MNU诱导的视网膜光感受器细胞损伤过程中视网膜VEGF表达的变化

目的： 探讨N-甲基-N-亚硝脲（MNU）诱导的大鼠视网膜光感受器细胞损伤过程中视网膜血管内皮生长因子（VEGF）的表达变化。方法: 50 d龄雌性SD大鼠55只,随机分5组,正常组和造模组（分4个组）,造模组40 mg/kg MNU单次腹腔注射,在注射后1 d、3 d、7 d和10 d取眼球立即分离视网膜以提取总RNA,通过RT-PCR检测VEGF mRNA的表达情况;摘取眼球进行冰冻切片,免疫荧光技术检测VEGF蛋白质在视网膜中的表达以及分布的变化。结果: RT-PCR检测结果表明,与正常对照组比较,MNU造模后1 d,VEGF mRNA的表达均较强,3 d VEGF表达最高,P＜0.01;7 d和10 d恢复正常,无明显差异,P＞0.05。免疫荧光检测结果显示,VEGF蛋白质表达与RT-PCR检测结果基本一致,VEGF蛋白质在视网膜各层均有表达,造模后1 d和3 d,外核层损伤较重,外核层VEGF的表达明显增强。结论: MNU诱导的视网膜光感受器细胞损伤可使VEGF的表达增强,提示VEGF可能参与MNU诱导的视网膜光感受器细胞的损伤修复。     

杞菊地黄汤防治MNU诱导大鼠视网膜变性的早期效应

目的:观察杞菊地黄汤在N-甲基-N-亚硝脲(MNU)诱导的SD大鼠视网膜变性早期的拮抗效应。 方法:生后46 d的雌性SD大鼠30只随机分为3组(n=10)：药物组以杞菊地黄汤灌胃，正常组和模型组以等量蒸馏水灌胃，每日1次，连续4 d。用药后第5 d，药物组和模型组大鼠皮下注射MNU 40 mg/kg，正常组皮下注射等量生理盐水做对照。注射后12 h，处死大鼠，每组大鼠的左眼（10眼）用于透射电镜观察；右眼（10眼）用于苏木素-伊红(hematoxylin eosin,HE)染色观察并测量分析视网膜全层及外核层厚度，部分眼球行TUNEL法染色并计算细胞凋亡百分率。 结果:光镜下各组大鼠视网膜组织学未见明显改变，视网膜全层及外核层厚度组间比较均无显著差异（P>0.05）。TUNEL法染色见模型组和药物组外核层存在细胞凋亡，正常组未见。电镜下正常组和药物组光感受器细胞大小和核染色质分布均匀；模型组光感受器细胞开始变小，核染色质开始浓缩, 外节膜盘疏松，膜型不完整。 结论:杞菊地黄汤通过抑制细胞凋亡等选择性拮抗MNU对大鼠视网膜光感受器细胞的早期损伤。     

银杏苦内酯B对N-甲基-N-亚硝脲诱导的大鼠视网膜细胞凋亡的抑制作用

目的: 探讨银杏苦内酯B(GB)对N-甲基-N-亚硝脲(MNU)诱导的大鼠视网膜变性的影响及其机制。方法: 建立大鼠视网膜变性模型,应用TUNEL法检测光感受器细胞凋亡,RT-PCR法和免疫组织化学法分别检测MNU作用后不同时间大鼠视网膜中bcl-2和bax mRNA和蛋白的表达。结果: GB治疗组外核层细胞凋亡指数显著低于模型组(P<0.01)。MNU作用后12 h、1 d、2 d、3 d和5 d,bcl-2/bax mRNA模型组为0.36、0.15、0.29、0.42和0.64,GB治疗组为0.98、0.92、0.53、0.45和0.68,显著高于模型组(P<0.01)。GB治疗组Bcl-2蛋白在MNU给药后1 d表达最强,2 d阳性表达下降,3 d后阳性表达消失,模型组未见视网膜Bcl-2阳性表达;GB治疗组Bax蛋白表达显著低于模型组(P<0.01)。结论: 银杏苦内酯B能抑制MNU诱导的视网膜光感受器细胞凋亡,可能与上调Bcl-2的表达量,提高Bcl-2/Bax比值有关。     

不同MNU剂量诱导大鼠视网膜光感受器细胞损伤的视网膜电图和病理形态改变

目的： 探讨不同剂量N-甲基-N-亚硝脲（MNU）诱导的大鼠视网膜光感受器细胞损伤动物模型的眼电图和病理形态改变，寻找最适的MNU剂量。方法: 50 d龄雌性SD大鼠150只，随机分6组(每组25只大鼠)，即30 mg/kg、35 mg/kg、40 mg/kg、45 mg/kg和50 mg/kg MNU造模组和正常对照组，在造模后12 h、1 d、3 d、7 d和10 d测定大鼠的眼电生理，并取眼球进行病理检查。结果: 大鼠眼电生理结果显示，与正常组比较，30 mg/kg和35 mg/kg MNU组在各个时点对a波潜伏期和b波潜伏期的影响变化不大（P＞0.05）；a波振幅和b波振幅在第1、3 d下降较为明显(P＜0.05或 P＜0.01）。30 mg/kg和35 mg/kg MNU组在不同的时点:a波潜伏期、b波潜伏期、a波振幅和b波振幅明显高于40 mg/kg、45 mg/kg和50 mg/kg MNU组(P＜0.05或 P＜0.01）。45 mg/kg和50 mg/kg MNU组在不同的时点绝大多数呈现熄灭型电生理的表现。病理结果显示，在不同的时点，30 mg/kg和35 mg/kg MNU对大鼠视网膜光感受器细胞的损伤程度较轻，明显低于40 mg/kg、45 mg/kg和50 mg/kg MNU对大鼠视网膜外核层的损伤(P＜0.05或 P＜0.01）。损害程度为50 mg/kg＞45 mg/kg＞40 mg/kg。结论: 对大鼠视网膜光感受器细胞的病理和功能损害， 30 mg/kg和35 mg/kg MNU组损害较轻，40 mg/kg、45 mg/kg和50 mg/kg MNU组损害较重，40 mg/kg MNU是引起大鼠视网膜光感受器细胞最大损害的最低剂量。     

碘酸钠诱导大鼠视网膜损伤的病理改变和SOD、CAT的变化

目的: 探讨不同剂量碘酸钠诱导大鼠视网膜损伤过程中的病理形态改变及抗氧化系统中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的改变。方法: SD大鼠80只,随机分为4组(每组20只),即40 mg/kg、50 mg/kg、60 mg/kg碘酸钠造模组和正常对照组。在造模后第1、4、7、14 d取大鼠右眼进行病理检查;取左眼视网膜,检测SOD和CAT的活性。结果: 病理结果显示,与对照组比较,第1 d,40 mg/kg和50 mg/kg碘酸钠造模组视网膜各层未见损伤,60 mg/kg碘酸钠造模组出现视网膜色素上皮层损伤、外核层细胞排列紊乱;第4、7、14 d,各剂量组均出现明显损伤,且损伤程度比第1 d和对照组明显加重,呈现外核层细胞波浪状改变和外核层厚度减少(P＜0.05或P＜0.01)。生化检测结果显示,与对照组比较,第1、4 d,60 mg/kg碘酸钠造模组视网膜组织SOD、CAT的活性均显著下降(P＜0.05);第7、14 d,各剂量组视网膜SOD、CAT活性均呈明显下降趋势(P＜0.05或P＜0.01)。结论: 40 mg/kg、50 mg/kg和60 mg/kg的碘酸钠均可导致大鼠视网膜色素上皮层和外核层细胞损伤,并使大鼠视网膜抗氧化系统受损。碘酸钠用量越大,视网膜细胞损伤出现时间越早、程度越重。     

N-甲基-N-亚硝脲诱导的大鼠视网膜感光细胞损伤模型中Müller细胞增殖和细胞因子分泌的变化

目的:建立N-甲基-N-亚硝脲(N-methyl-N nitrosourea,MNU)损伤视网膜的模型,研究视网膜神经元凋亡对Müller细胞生物学特性的影响及神经营养因子的表达变化。方法:腹腔注射MNU建立视网膜损伤模型,免疫荧光染色方法研究感光细胞缺失对Müller细胞的生物学特性的影响,并检测主要神经营养因子表达的变化。结果:TUNEL法显示,腹腔注射MNU后2 d,视网膜外核层细胞凋亡现象明显。核增殖抗原(PCNA)及细胞周期素CyclinD_1的表达明显增高。与此同时,Müller细胞也开始表达神经干细胞抗原巢蛋白(nestin);RT-PCR显示胰岛素样生长因子(IGF),碱性成纤维细胞生长因子(bFGF)和肝细胞生长因子(HGF)mRNA的表达均升高。结论:在视网膜受到损伤时,Müller细胞增殖、去分化呈现出干细胞的特性。而视网膜中IGF、bFGF和HGF等细胞因子的表达明显增高,提示视网膜损伤后可能通过大量分泌细胞生长因子,促进Müller细胞的增殖。     

青光眼致病基因OPTN在大鼠光感受器细胞内的表达

目的观察OPTN在大鼠视网膜光感受器细胞内的表达及定位,探讨OPTN和NRL(neural retina leucine zipper)两蛋白相互的作用。方法制备正常Wistar大鼠的视网膜冷冻切片,用抗OPTN抗体、抗NRL抗体和抗CRX抗体分别进行多重免疫荧光染色。结果在外丛状层(OPL)、外核层(ONL)、光感受器细胞内节(IS)、神经节细胞层、内丛状层(IPL)和内核层(INL)中均观察到抗OPTN抗体不同强度的荧光信号。光感受器细胞内的荧光信号主要在细胞质内,而细胞核内未见染色,且具有视锥细胞特征的细胞未被抗OPTN抗体染色。结论 Optn(OPTN的大鼠同源基因)在除视锥细胞以外的光感受器细胞高表达。     

菩人丹超微粉对糖尿病大鼠视网膜神经细胞凋亡及相关基因表达的影响

目的: 探讨菩人丹超微粉(PRD)对糖尿病大鼠视网膜神经细胞凋亡及相关基因表达的影响。方法: 36只Wistar大鼠随机分为3组,正常对照组、糖尿病模型组和PRD治疗组,每组12只。糖尿病模型组和PRD治疗组大鼠均采用链脲佐菌素连续腹腔注射建立2型糖尿病大鼠模型。模型成功建立后,PRD治疗组大鼠给予PRD灌胃3个月。采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测大鼠视网膜神经细胞的凋亡;SP免疫组织化学染色法检测视网膜B细胞白血病/淋巴瘤相关抗原2(Bcl-2)、B细胞白血病/淋巴瘤相关抗原相关X蛋白(bax)和半胱氨酸天冬氨酸蛋白酶3(caspase-3)蛋白的表达;逆转录聚合酶链反应(RT-PCR)检测bcl-2、bax和caspase-3 mRNA的表达。结果: 糖尿病模型组与正常对照组比较,大鼠视网膜神经细胞凋亡指数、Bax、 caspase-3蛋白及mRNA的表达均明显升高(P＜0.01),Bcl-2蛋白及mRNA的表达、Bcl-2/Bax比值显著降低(P＜0.01);PRD治疗组与模型组比较,大鼠视网膜神经细胞凋亡指数、bax、caspase-3蛋白及mRNA的表达均明显降低,Bcl-2 蛋白及mRNA的表达、Bcl-2/Bax比值显著升高(P＜0.01)。结论: PRD可通过上调Bcl-2的表达及下调Bax及caspase-3的表达,抑制糖尿病大鼠视网膜神经细胞的凋亡,发挥对糖尿病视网膜的保护作用。     

硫酸软骨素酶联合脂肪间充质干细胞治疗大鼠视网膜变性北大核心

背景:有研究发现硫酸软骨素酶降解硫酸软骨素蛋白多糖能够促使视网膜上Müller细胞的移行,但硫酸软骨素酶降解硫酸软骨素蛋白多糖是否能促进脂肪间充质干细胞在视网膜变性大鼠视网膜的移行尚不明确。目的:探讨硫酸软骨素酶降解硫酸软骨素蛋白多糖对脂肪间充质干细胞治疗大鼠视网膜变性的影响。方法:分离并培养人脂肪间充质干细胞,建立视网膜变性大鼠模型,向视网膜变性大鼠视网膜下腔注射脂肪间充质干细胞+硫酸软骨素酶,观察移植后大鼠脂肪间充质干细胞迁移率和视网膜细胞凋亡情况。结果与结论:人脂肪间充质干细胞能够成功培养,Brd U对人脂肪间充质干细胞的标记率达90.0%以上。建模后7 d,视网膜外核层塌陷,光感受器细胞大量外节迸解,外核层贴附在Bruch’s膜上,视网膜呈拱桥样,中央视网膜和外周视网膜均受到损伤;正常大鼠视网膜各层清晰,光感受器细胞排列规律,视网膜色素上皮层完整。脂肪间充质干细胞+硫酸软骨素酶组脂肪间充质干细胞迁移率高于脂肪间充质干细胞组,且2组视网膜细胞凋亡率比较差异无显著性意义。表明硫酸软骨素酶降解硫酸软骨素蛋白多糖可提高人脂肪间充质干细胞在视网膜上的迁移能力。     

氧诱导视网膜新生血管模型中基质细胞衍生因子1的表达及机制研究

目的: 观察基质细胞衍生因子1(SDF-1)在氧诱导视网膜新生血管(OIR)模型中的表达情况,并初步研究其在OIR模型中的促新生血管生长机制。方法: 30只C57BL/6J新生小鼠随机分为2组。其中15只小鼠置于氧浓度为75%的容器内饲养5 d,再转移至正常空气下饲养5 d,作为高氧诱导组;另15只小鼠一直在正常空气中饲养,作为正常对照组。免疫组织化学方法检测视网膜SDF-1、CD14蛋白的定位及含量,real-time PCR法检测视网膜SDF-1 mRNA的表达。结果: 与正常对照组相比,高氧诱导组突破视网膜内界膜的内皮细胞核数目明显增多(P<0.01),血管分支减少,大血管扩张、迂曲。两组小鼠视网膜神经上皮均可见SDF-1和CD14阳性染色,但高氧诱导组的SDF-1和CD14含量明显高于正常对照组(均P<0.01)。并且视网膜SDF-1与CD14的蛋白含量存在正相关(r=0.898,P<0.01)。视网膜SDF-1 mRNA表达在高氧诱导组也明显高于正常对照组(P<0.01)。结论: OIR模型小鼠视网膜SDF-1表达增高,其促新生血管功能可能与CD14⁺细胞有关。     

Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal degeneration in neonatal mice

The morphologic response of neonatal mouse retina to the alkylating agent N -methyl- N -nitrosourea (MNU) was examined at different periods of retinal development. A dose of 60 mg/kg N -methyl- N -nitrosourea was injected intraperitoneally to neonatal C₅₇BL mice at 0, 3, 5, 8, 11, 14, 17, and 20 days of age and to C₃H mice at 0 days of age, and the retinas were examined sequentially. In the C₆₇BL mice, MNU evoked a time-dependent occurrence of retinal dysplasia and retinal degeneration. With MNU treatment at day 0 and day 3 (the stage of retinal cell proliferation), retinal dysplasia characterized by the progressive disorganization of neuroblasts, which led to the formation of rosettes, was found in the outer neuroblastic/nuclear layer above the normal pigment epithelial cells during days 8–20, but decreased at day 50. The rosettes were surrounded by photoreceptor segments and Muller cell processes, and by photoreceptor nuclei. The MNU response was related to retinal differentiation; following MNU treatment at day 5 or 8 (the stage of retinal cell differentiation) the cells were much less sensitive (i.e. no retinal response was found). However, with MNU treatment at days 11, 14, 17, and 20 (after cellular differentiation), retinal degeneration characterized by selective photoreceptor apoptosis was seen. These results suggest that there is a critical period for the time of MNU administration in the development of mouse retinal lesions. In C₃H ( rd/rd ) mice, MNU treatment at day 0 resulted in retinal degeneration with only slight rosette formation at the peripheral retina.     

Caspase-9抑制剂对RCS大鼠感光细胞凋亡抑制作用的研究

目的：采用Z-LEHD-FMK进行体内实验，观察caspase-9抑制剂对RCS大鼠感光细胞凋亡的抑制作用。方法：32只 18 d RCS大鼠随机分4组，检查ERG后随机选择一眼为实验眼给予玻璃体内注射Z-LEHD-FMK 4 μg，对侧眼给予4 μg 2%DMSO作对照。各组分别在术后2 d、7 d、12 d、17 d行ERG检查，然后摘取双眼球，石蜡切片行HE染色及感光细胞凋亡的TUNEL检测，透射电镜观察视网膜超微结构。结果：实验眼注药后 7 d ERG b波振幅达到最大(137.35±7.41)mV，17 d时b波振幅为(57.91±9.27)mV，对照眼7 d及以后各组ERG接近熄灭型；实验眼注药后12 d视网膜外颗粒层才开始出现凋亡阳性细胞，17 d更明显，对照眼强荧光的凋亡阳性细胞在术后7 d已经很明显；光镜下注药后17 d实验眼感光细胞外颗粒层细胞数尚保持有7-8层，对照眼仅余下2-4层细胞，视网膜厚度变薄；透射电镜下实验眼注药后17 d可见部分感光细胞胞核、核仁固缩，对照眼从术后 7 d 开始见感光细胞呈现凋亡改变。结论：Z-LEHD-FMK能够延缓RCS大鼠感光细胞凋亡，合适的caspases抑制剂在适宜的时机应用对视网膜感光细胞凋亡具有一定的抑制作用。     

Increased expression of ciliary neurotrophic factor receptor alpha mRNA in the ischemic rat retina

Using in situ hybridization, we investigated the expression of ciliary neurotrophic factor receptor ((CNTFRalpha) mRNA in the rat retina rendered ischemic by elevation of the intraocular pressure (IOP). The IOP was increased to 120 mmHg and maintained for 60 min. The rats were sacrificed on the day of reperfusion (DRP) 1, 3, 7, 14, and 28. In the normal retina, the signal for CNTFRalpha mRNA was present in retinal cells in the inner nuclear layer (INL) and in the ganglion cell layer (GCL). On DRP 1, numerous cells in the INL and GCL showed a CNTFRalpha mRNA signal. From DRP 3 onwards, CNTFRalpha mRNA appeared in photoreceptor cells located in the outer part of the outer nuclear layer. The signal in these cells increased up to DRP 14 and then decreased at DRP 28. Our findings suggest that cells expressing CNTFRalpha mRNA may resist the degenerative processes induced by ischemic insult in the rat retina.     

RCS变性大鼠感光细胞凋亡及其视网膜电图与caspase-9时空表达的关系研究

目的：研究caspase-9在英国皇家外科学院(RCS)变性大鼠视网膜的时空表达状况与其视网膜电图(ERG)以及感光细胞凋亡的关系，以探讨caspase-9在感光细胞凋亡中的作用。 方法： 不同日龄RCS变性大鼠，检查ERG后处死取视网膜行caspase-9的免疫组化、荧光活力分析、Western blotting及凋亡TUNEL检测。 结果： 15及20 d变性大鼠ERG b波潜伏期分别为(58.60±3.42)ms、(56.45±1.08)ms，振幅分别为(109.07±14.50)mV、(109.00±7.35)mV，两组间无显著性差异，25和30d组接近熄灭型。TUNEL阳性细胞只在变性大鼠的外颗粒层表达，25 d最明显。25 d后的变性大鼠感光细胞内节可见明显caspase-9阳性表达，其余各组未见表达。20 d caspase-9表现出最大活力［(10.98±0.13)nmol·g-1·min-1］。Western blotting分析显示caspase-9裂解条带在20 d时最明显，15 d组和对照组不表达。 结论： caspase-9的表达与视网膜感光细胞凋亡、视功能丧失存在时空一致性。     

Retinal degeneration induced in adult mice by a single intraperitoneal injection of N-ethyl-N-nitrosourea

Seven-week-old female BALB/c mice received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (50, 100, 200, 400, or 600 mg/kg), and retinal damage was evaluated after 7 days. Sequential morphological features of the retina and retinal apoptosis, as determined by the TUNEL assay, were analyzed 6, 12, 24, and 72 hr and 7 days after treatment with 600 mg/kg of ENU. Moreover, older mice (25 to 34 weeks of age) received an intraperitoneal injection of 600 mg/kg ENU and were sacrificed 7 days later. All animals were necropsied, and both eyes were examined histopathologically. Two of the 5 mice that received 600 mg/kg ENU died during the experimental period. Histopathologically, all mice that received 600 mg/kg of ENU experienced retinal degeneration characterized by the loss of photoreceptor cells (disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina within 7 days. One of 5 mice treated with 400 mg/kg ENU exhibited retinal damage that was restricted to the central retina. Older mice treated with 600 mg/kg ENU exhibited retinal damage that was similar to the retinal damage in younger mice. In the 600 mg/kg ENU-treated mice, TUNEL-positive photoreceptor cells peaked 72 hr after ENU treatment. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after treatment. In conclusion, ENU induces retinal degeneration in adult mice that is characterized by photoreceptor cell apoptosis.     

RCS大鼠感光细胞凋亡与 Fas蛋白表达

为了探讨遗传性视网膜变性时感光细胞凋亡及其基因调控机制 ,本研究对出生后 9、15、2 0、2 5、3 0、3 5、40、60 d的 RCS大鼠及同龄 SD大鼠各 4只的视网膜进行了 TU NEL 凋亡检测及 Fas蛋白免疫组织化学反应。结果表明 ,出生后 2 5～ 40 d,RCS大鼠视网膜外核层可见 TUNEL阳性的感光细胞核 ,TUNEL阳性细胞数到 3 5 d达高峰 ( P<0 .0 5 )。Fas蛋白免疫组织化学检测发现 ,RCS大鼠视网膜内核层在 15～ 40 d可见 Fas免疫阳性细胞 ,阳性细胞数以 2 5 d为最多 ( P<0 .0 5 ) ;外核层在 2 5 d也可见Fas蛋白免疫阳性反应 ,一直持续到 40 d;节细胞层在 15～ 40 d可见 Fas蛋白表达。到 60 d时则各层又都不见明显的 Fas蛋白阳性反应。本研究结果提示 ,在 RCS大鼠视网膜变性过程中 ,感光细胞发生凋亡 ,Fas蛋白高表达可能与感光细胞的凋亡有关     

Pigmentary degeneration indwed by N-methyl-N-nitrosourea and the fate of pigment epithelial cells in the rat retina

Pigmentary degeneration of the retina was induced by a single intraperitoneal Injection of 75mgkg of N-methyl-N-nitrosourea (MNU) In female Brown-Norway colored rats at 50 days of age, which were then observed at 24, 48 and 72 h and 7, 21,35 and 150 days after the treatment. MNU-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanlsm 24 h after the treatment, and the destruction was completed by day 7. During the photoreceptor cell degeneration, proliferation of Miller cells and infiltratlon of macrophages was prominent 72h and 21 days aRttr the treatment, respectively. Müller cell proliferation and macrophage infiltratbn corresponded to degenerative photo-receptor cell phagocytosis, and prollferating Müller cell processes responded to stabilize the damaged retina. Pigment epithelial cell detachment from the Bruch's membrane was seen 72 h after the treatment, and migration within all layers of the retina was seen at day 7 when photoreceptor Cells were lost. At 21, 35 and 150 days after the treatment, lack of photoreceptor cells and deposition of pigment epithelial cells within the retina but not in contact to vascular endothe-lial cells were characteristic. MNU-induced photoreceptor apoptosis followed by Miiller cell and macrophage reaction then pigment epithellal cells deposition withln the retina partially resembles retinitis pigmentosa in humans.     

Ultrastructural study on the photoreceptor layer in streptozotocin-induced diabetic rats

The aim of this research was to investigate the ultrastructure of the photoreceptor layer of diabetic male Wistar rat retina. Ten apparently healthy Wistar adult rats (aged 75 days) were used and divided into two groups: (1) control group and (2) diabetic group (injected intraperitoneally with streptozotocin 90 mg/kg). Samples were taken as small pieces from the retina near the optic disc and studied using a transmission electron microscope. Results showed that outer segments loss, scattered inner segments, and condense and pyknotic nuclei and karyolysis were obvious in diabetic group. The quantitative evaluations of different layers of photoreceptor cells showed that a significant decrease was observed in outer segments, inner segments, and outer nuclear layers in diabetic group compared with control group. This study concluded that diabetes caused major signs of pathology in the ultrastructure of photoreceptor layer of the rat retina.