retinas of diabetic rats and galactosemic rats, and did so without lowering the blood hexose levels of these animals. CONCLUSIONS: The ability of aminoguanidine to normalize the hyperglycemia-induced increases in retinal oxidative stress, NO and PKC in diabetic rats and galactose-fed rats suggests that these abnormalities may be inter-related in the retina, and that the biochemical mechanism by which aminoguanidine inhibits retinal microvascular disease in diabetes may be complex.     

Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male Experimental Retinal Vein Occlusion Mouse Model

PurposeSemaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction.MethodsWe examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-α and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer.ResultsInduction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-α and semaphorin-related proteins.ConclusionsThese findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.     

Protective effects of triamcinolone acetonide upon the upregulation and phosphorylation of GAP 43 in an animal model of retinopathy of prematurity

Acta Ophthalmol. 2010: 88: e217–e221

Abstract.

Purpose: The aim of the current study was to investigate the effects of triamcinolone acetonide (TA) upon the expression and phosphorylation of growth‐associated protein 43 (GAP 43) in the retinas of oxygen‐induced retinopathy (OIR) rats. Methods: Oxygen‐induced retinopathy was induced by exposing Sprague‐Dawley rats to hyperoxia (80% oxygen) from postnatal (P) days 2–14 and then returning the rats to normoxic conditions. Triamcinolone acetonide or a conditioned saline (control) was injected intravitreally into the right or left eye, respectively, of OIR rats at P15. We then assessed the molecular and histological changes in the expression of GAP 43 and phospho‐GAP 43 in OIR and control rat retinas, and also after treatment with TA by RT‐PCR, Western blotting and immunohistochemistry. Results: Growth‐associated protein 43 mRNA levels were found to be increased by 1.6‐fold (p = 0.001, n = 5) in the retinas of P18 OIR rats compared with the control rats. The protein levels of GAP 43 and phospho‐GAP43 were found to be elevated in the retina of P18 OIR rats (2.40‐ and 2.39‐fold greater than each control, p<0.001, n = 5, respectively). Immunoreactivities of GAP 43 and phospho‐GAP 43 were stronger in the inner plexiform layer in OIR rat retinas compared with the control. However, treatment with TA attenuated GAP 43 and phospho‐GAP 43 upregulation in the OIR retinas. Conclusion: Our results indicate that GAP 43 and phospho‐GAP 43 participate in retinal (potentially pathologic) changes following oxygen‐induced damage. Triamcinolone acetonide protects the retinal damage in relatively hypoxic retinas of OIR rats. Therefore, TA treatment does not induce the expression and phosphorylation of GAP 43 in OIR rat retinas.     

Triamcinolone Acetonide Prevents Enhancement of Hypoxia-induced Neuronal and Inducible Nitric Oxide Synthases in the Retinas of Rats with Oxygen-induced Retinopathy

Purpose

We investigated whether oxygen-induced retinopathy (OIR) results in changes in the protein expression of neuronal and inducible nitric oxide synthases (nNOS and iNOS, respectively) in rat model of OIR. In addition, we evaluated whether treatment of rats with triamcinolone acetonide (TA) prevents this response.

Methods

To promote OIR, Sprague-Dawley rats were exposed to hyperoxia from postnatal day 2 (P2) to P14. They were then returned to normoxia after P15. TA was injected into the right vitreous of P15 rats, while saline was injected into the left vitreous. At P18 the expression of nNOS and iNOS was determined using Western blotting and immunostaining techniques in retinas obtained from control rats.

Results

In P18 OIR rats, the abundance of nNOS and iNOS protein was significantly increased compared with controls. These increases were not observed in the retinas of rats treated with TA. The change in expression of nNOS and iNOS were specific to parvalbumin and glial fibrillary acidic protein-positive cells. Treatment with TA prevented the increased expression of nNOS and iNOS in all samples.

Conclusions

Hypoxia upregulates expression of nNOS and iNOS in OIR rat retinas, which is can be prevented by treatment with TA.     

Metabolomics Analyses of Mouse Retinas in Oxygen-Induced Retinopathy

PurposeRetinal neovascularization is a severe pathological process leading to irreversible blindness. This study aims to identify the altered metabolites and their related pathways that are involved in retinal neovascularization.MethodsTo reveal the global metabolomic profile change in the retinal neovascularization process, an untargeted metabolomics analysis of oxygen-induced retinopathy (OIR) mice retinas was carried out first, followed by the validation of amino acids and their derivatives through a targeted metabolomics analysis. The involved pathways were predicted by bioinformatic analysis.ResultsBy untargeted metabolomics, a total of 58 and 49 metabolites altered significantly in OIR retinas under cationic and anionic modes, respectively. By bioinformatics analysis, “ABC transporters,” “central carbon metabolism in cancer.” and “alanine, aspartate, and glutamate metabolism” were the most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with the changed metabolites. By targeted metabolomics, no significant change was found in the assessed amino acids and their derivatives at postnatal day (P) 12, whereas significantly altered amino acids and their derivatives were recognized at P13, P17, and P42 in OIR retinas.ConclusionsThe metabolomic profile was significantly altered in the neovascularized retinas. In particular, numerous amino acids and their derivatives were significantly changed in OIR retinas. These altered metabolites, together with their associated pathways, might be involved in the pathogenesis of retinal neovascular diseases.     

Expression of thrombospondin‐2 as a marker in proliferative diabetic retinopathy

Purpose: To determine the expression of the endogenous anti‐angiogenic and pro‐fibrotic matricellular protein thrombospondin (TSP)‐2 and its receptors CD36 and CD47 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of TSP‐2 in the retinas of diabetic rats. Methods: Epiretinal membranes from 14 patients with PDR and nine patients with proliferative vitreoretinopathy were studied by immunohistochemistry. Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme‐linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blotting. Results: In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed TSP‐2, CD36 and CD47. In PDR membranes, significant correlations were observed between numbers of blood vessels expressing the panendothelial cell marker CD34 and numbers of blood vessels and stromal cells expressing TSP‐2, CD36 and CD47. The numbers of blood vessels and stromal cells expressing CD34, TSP‐2, CD36 and CD47 were significantly higher in membranes with active neovascularization when compared with those with quiescent disease. Thrombospondin‐2 levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001). Western blot analysis revealed a significant increase in the expression of intact and cleaved TSP‐2 in vitreous samples from PDR patients and in the retinas of diabetic rats compared to nondiabetic controls. Conclusions: Upregulation of TSP‐2 may be a protective mechanism against inflammation and angiogenesis associated with PDR.     

黄芪注射液对模拟高海拔缺氧大鼠视网膜的影响

目的：探究黄芪注射液对模拟高海拔缺氧大鼠视网膜自由基代谢及病理学形态改变的影响。

方法：选取60只健康不伴有眼疾的SD大鼠,依照随机分组法分为黄芪注射液组(干预组)与生理盐水组(对照组),每组各30只。每组大鼠中,随机各选取6只于放入模拟舱前分别腹腔注射黄芪注射液(15mL/kg)与生理盐水(15mL/kg)。注射完30min之后放入5 000m的模拟舱,分别生存2、6、8、12、24h。出舱后立即处死并摘除眼球,用HE染色法观察视网膜形态的改变,比色法测定视网膜SOD和MDA含量。

结果：HE染色示2h时两组视网膜均无形态学改变,随着缺氧时间延长,视网膜各层水肿逐渐加剧,但干预组水肿程度低于对照组。随高海拔缺氧时间的延长,两组SOD活性均下降,组内不同时间点比较,差异均具有统计学意义(P<0.05); 两组MDA的含量均逐渐升高,组内不同时间点比较,差异均具有统计学意义(P<0.05)。两组SOD活性在同时间点进行比较,除2h无统计学意义,其余时间点差异具有统计学意义(P<0.05); 同时间点两组MDA含量进行比较,除2h差异无统计学意义,其余时间点差异具有统计学意义(P<0.05)。

结论：黄芪注射液可以改善高海拔缺氧环境下大鼠视网膜病变的损伤程度,其机制可能与清除自由基、增强SOD的活性,减少脂质过氧化物MDA的含量、增强抗氧化能力有关。     

VEGF localisation in diabetic retinopathy

AIM—To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes.
METHODS—Immunohistochemical localisation of VEGF, using antibodies raised against VEGF₁₆₅ and VEGF_121,165,189, was carried out on specimens of normal human retina (n=15), diabetic retinas ((a) with no overt retinopathy (n=19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n=6), (c) with active proliferative retinopathy (n=6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n=15)), excised diabetic fibrovascular membranes (n=19), and non-diabetic fibrocellular membranes (n=7). The degree and pattern of immunostaining was recorded.
RESULTS—In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF₁₆₅ antibody was generally confined to endothelial cells and perivascular regions while the VEGF_121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined.
CONCLUSIONS—This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Keywords: vascular endothelial growth factor; VEGF; diabetes; diabetic retinopathy     

Unilateral diabetic macular oedema secondary to central retinal vein congestion

PURPOSE: To describe two cases of strictly unilateral diabetic retinopathy with macular edema where the precipitating factor appears to have been retinal venous congestion. METHODS: Retrospective interventional case study. RESULTS: Examination of fundus photographic records demonstrated generalized venous dilation in the affected eyes years in advance of the development of unilateral diabetic macular edema. Relentless progression of edema and visual loss followed despite retinal photocoagulation treatment and ultimately the affected eyes in both patients developed central retinal vein occlusion. The fellow eyes in both patients remained without retinopathy throughout the period of observation. CONCLUSION: The sequential and strictly unilateral appearance of retinal venous dilation, diabetic macular edema, and central retinal vein occlusion in diabetic patients without fellow-eye retinopathy suggests that venous congestion induced the progression from hyperglycemic insult to vascular injury in the affected eyes. Presumably, diabetes may cause retinal vascular dysfunction that results in little or no vascular damage unless venous congestion is present. This supports that venous congestion and increased sensitivity to congestion are important components of the pathogenesis of diabetic macular edema.     

The Predictive Role of Thyroid Hormone Levels for Early Diabetic Retinal Changes in Experimental Rat and Human Diabetes

PurposeIn diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations.MethodsIn rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case–control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs.ResultsA higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs.ConclusionsOur results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.     

Streptozotocin induced diabetic retinopathy in rat and the expression of vascular endothelial growth factor and its receptor

AIM: To investigate the characteristics and criterion of graft rejection in mice model.METHODS: C57BL/6 or BALB/c mice corneal grafts were grafted onto BALB/c hosts. Each group was divided into two subgroups according to the corneal opacity scores 12d after transplantation. The characteristics of opacity and neovascularization were observed. Mice of the 12^th, 50^th day after transplantation, the grafts biopsy of mice in allogeneic group 1, which opacity score exceed 3, were prepared for histological observation and those restore transparent were endothelial stained.RESULTS: There was no difference of corneal opacity score on the 7^th and 12^th day after operation; the histological results had no disparity between syngeneic group and allogeneic group. On the 12^th day after surgery, the turbidity curve was apparent in grafts with opacity score ＜2. Mononuclear cells were shown in grafts with opacity score reached 3 in allogeneic group 1. Different rejection performance was observed in tissue sections on the 50^th day after surgery.CONCLUSION:Grafts, opacity score exceeds 3 from the 7^th to the 12^th day after operation could not be judged as a rejection. We should pay more attention to the variation of grafts opacity since 12d after corneal transplantation.     

Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes—Implications for Retinopathy

PurposeTo investigate the expression of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 in human retina.MethodsHuman post-mortem eyes from 13 non-diabetic control cases and 11 diabetic retinopathy cases were analyzed for the expression of ACE2. To compare the vascular ACE2 expression between different organs that involve in diabetes, the expression of ACE2 was investigated in renal specimens from nondiabetic and diabetic nephropathy patients. Expression of TMPRSS2, a cell-surface protease that facilitates SARS-CoV-2 entry, was also investigated in human nondiabetic retinas. Primary human retinal endothelial cells (HRECs) and primary human retinal pericytes (HRPCs) were further used to confirm the vascular ACE2 expression in human retina.ResultsWe found that ACE2 was expressed in multiple nonvascular neuroretinal cells, including the retinal ganglion cell layer, inner plexiform layer, inner nuclear layer, and photoreceptor outer segments in both nondiabetic and diabetic retinopathy specimens. Strikingly, we observed significantly more ACE2 positive vessels in the diabetic retinopathy specimens. By contrast, in another end-stage organ affected by diabetes, the kidney, ACE2 in nondiabetic and diabetic nephropathy showed apical expression of ACE2 tubular epithelial cells, but no endothelial expression in glomerular or peritubular capillaries. Western blot analysis of protein lysates from HRECs and HRPCs confirmed expression of ACE2. TMPRSS2 expression was present in multiple retinal neuronal cells, vascular and perivascular cells, and Müller glia.ConclusionsTogether, these results indicate that retina expresses ACE2 and TMPRSS2. Moreover, there are increased vascular ACE2 expression in diabetic retinopathy retinas.     

Retinal heparanase expression in streptozotocin-induced diabetic rats

Objective: Heparanase, an endoglycosidase, exhibits strong proangiogenic capacity that can induce vascular endothelial growth factor (VEGF) expression in tumour angiogenesis. The purpose of this study was to evaluate heparanase expression and its relationship with VEGF in streptozotocin (STZ)-induced diabetic rats' retinas.Design: Experimental study.Participants: STZ-induced rats and non-diabetic control rats.Methods: Heparanase expression was initially evaluated in cultured human retinal microvascular endothelial cells (HRECs) under high-glucose conditions by Western blot. Diabetes was induced in Sprague-Dawley rats by STZ intraperitoneal injection. Retinal heparanase expression was assayed in rats by immunohistochemistry. Heparanase inhibitor (phosphomannopentaose sulfate) was administrated to high-glucose-treated HRECs and diabetic rats. VEGF levels were evaluated in HRECs and retinas using enzyme-linked immunosorbent assay.Results: Heparanase expression was increased in HRECs under high-glucose conditions compared with controls (p < 0.01). Immunohistochemical studies indicated that heparanase signals were intense in the retinal vascular endothelia of diabetic rats, but faint in those of nondiabetic control rats. Quantitative analysis showed that heparanase protein expression was increased by 3.2-fold in diabetic rats' retinas compared with nondiabetic rats' retinas (p < 0.01). VEGF level was increased, as was heparanase expression, in high-glucose-treated HRECs and in the retinas of diabetic rats, and these increases were significantly decreased by phosphomannopentaose sulfate administration (p < 0.01).Conclusions: Heparanase expression was upregulated and associated with an increase of VEGF expression in STZ-induced diabetic rat retinas. The data suggest that heparanase may be involved in the development of diabetic retinopathy and represents a possible novel target for therapeutic intervention.     

Vascular Endothelial Growth Factor Gene Polymorphisms and Vitreous Proteome Changes in Diabetic Retinopathy

Abstract

Ischemic retinal diseases, particularly diabetic retinopathy, continue to significantly impact vision and remain a leading cause of vision loss in working-aged adults. Identifying specific genetic risk factors for ischemic-driven pathways that increase susceptibility to developing diabetic retinopathy is a priority to allow development of accurate risk assessment algorithms, employ earlier intervention, and design novel treatment strategies to reduce the associated visual complications. Single nucleotide polymorphisms (SNPs) in the VEGF gene have been shown to influence the expression of the VEGF protein. Several studies suggest that SNPs in the VEGF gene mediate genetic predisposition to diabetic retinopathy. In addition, alterations in the vitreous proteome, including carbonic anhydrase mediated vascular permeability, have been found to be associated with sight-threatening proliferative diabetic retinopathy and macular edema. Inhibition of these factors could provide new therapeutic opportunities for the treatment of diabetic retinopathy.     

Tonicity response element binding protein associated with neuronal cell death in the experimental diabetic retinopathy

AIM:To studythe contribution of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death of diabetic retinopathy (DR).METHODS:Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received vehicle (phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of TonEBP and aldose reductase (AR) were examined.RESULTS:The TonEBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)-positive signals co-localized with TonEBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION:The present data show that AR and TonEBP are upregulated in the DR and TonEBP may contribute to apoptosis of RGC in the DR.     

Inhibitory effects of bucillamine on increased blood-retinal barrier permeability in streptozotocin-induced diabetic rats

PURPOSE: To investigate the effect of bucillamine for prevention of increasing blood-retinal barrier (BRB) permeability in streptozotocin (STZ)-induced diabetic rats. METHODS: The groups included control and STZ-induced diabetic rats treated with or without bucillamine. Six months after intervention, the concentrations of reduced and oxidative glutathione (GSH and GSSG) in the retina were measured biochemically. In addition, vitreous fluorescein, which leaks from the vessels after intravenous injection of fluorescein sodium, was measured to evaluate BRB permeability. To evaluate the scavenging ability against the reactive oxygen species (ROS) in vitro, the second-order rate constant for the reaction of bucillamine with ROS was estimated from the kinetics based on the rate constant for the reaction of ROS. RESULTS: The BRB permeability was significantly higher (p = 0.01) in diabetic rats not treated with bucillamine, and bucillamine inhibited the BRB permeability. The GSH concentration and the GSH/GSSG ratio in the retinas decreased in diabetic rats not treated with bucillamine; bucillamine inhibited the decrease of the GSH concentrations. The ROS scavenging activity of bucillamine was similar with that of GSH. CONCLUSIONS: In diabetic retinas, oxidative stress might increase, which may be one of the causes of BRB breakdown. The antioxidant effects of bucillamine might take part in inhibition of increased permeability of the BRB in diabetes.     

Intravitreal bevacizumab in persistent retinopathy secondary to malignant hypertension

PurposeTo evaluate the efficacy and safety of intravitreal bevacizumab (IVB) injection in persistent retinopathy secondary to malignant hypertension (MHT).Patients and methodsSingle IVB injection of 1.25 mg/0.05 ml in 12 cases with persistent retinopathy secondary to MHT more than one month after control of MHT with pre and post injection evaluation of best corrected visual acuity (BCVA) and anatomical outcome up to sixth month and postinjection complications were evaluated.ResultsProgressive reductions in retinal hemorrhages, exudates, cotton-wool spots, and macular star were documented by photography, angiography, and central macular thickness (CMT) measured by optical coherence tomography (OCT) imaging. Decreased macular edema was the most common finding. Improvement or stabilization of visual acuity was noted in all cases.ConclusionsIn addition to proper medical management of MHT, IVB injection is an effective and safe approach to treat persistent retinopathy associated with MHT.     

Radiation Retinopathy Caused by Low Dose Irradiation and Antithyroid Drug-Induced Systemic Vasculitis

Background We report on a patient with Graves disease with radiation retinopathy caused by low-dose irradiation and antithyroid drug-induced antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis.Case A 38-year-old woman with Graves disease presented with bilateral blurred vision, microaneurysms, telangiectasia, and macular edema. The patient was examined by ophthalmoscopy and fluorescein angiography, and radiation retinopathy was diagnosed.Observations The patient had been treated with low-dose irradiation for her Graves ophthalmopathy a few years earlier. She also had ANCA-positive vasculitis induced by the antithyroid drug (propylthiouracil, PTU) that had been prescribed for her at that time. Because of multiple avascular areas on both retinas, she was treated by intensive retinal photocoagulation to control progressive retinopathy.Conclusions The radiation doses used to treat Graves disease ophthalmopathy are low. Nevertheless, there is still a risk of radiation retinopathy developing in patients with PTU-induced ANCA-positive vasculitis. Jpn J Ophthalmol 2005;49:261–263 © Japanese Ophthalmological Society 2005