Kozhevnikova O S, Fursova A Zh, Markovets A M, Telegina D V, Muraleva N A, Kolosova N G
The Federal Research Center Institute of Cytology and Genetics, 10, pr. acad. Lavrentjev pr., Novosibirsk, 630090, Russian Federation; email:
Adv Gerontol. 2018;31(3):339-344.
Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. By clinical signs, there are two forms of AMD: the atrophic or dry (~ 90% of all cases) and wet or neovascular AMD (~10% of cases). Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet AMD. However, there are emerging signals that anti-VEGF treatment can potentially increase development of atrophic AMD. There is neither a treatment of the dry AMD due poor understanding of the pathogenesis and retina aging process in general. We have shown previously that senescence-accelerated OXYS rats are a suitable model of dry AMD. Signs of retinopathy in OXYS rats manifest themselves by age 3 months against the background of a decline in the number of retinal pigment epithelium (RPE) cells and an alteration of choroidal microcirculation. Herein, we compared retinal expression of proteins VEGF and PEDF (pigment epithelium-derived factor) between OXYS and Wistar rats (control). The amount of the VEGF protein increased with age in the retina of both rat strains from 3 months of age. From age 3 to 24 months, this parameter was significantly lower in OXYS rats than in Wistar rats. PEDF protein concentration was significant lower in the OXYS retina only at the age of 3 months. We can conclude that development of retinopathy in OXYS rats takes place at reduced concentrations of VEGF and PEDF. Because RPE cells control the VEGF-PEDF balance, an RPE-targeted approach is a logical choice for AMD treatment and for decreasing adverse effects of anti-VEGF treatment.
年龄相关性黄斑变性（AMD）是老年人视力丧失的主要原因。根据临床症状，AMD有两种形式：萎缩性或干性AMD（约占所有病例的90%）和湿性或新生血管性AMD（约占病例的10%）。抗血管内皮生长因子（VEGF）玻璃体内注射剂是湿性AMD唯一成功的治疗方法。然而，有新的迹象表明，抗VEGF治疗可能会增加萎缩性AMD的发生。由于对干性AMD的发病机制和视网膜衰老过程总体了解不足，目前尚无针对干性AMD的治疗方法。我们之前已经表明，衰老加速的OXYS大鼠是干性AMD的合适模型。OXYS大鼠的视网膜病变迹象在3个月大时就会出现，同时伴有视网膜色素上皮（RPE）细胞数量减少和脉络膜微循环改变。在此，我们比较了OXYS大鼠和Wistar大鼠（对照）视网膜中VEGF和PEDF（色素上皮衍生因子）蛋白的表达。两种品系大鼠视网膜中VEGF蛋白的含量从3个月大开始随年龄增加。从3个月到24个月，OXYS大鼠的这一参数显著低于Wistar大鼠。仅在3个月大时，OXYS大鼠视网膜中的PEDF蛋白浓度显著降低。我们可以得出结论，OXYS大鼠视网膜病变的发生是在VEGF和PEDF浓度降低的情况下发生的。由于RPE细胞控制着VEGF - PEDF平衡，针对RPE的治疗方法是AMD治疗以及减少抗VEGF治疗不良反应的合理选择。
