Fernández-Sánchez Laura, Esquiva Gema, Pinilla Isabel, Lax Pedro, Cuenca Nicolás
Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Front Neuroanat. 2018 Jun 29;12:55. doi: 10.3389/fnana.2018.00055. eCollection 2018.
Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases involving a progressive degeneration of photoreceptor cells. Following the loss of photoreceptors, retinal vascularization tends to decrease, which seems to play a role in the degenerative process of retinal cells. This study reports changes in retinal vascular network architecture in the P23H rat model of RP at different stages of retinal degeneration. Homozygous P23H line-3 rats of ages ranging from 18 days to 16 months were used in this study. Age-matched Sprague-Dawley (SD) rats were used as control animals. Vertical sections and wholemount retinas were immunolabeled for type IV collagen or stained using NADPH diaphorase histochemistry, and retinal vascular networks were drawn using a camera lucida. The superficial and deep capillary plexus (DCP) were fully developed at P18 in P23H rat retinas and showed no differences from the control animals. In 4-month-old P23H rat retinas, the superficial and intermediate capillary plexus were similar to those observed in age-matched SD rats, but a reduction in the DCP could be observed in these animals, with a significant decrease in both capillary density and capillary loops. At 16 months, the DCP was completely lost, and only vessels exhibiting an abnormal, tortuous dead-end could be observed. The middle capillary plexus had virtually disappeared at this age. Only perpendicular vessels connecting the superficial and DCP were found. The superficial plexus showed no changes in the vascular surface with age. In RP, photoreceptor loss is accompanied by degenerative changes in the retinal vascular network. The disruption of the capillary plexus, with loss of capillary density and capillary loops, can hamper the normal supply of oxygen and nutrients to retinal cells, thus accelerating retinal degeneration. Therefore, changes in retinal vascularization must be taken into account in the design of therapies targeting retinal degenerative diseases.
视网膜色素变性（RP）是一组遗传性视网膜退行性疾病，涉及光感受器细胞的进行性退化。在光感受器丧失后，视网膜血管化倾向于减少，这似乎在视网膜细胞的退化过程中起作用。本研究报告了RP的P23H大鼠模型在视网膜退化不同阶段视网膜血管网络结构的变化。本研究使用了年龄在18天至16个月之间的纯合P23H 3系大鼠。年龄匹配的Sprague-Dawley（SD）大鼠用作对照动物。垂直切片和视网膜全层标本用IV型胶原进行免疫标记或用NADPH黄递酶组织化学染色，并用明视野显微镜绘制视网膜血管网络。P23H大鼠视网膜在P18时浅表和深层毛细血管丛（DCP）已完全发育，与对照动物无差异。在4个月大的P23H大鼠视网膜中，浅表和中间毛细血管丛与年龄匹配的SD大鼠相似，但在这些动物中可观察到DCP减少，毛细血管密度和毛细血管环均显著降低。在16个月时，DCP完全消失，仅观察到呈现异常、扭曲盲端的血管。此时中间毛细血管丛几乎消失。仅发现连接浅表和DCP的垂直血管。浅表丛的血管表面随年龄无变化。在RP中，光感受器丧失伴随着视网膜血管网络的退行性变化。毛细血管丛的破坏，伴随着毛细血管密度和毛细血管环的丧失，会妨碍视网膜细胞正常的氧气和营养供应，从而加速视网膜退化。因此，在设计针对视网膜退行性疾病的治疗方法时，必须考虑视网膜血管化的变化。
