促红细胞生成素在视网膜新生血管形成中的作用

促红细胞生成素（EPO）不仅为造血细胞因子，还具有血管生成素的活性，EPO／EPOR系统在体内组织中广泛表达，并参与体内众多生理和病理性血管生成过程。EPO在视网膜新生血管形成中起重要的作用，有望成为预防和治疗缺血性视网膜病变中新生血管化的全新的干预靶点，就EPO在视网膜新生血管形成中的作用进行综述。     

Photoreceptor cells and RPE contribute to the development of diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of blindness. It has long been regarded as vascular disease, but work in the past years has shown abnormalities also in the neural retina. Unfortunately, research on the vascular and neural abnormalities have remained largely separate, instead of being integrated into a comprehensive view of DR that includes both the neural and vascular components. Recent evidence suggests that the most predominant neural cell in the retina (photoreceptors) and the adjacent retinal pigment epithelium (RPE) play an important role in the development of vascular lesions characteristic of DR. This review summarizes evidence that the outer retina is altered in diabetes, and that photoreceptors and RPE contribute to retinal vascular alterations in the early stages of the retinopathy. The possible molecular mechanisms by which cells of the outer retina might contribute to retinal vascular damage in diabetes also are discussed. Diabetes-induced alterations in the outer retina represent a novel therapeutic target to inhibit DR.     

Experimental venous thrombosis: preretinal PO2 before and after photocoagulation

Experimental occlusion of a retinal vein leads to retinopathy in the affected drainage area. In some cases the formation of ischemic regions, where the retina is completely destroyed, is typical for the development of this retinopathy. Laser photocoagulation restores the physiological preretinal oxygen pressure in these hypoxic regions. It is possible that the rise in O2 pressure which has been observed is caused by destruction of pigment epithelium and the photoreceptor layer, as oxygen diffuses freely from the choroid to the inner retina without being consumed by the outer layers.     

Alternative pathways in the development of diabetic retinopathy: the renin-angiotensin and kallikrein-kinin systems

Diabetic retinopathy is a common complication of both type 1 and type 2 diabetes and is the leading cause of blindness in people of working age. Current treatment strategies are mostly limited to laser photocoagulation, which restricts proliferative retinopathic changes but also causes irreversible damage to the retina. This review examines two important pathways involved in regulating vascular function and their role in the development of diabetic retinopathy. One, the renin-angiotensin system, is well known and has established angiogenic effects on the retina that increase in diabetic retinopathy. The other, the kallikrein-kinin system, has recently been found to be important in the development of diabetic retinal complications. This review describes the components of the two signalling networks, examines the current animal model studies investigating the role of these pathways in diabetic retinopathy and reviews the clinical studies that have been undertaken examining systemic inhibition of different points in these pathways. These systems are promising targets for therapies aimed at inhibiting the development of diabetic retinopathy and in the future, combination therapies that take advantage of both pathways might result in new treatment options for this debilitating complication of diabetes.     

Electrophysiology in the investigation of acquired retinal disorders

Electrophysiological research on acquired retinal disorders, both common and rare, is reviewed. Age is a major factor influencing electroretinogram (ERG) and electro-oculogram (EOG) findings. Bipolar or Müller cell death in the aging retina could account for much of the amplitude decline that is observed with age. In diabetic retinopathy, the oscillatory potentials can monitor the progression of the disease and indicate neuronal alterations rather than diabetic angiopathy of the retina. Human ERG studies on glaucoma concentrated on ERG measures that are dominated by inner retinal contributions. It has been shown that the pattern ERG can serve as a predictor of ocular hypertension's progression to glaucoma. In retinal disorders caused by endogenous intoxication, such as hepatic retinopathy, or exogenous intoxication from chronic lead exposure, ERG changes give an objective measure of the damage and allow to study the pathophysiological mechanisms that are involved. Inflammations of the choroid and the retina affect the standard ERG when they are diffuse. In central serous chorioretinopathy, functional disturbances can be revealed not only in the photoreceptors but also in the middle and inner retinal layers with the use of focal stimuli. Choroidal melanoma leads to large reductions of the EOG light peak-to-dark trough ratio through its influence on the transepithelial potential of the retinal pigment epithelium (RPE). In cancer-associated retinopathy, both the rod and cone ERGs are reduced. However, selective cone dysfunction has been described. In melanoma-associated retinopathy, the long flash ERG may reveal a specific pathophysiological mechanism, namely the affection of the ON-pathway with preservation of the OFF-pathway. ERG measurements can reveal vitamin A deficiency and are altered in cases with a mutation in the gene for the retinol binding protein in which other organs are not affected. Photochemical damage to the retina from light emission by the operating microscope can be assessed by electrophysiological methods.     

Paraneoplastic Vitelliform Retinopathy: Clinicopathologic Correlation and Review of the Literature

Traditionally, the paraneoplastic retinopathies have been classified into two groups: melanoma-associated retinopathy (MAR) and cancer-associated retinopathy. MAR occurs in individuals with metastatic cutaneous or uveal melanoma and is characterized by nyctalopia, photopsias, and variable vision loss. In most cases, the fundus is essentially normal in appearance. More recently, there have been multiple reports of a MAR-like retinopathy with associated detachments of the retinal pigment epithelium and neurosensory retina. Such a clinical presentation has been termed paraneoplastic vitelliform retinopathy. We describe an 80-year-old man with metastatic cutaneous melanoma who developed paraneoplastic vitelliform retinopathy. For the first time, histopathology from enucleation specimens provides a clinicopathologic disease correlation with focal abnormalities in the inner nuclear and outer plexiform layers.     

Effect of partial cryoablation on retinopathy of prematurity.

Cryotherapy has been shown to be an effective treatment for retinopathy of prematurity stage 3. It is said to reduce the unfavourable outcome of the disease by 50%. The accepted method of therapy includes ablation of the whole avascular retina from the ridge to the ora serrata. This is achieved by two to three rows of cryoapplications. When 360 degrees cryo treatment is performed, it requires 52 cryo applications. We present our method of cryotherapy which involves only one row of cryoapplications in the avascular retina anterior to the fibrovascular ridge. An average of 25-30 cryoapplications was required for a 360 degrees treatment. The anatomical results in 23 babies are presented. Complete regression of active retinopathy was found in all.     

蛋白质组学在糖尿病视网膜病变中的应用

糖尿病视网膜病变是眼科常见的致盲眼病之一,其病理过程涉及视网膜、玻璃体等许多眼部组织,并引起相应部位甚至血清蛋白质表达水平及成分的变化。蛋白质组学作为一项从整体角度分析蛋白质变化的新兴科学,已逐渐被应用于糖尿病视网膜病变的研究,本文就蛋白质组学及其在糖尿病视网膜病变研究中的应用做一综述。     

Retinal neurodegeneration: early pathology in diabetes

Normal vision depends on the normal function of retinal neurons, so vision loss in diabetes must ultimately be explained in terms of altered neuronal function. However to date relatively little attention has been paid to the impact of diabetes on the neural retina. Instead, the focus of most research has been primarily on retinal vascular changes, with the assumption that they cause altered neuronal function and consequently vision loss. An increasing body of evidence suggests that alterations in neuronal function and viability may contribute to the pathogenic mechanisms of diabetic retinopathy beginning shortly after the onset of diabetes. This view arises from neurophysiological, psychometric, histopathological and biochemical observations in humans and experimental animals. The collective evidence from past and recent studies supports the hypothesis that neurodegeneration, together with functional changes in the vasculature, is an important component of diabetic retinopathy. The authors invite other investigators to include the neural retina as a component of their studies so that the pathogenesis of diabetic retinopathy can be understood more clearly.     

Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome.

BACKGROUND: The mechanism leading to visual loss in paraneoplastic retinopathy is not known. An autoimmune process has been imputed based on immunologic investigations of several patients and by analogy to certain other paraneoplastic syndromes. METHODS: Two patients with documented small cell carcinoma of the lung who had clinical evidence of paraneoplastic retinopathy are described. Histopathologic examination of the retina from one patient and immunohistochemical staining of human retina with serum from control subjects and both patients were performed. RESULTS: Electroretinograms demonstrated dysfunction of photoreceptors in both patients, with predominant loss of rod function in one patient. Post mortem examination showed patchy loss of photoreceptors of the extramacular retina and relative sparing of cones, findings consistent with the clinical and electrophysiologic test results. Serum from both patients stained the retina in an identical manner, with restriction of the stain to the outer retina. Stain was present over the outer plexiform layer, the outer nuclear layer, and the inner and outer segments of most photoreceptors. A sharp demarcation was present between those areas that did and did not stain. All rod inner and outer segments appeared to stain, and many cone inner segments were not stained. Immunologic tests obtained elsewhere did not show serum antibody to the 23 kD protein. CONCLUSION: These findings support the concept of an autoimmune pathogenesis by showing selectivity of the immune response and correlation between the apparent target of the immune response and the clinical and pathologic findings. The mechanism by which cell loss occurs in the retina is not answered by this study. The absence of antibody to the 23 kD protein does not exclude the diagnosis of paraneoplastic retinopathy.     

Presumed exudative retinal detachment after cryotherapy in retinopathy of prematurity.

Cryotherapy of the peripheral avascular retina in selected cases of retinopathy of prematurity has been shown to reduce the incidence of posterior retinal detachment, retinal fold involving the macula, and retrolental tissue. Although exudative retinal detachments have been described after cryotherapy during scleral buckling procedures, to our knowledge, this observation has not been reported after cryotherapy in retinopathy of prematurity. We describe such a case.     

细胞因子与糖尿病视网膜病变的研究进展

糖尿病视网膜病变（DR）是一种发生进行性视力损害的糖尿病（DM）并发症,其特征是毛细血管闭锁、微循环障碍和局部缺血性视网膜新生血管形成,其确切的发病机制尚不清楚。最近有研究认为DR可能与视网膜毛细血管炎症反应有关。由于细胞因子能引起炎症反应和黏附分子表达,因此细胞因子增加单核细胞和内皮细胞黏附的过程被认为是DR发生发展过程中的关键事件。就血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）、碱性成纤维细胞生长因子（bFGF）等多种细胞因子在DR中的作用进行综述。     

Retinal oxygenation and laser treatment in patients with diabetic retinopathy.

The oxygen tension in the preretinal vitreous cavity was measured in human patients undergoing vitreous operations for proliferative diabetic retinopathy. The oxygen tension was significantly higher (P = .004) over areas of retina that had been treated with panretinal photocoagulation than it was over untreated areas in the same retina. This confirmed previous results in animals that showed that panretinal photocoagulation increases the inner retinal oxygen tension. We concluded that panretinal photocoagulation improves the oxygen supply to the inner retina and thereby minimizes the influence of retinal ischemia in diabetic retinopathy.     

Pathologic features of cytomegalovirus retinopathy after treatment with the antiviral agent ganciclovir

Ganciclovir is a new antiviral compound (also called BW B759U, DHPG, BIOLF-62, and 2'NDG) that has been used for the treatment of cytomegalovirus (CMV) retinopathy in immunocompromised patients (bone marrow recipients or acquired immune deficiency syndrome [AIDS] victims). The authors studied the eyes of three AIDS patients with CMV retinopathy who died while receiving ganciclovir chemotherapy. Gross, microscopic, and ultrastructural studies of these cases showed varying degrees of retinal scarring and active CMV lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In situ hybridization using a cloned complementary DNA (cDNA) probe of human CMV corroborated the immunocytologic localization of the virus. Ultrastructural studies showed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. The cytoplasmic electron-dense membrane-bound bodies that have characterized untreated cases of CMV retinopathy were absent in the treated cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostatic chemotherapeutic agent.     

On the pathogenesis of diabetic retinopathy. A 1990 update

Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane.     

RetCam Ⅱ下小儿眼底病变的特征观察

目的 观察广域数字化视网膜摄像系统(RetCamⅡ)检查所见的小儿眼底病变的图像特征和发病情况,探讨其在小儿眼底病变诊断中的临床价值,为早期干预、减少儿童盲和低视力提供科学依据.方法 横断面研究.湖南省儿童医院眼科在2009年9月至2010年12月间经RetCamⅡ检查的患儿4574例.表麻下用复方托吡卡胺滴眼液散瞳后采用RetCamⅡ的130°镜头进行双眼全面眼底照相检查,将眼底图像存档并分析,对病例进行计数并求百分比.结果 4574例小儿中筛查出667例患眼底病变,筛查阳性率为14.58％.其中早产儿视网膜病变(ROP)412例(占早产儿的12.05％),视网膜出血151例,家族性渗出性视网膜病变7例,视网膜发育不良6例,视网膜渗出改变62例,白内障3例,牵牛花综合征8例,视网膜母细胞瘤7例,视神经萎缩3例,黄斑病变7例,真菌性视网膜炎1例.结论 RetCamⅡ可真实客观地观察到小儿眼底病变的特征并追踪其变化及疗效,具有很好的临床应用价值,加强小儿眼底病变的早期筛查与干预是防治儿童盲与低视力的关键.     

视网膜电图PhNR和OPs在非增生型DR中的变化特点

目的观察非增生型糖尿病视网膜病变（DR）中视网膜电图PhNR和OPs的变化特点,比较OPs、PhNR指标在早期诊断及评估视网膜功能的敏感性和特异性。方法选取经间接检眼镜、荧光素眼底血管造影（FFA）确诊的DR患者30例（30眼）,同时选取与其性别、年龄相匹配的正常对照25例（25眼）作为对照组。2组均进行视力、闪光视网膜电图（F-ERG）、FFA检查。比较2组PhNR振幅、OPs振幅及ERG其他参数指标,并探讨不同DR分级与PhNR振幅、OPs振幅的变化关系。结果在OPs指标中,DRⅠ~Ⅳ级OPs振幅与正常值比较差异均有统计学意义（P〈0.05）,PhNR指标显示,DRⅠ级PhNR振幅与正常值比较,差异无统计学意义（P〉0.05）,DRⅡ~Ⅳ级与正常组比较,差异均有统计学意义（P〈0.05）。在比较各参数ROC下面积（AUC）中,OPs指标的AUC最高,为0.866;其次是PhNR指标,AUC为0.754。OPs诊断NPDR的敏感性和特异性分别为63.6%和80%,而PhNR的敏感性和特异性分别为54.5%和73.3%。结论DR在病变初期即出现血液循环性改变、神经细胞功能障碍,表现为PhNR振幅和OPs振幅均明显降低。OPs指标在DR的早期诊断及评估视网膜功能方面敏感性和特异性更高。     

An endothelin type A receptor antagonist reverses upregulated VEGF and ICAM-1 levels in streptozotocin-induced diabetic rat retina

Diabetic retinopathy, a cause of blindness, is often associated with the upregulation of vascular endothelial growth factor (VEGF) in the retina. Recently, leukocyte adhesion (leukostasis) is claimed for the occlusion of retinal capillary vascularity, which ultimately assists in the progression of diabetic retinopathy. In addition, intercellular adhesion molecule-1 (ICAM-1), a representative factor for leukostasis, is increased in diabetic retina. Endothelin (ET)-1, a potent vasoconstrictor peptide, is closely linked to the pathogenesis of diabetic retinopathy. Different therapeutic interventions concerning VEGF have already been proposed to prevent diabetic retinopathy. However, no study has yet reported concerning the effects of ET-1 receptor antagonist on the upregulated VEGF and ICAM-1 in morphologically intact diabetic retina. The current study investigated the effect of ET(A) receptor antagonist (TA-0201; 1 mg kg(-1) day(-1)) on the expressions of VEGF and ICAM-1 in rat diabetic retina. Diabetes was induced by intraperitoneal injection of streptozotocin (70 mg/kg) in Sprague-Dawley rats, whereas control rats (Cont) received only citrate buffer. After 1 week, the streptozotocin-administered rats were randomly divided into two groups: ET(A) receptor antagonist-treated group (DM+TA-0201) and saline-treated group (DM+vehicle). After the treatment for 4 weeks, the retina was removed from the eyeball. In DM+vehicle group, the VEGF expression of retina was significantly increased (33.5 pg/mg) in comparison with that in the Cont group (25.1 pg/mg), and the upregulation of VEGF was reversed in DM+TA-0201 group (26.9 pg/mg), a phenomenon consistent with the change in VEGF mRNA levels. The expression of retinal ICAM-1 was increased in DM+vehicle group (55.1 pg/mg) compared with Cont group (43.8 pg/mg), and ET antagonism completely blocked this increase (43.8 pg/mg). Moreover, an increased leukostasis by 3.3-fold in DM+vehicle retina was returned to the control level by ET antagonism. In the current study, there was no obvious retinal morphological alteration from both the hematoxylin and eosin staining and the FITC-dextran angiography. Thus, ET(A) receptor antagonist might be useful in preventing the progression of diabetic retinopathy, as evidenced by suppressing the increase in VEGF and ICAM-1 levels as well as leukostasis in morphologically intact diabetic retina.     

Upregulation of glucose-dependent insulinotropic polypeptide and its receptor in the retina of streptozotocin-induced diabetic rats

The pathology of diabetic retinopathy includes dilatation and beading of retinal vessels, and vascular sheathing. To gain a better understanding of the molecular events leading to diabetic retinopathy, we investigated disease-specific gene responses by screening differential expression using cDNA microarray. Male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ, 50 mg/kg) or the control buffer and were maintained for 6 weeks. Total RNA extracted from the retinas of both groups was used for cDNA microarray analysis. Signals from all the spots representing hybridized DNA were quantified and compared between the normal and diabetic rat retinas. Among 1176 genes analyzed, the retinal expression of glucose-dependent insulinotropic polypeptide (GIP) was found to increase in STZ-induced diabetic rats compared to controls. GIP is a secreted protein, known to be released from the small intestine, which potentiates glucose-induced insulin secretion from the pancreas. However, the expression of GIP and its receptor (GIPR) has not been previously noted in the rat retina. To further validate the expression of GIP in the rat retina and to determine its possible role in the development of early diabetic retinopathy, we investigated its expression by RT-PCR, Northern blotting, and immunohistochemistry in normal and diabetic rat retinas. GIP mRNA and protein are not only expressed in the rat retina, but their levels are greater in the diabetic rat as compared to controls. And GIPR expression was also upregulated in the retinas of STZ-induced diabetic rats. We here demonstrate for the first time the expression of GIP and GIPR in the rat retina. And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina.     

糖尿病视网膜病变多点扫描激光治疗的研究现状

糖尿病视网膜病变(diabetic retinopathy,DR)是糖代谢异常导致的眼部严重微血管并发症,是工作人群中首位致盲性眼病。尽管现在有多种方法可以有效治疗DR,如玻璃体腔注药术、光动力疗法(photodynamic therapy,PDT)、玻璃体切割术(pars plana vitrectomy,PPV)等,但激光光凝视网膜仍是目前DR治疗的首选方法。但近年来随着激光技术的发展,传统激光中的单点模式已不能满足临床需要,已逐渐被更安全、更有效、并发症少的多点扫描激光替代。我们就DR的多点扫描激光治疗现状作一综述。