Department of Ophthalmology, Semmelweis University, Budapest, Hungary Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary.
Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary.
Invest Ophthalmol Vis Sci. 2014 May 20;55(6):3686-99. doi: 10.1167/iovs.13-13562.
Neurodegeneration as an early event of diabetic retinopathy preceding clinically detectable vascular alterations is a widely proven issue today. While there is evidence for the impairment of color vision and contrast sensitivity in early diabetes, suggesting deteriorated photoreceptor function, the underlying neuropathology of these functional alterations is still unknown. The aim of the present study was to investigate the effects of early diabetes on the outer retinal cells.
The retinal pigment epithelium, photopigment expression, and density and morphology of photoreceptors were studied using immunocytochemistry in streptozotocin-induced diabetes in two rat strains. The fine structure of photoreceptors and pigment epithelium was also investigated with transmission electron microscopy.
Here we found that retinal thickness was unchanged in diabetic animals and that no significant increase in the number of apoptotic cells was present. Although the density of cones expressing middle (M)- and shortwave (S)-sensitive opsins was similar in diabetic and control retinas, we detected remarkable morphologic signs of degeneration in the outer segments of diabetic rods, most M-cones, and some S-cones. A decrease in thickness and RPE65 protein immunoreactivity of the pigment epithelium were evident. Furthermore, an increased number of dual cones, coexpressing both M- and S-opsins, was detected at the peripheral retina of diabetic rats.
Degenerative changes of photoreceptors and pigment epithelium shown here prior to apoptotic loss of photoreceptors may contribute to functional alterations reported in diabetic human patients and different animal models, thus may serve as a potential model for testing the efficacy of neuroprotective agents in diabetes.
神经退行性变作为糖尿病视网膜病变的早期事件，先于临床可检测到的血管改变，这是当今已被广泛证实的问题。虽然有证据表明早期糖尿病会损害色觉和对比敏感度，表明光感受器功能恶化，但这些功能改变的潜在神经病理学仍然未知。本研究的目的是研究早期糖尿病对视网膜外细胞的影响。
使用免疫细胞化学方法研究链脲佐菌素诱导的两种大鼠糖尿病中的视网膜色素上皮细胞、视色素表达以及光感受器的密度和形态。还使用透射电子显微镜研究了光感受器和色素上皮的精细结构。
我们发现糖尿病动物的视网膜厚度没有变化，也没有明显增加凋亡细胞的数量。尽管表达中波（M）和短波（S）敏感视蛋白的锥体密度在糖尿病和对照组视网膜中相似，但我们在糖尿病棒状细胞的外节、大多数 M 锥体和一些 S 锥体中检测到明显的退行性病变迹象。色素上皮的厚度和 RPE65 蛋白免疫反应性明显下降。此外，在糖尿病大鼠的周边视网膜检测到更多的双锥体，这些双锥体同时表达 M-和 S-视蛋白。
与光感受器凋亡丢失之前显示的光感受器和色素上皮的退行性变化可能有助于解释糖尿病患者和不同动物模型中报告的功能改变，因此可能成为测试糖尿病神经保护剂疗效的潜在模型。
