Département de Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Invest Ophthalmol Vis Sci. 2011 Nov 21;52(12):8993-9004. doi: 10.1167/iovs.11-8423.
Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model.
Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either vegetation-based diets (n = 13) or standard rat chow (n = 26). Although plant-fed animals exhibited uniform body weight and blood glucose levels over time, nearly 60% of rat chow-raised animals developed diabetes-like symptoms (test group). Animals were killed, and their eyes and vitreous were processed for immunochemistry.
Compared with plant-fed animals, diabetic animals showed many abnormal vascular features, including vasodilation, tortuosity, and pericyte loss within the blood vessels, hyperproteinemia and elevated ratios of proangiogenic and antiangiogenic growth factors in the vitreous, and blood-retinal barrier breakdown. Furthermore, there were statistically significant decreases in retinal cell layer thicknesses and densities, accompanied by profound alterations in glia (downregulation of glutamine synthetase, glutamate-aspartate transporter, upregulation of glial fibrillar acidic protein) and many neurons (reduced expression of protein kinase Cα and Cξ in bipolar cells, axonal degeneration in ganglion cells). Cone photoreceptors were particularly affected, with reduced expression of short- and mid-/long-wavelength opsins. Hypercaloric diet nondiabetic animals showed intermediate values.
Simple dietary modulation of P. obesus induces a rapid and severe phenotype closely resembling human type 2 DR. This species presents a valuable novel experimental model for probing the neural (especially cone photoreceptor) pathogenic modifications that are difficult to study in humans and for screening therapeutic strategies.
糖尿病视网膜病变（DR）是失明的主要原因，但相关的动物模型并不常见。沙鼠（Psammomys obesus）表现出饮食诱导的代谢综合征，可能构成相关模型。
将成年沙鼠（n = 39）在圈养中饲养 4 至 7 个月，并分别喂食植物性饮食（n = 13）或标准大鼠饲料（n = 26）。尽管植物性饮食喂养的动物在一段时间内体重和血糖水平保持一致，但近 60%的大鼠饲料喂养动物出现类似糖尿病的症状（实验组）。处死动物，对其眼睛和玻璃体进行免疫化学处理。
与植物性饮食喂养的动物相比，糖尿病动物表现出许多异常的血管特征，包括血管扩张、扭曲和血管周细胞丢失、玻璃体内高蛋白血症和促血管生成与抗血管生成生长因子比例升高，以及血视网膜屏障破坏。此外，视网膜细胞层厚度和密度显著降低，胶质（谷氨酸合成酶、谷氨酸-天冬氨酸转运体下调，胶质纤维酸性蛋白上调）和许多神经元（双极细胞中蛋白激酶 Cα 和 Cξ表达减少，节细胞轴突变性）发生深刻改变。视锥细胞尤其受到影响，短波长/中长波长视蛋白表达减少。高热量饮食非糖尿病动物表现出中间值。
简单的饮食调节可诱导沙鼠迅速产生严重的表型，与人类 2 型 DR 非常相似。该物种为研究人类中难以研究的神经（特别是视锥细胞）致病改变以及筛选治疗策略提供了有价值的新型实验模型。
