Park S-H, Park J-W, Park S-J, Kim K-Y, Chung J-W, Chun M-H, Oh S-J
Department of Anatomy, College of Medicine, The Catholic University of Korea, Socho-gu, Seoul, Korea.
Diabetologia. 2003 Sep;46(9):1260-8. doi: 10.1007/s00125-003-1177-6. Epub 2003 Jul 31.
AIMS/HYPOTHESIS: Neurodegenerative changes in the diabetic retina occurring before diabetic retinopathy could be inevitable by the altered energy (glucose) metabolism, in the sense that dynamic image-processing activity of the retinal neurons is exclusively dependent on glucose. We therefore investigated the morphological changes in the neural retina, including neuronal cell death, of a streptozotocin-induced model of diabetes.
Streptozotocin was intravenously injected. Rats were maintained hyperglycaemic without insulin treatment for 1 week and 4, 8, 12, and 24 weeks, respectively. Diabetic retinas were processed for histology, electron microscopy, and immunohistochemistry using the TUNEL method.
A slight reduction in the thickness of the inner retina was observed throughout the diabetic retinas and a remarkable reduction was seen in the outer nuclear layer 24 weeks after the onset of diabetes. The post-synaptic processes of horizontal cells in the deep invaginations of the photoreceptors showed degeneration changes from 1 week onwards. A few necrotic ganglion cells were observed after 4 weeks. At 12 weeks, some amacrine cells and a few horizontal cells showed necrotic features. Three to seven cellular layers in the outer nuclear layer and nerve terminals, rolled by the fine processes of the Müller cells near the somata of the degenerated ganglion cells, were apparent at 24 weeks. Apoptosis appeared in a few photoreceptor cells at 4 weeks, and the number of apoptotic photoreceptors increased thereafter.
CONCLUSION/INTERPRETATION: These findings suggest that the visual loss associated with diabetic retinopathy could be attributed to an early phase of substantial photoreceptor loss, in addition to later microangiopathy.
目的/假设：鉴于视网膜神经元的动态图像处理活动完全依赖葡萄糖，糖尿病视网膜病变发生之前，糖尿病视网膜中的神经退行性变化可能因能量（葡萄糖）代谢改变而不可避免。因此，我们研究了链脲佐菌素诱导的糖尿病模型神经视网膜的形态学变化，包括神经元细胞死亡。
静脉注射链脲佐菌素。大鼠在不进行胰岛素治疗的情况下分别维持高血糖1周、4周、8周、12周和24周。使用TUNEL法对糖尿病视网膜进行组织学、电子显微镜和免疫组织化学处理。
在整个糖尿病视网膜中观察到内视网膜厚度略有减少，糖尿病发病24周后外核层明显变薄。从第1周起，光感受器深凹处水平细胞的突触后过程出现退化变化。4周后观察到一些坏死的神经节细胞。在12周时，一些无长突细胞和少数水平细胞呈现坏死特征。在24周时，在外核层和神经末梢可见三到七个细胞层，由退化神经节细胞胞体附近的米勒细胞的精细突起包裹。4周时少数光感受器细胞出现凋亡，此后凋亡光感受器数量增加。
结论/解读：这些发现表明，除了后期的微血管病变外，与糖尿病视网膜病变相关的视力丧失可能归因于早期大量光感受器丧失。
