Retinitis pigmentosa is a family of inherited retinal degenerations associated with gradual loss of photoreceptors, that ultimately leads to irreversible vision loss. The Royal College of Surgeon's (RCS) rat carries a recessive mutation affecting mer proto-oncogene tyrosine kinase (merTK), that models autosomal recessive disease. The aim of this study was to understand the glial, microglial, and photoreceptor changes that occur in different retinal locations with advancing disease. Pigmented RCS rats (RCS-p^+/LAV) and age-matched isogenic control rdy (RCS-rdy ⁺p⁺/LAV) rats aged postnatal day 18 to 6 months were evaluated for in vivo retinal structure and function using optical coherence tomography and electroretinography. Retinal tissues were assessed using high resolution immunohistochemistry to evaluate changes in photoreceptors, glia and microglia in the dorsal, and ventral retina. Photoreceptor dysfunction and death occurred from 1 month of age. There was a striking difference in loss of photoreceptors between the dorsal and ventral retina, with a greater number of photoreceptors surviving in the dorsal retina, despite being adjacent a layer of photoreceptor debris within the subretinal space. Loss of photoreceptors in the ventral retina was associated with fragmentation of the outer limiting membrane, extension of glial processes into the subretinal space that was accompanied by possible adhesion and migration of mononuclear phagocytes in the subretinal space. Overall, these findings highlight that breakdown of the outer limiting membrane could play an important role in exacerbating photoreceptor loss in the ventral retina. Our results also highlight the value of using the RCS rat to model sectorial retinitis pigmentosa, a disease known to predominantly effect the inferior retina.

色素性视网膜炎是与光感受器逐渐丧失相关的遗传性视网膜变性家族，最终导致不可逆的视力丧失。皇家外科医生学院（RCS）大鼠携带一种隐性突变，该突变会影响原常型隐性疾病的原癌基因酪氨酸激酶（merTK）。这项研究的目的是了解在疾病进展的不同视网膜位置发生的神经胶质，小神经胶质和感光细胞的变化。评估出生后18至6个月龄的色素RCS大鼠（RCS-p ^{+ /} LAV）和年龄匹配的等基因对照rdy（RCS-rdy ⁺ p ⁺ / LAV）大鼠体内使用光学相干断层扫描和视网膜电图检查视网膜结构和功能。使用高分辨率免疫组织化学评估视网膜组织，以评估视网膜和腹侧视网膜中感光细胞，神经胶质和小神经胶质的变化。从1个月大开始发生感光器功能障碍和死亡。背侧和腹侧视网膜之间光感受器的丢失有显着差异，尽管在视网膜下腔内邻近一层光感受器碎片，但在背视网膜中仍存在大量光感受器。腹侧视网膜中光感受器的丧失与外部限制膜的碎片，神经胶质突向视网膜下间隙的扩展，伴有可能的单核吞噬细胞在视网膜下间隙的粘附和迁移有关。总体，这些发现表明，外膜的破坏可能在加重腹膜视网膜感光细胞丧失中起重要作用。我们的研究结果还凸显了使用RCS大鼠建模扇形性色素性视网膜炎的价值，该疾病已知主要影响下视网膜。