Department of Biomedical Engineering, University of Houston, Houston, Texas, USA.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
FASEB J. 2022 May;36(5):e22284. doi: 10.1096/fj.202101562RR.
Prph2 is a photoreceptor-specific tetraspanin with an essential role in the structure and function of photoreceptor outer segments. PRPH2 mutations cause a multitude of retinal diseases characterized by the degeneration of photoreceptors as well as defects in neighboring tissues such as the RPE. While extensive research has analyzed photoreceptors, less attention has been paid to these secondary defects. Here, we use different Prph2 disease models to evaluate the damage of the RPE arising from photoreceptor defects. In Prph2 disease models, the RPE exhibits structural abnormalities and cell loss. Furthermore, RPE functional defects are observed, including impaired clearance of phagocytosed outer segment material and increased microglia activation. The severity of RPE damage is different between models, suggesting that the different abnormal outer segment structures caused by Prph2 disease mutations lead to varying degrees of RPE stress and thus influence the clinical phenotype observed in patients.
Prph2 是一种感光细胞特异性四跨膜蛋白，在感光细胞外节的结构和功能中起关键作用。PRPH2 突变导致多种视网膜疾病，其特征是感光细胞退化以及邻近组织（如 RPE）缺陷。虽然已经有大量研究分析了感光细胞，但对这些继发性缺陷的关注较少。在这里，我们使用不同的 Prph2 疾病模型来评估由感光细胞缺陷引起的 RPE 损伤。在 Prph2 疾病模型中，RPE 表现出结构异常和细胞损失。此外，还观察到 RPE 功能缺陷，包括吞噬的外节物质清除能力受损和小胶质细胞激活增加。不同模型中 RPE 损伤的严重程度不同，表明 Prph2 疾病突变引起的不同异常外节结构导致不同程度的 RPE 应激，从而影响患者中观察到的临床表型。
