Primary cilia are conserved organelles that integrate extracellular cues into intracellular signals and are critical for diverse processes, including cellular development and repair responses. Deficits in ciliary function cause multisystemic human diseases known as ciliopathies. In the eye, atrophy of the retinal pigment epithelium (RPE) is a common feature of many ciliopathies. However, the roles of RPE cilia in vivo remain poorly understood. In this study, we first found that mouse RPE cells only transiently form primary cilia. We then examined the RPE in the mouse model of Bardet-Biedl Syndrome 4 (BBS4), a ciliopathy associated with retinal degeneration in humans, and found that ciliation in BBS4 mutant RPE cells is disrupted early during development. Next, using a laser-induced injury model in vivo, we found that primary cilia in RPE reassemble in response to laser injury during RPE wound healing and then rapidly disassemble after the repair is completed. Finally, we demonstrated that RPE-specific depletion of primary cilia in a conditional mouse model of cilia loss promoted wound healing and enhanced cell proliferation. In summary, our data suggest that RPE cilia contribute to both retinal development and repair and provide insights into potential therapeutic targets for more common RPE degenerative diseases.

初级纤毛是保守的细胞器，可将细胞外信号整合到细胞内信号中，对于细胞发育和修复反应等多种过程至关重要。纤毛功能缺陷会导致称为纤毛病的多系统人类疾病。在眼睛中，视网膜色素上皮（RPE）萎缩是许多纤毛病的共同特征。然而，RPE 纤毛在体内的作用仍知之甚少。在这项研究中，我们首先发现小鼠 RPE 细胞仅短暂地形成初级纤毛。然后，我们检查了 Bardet-Biedl 综合征 4 (BBS4)（一种与人类视网膜变性相关的纤毛病）小鼠模型中的 RPE，发现 BBS4 突变 RPE 细胞的纤毛在发育早期就被破坏。接下来，利用体内激光诱导损伤模型，我们发现RPE中的初级纤毛在RPE伤口愈合过程中响应激光损伤而重新组装，然后在修复完成后迅速分解。最后，我们证明，在条件性纤毛缺失小鼠模型中，RPE 特异性去除初级纤毛可促进伤口愈合并增强细胞增殖。总之，我们的数据表明 RPE 纤毛有助于视网膜发育和修复，并为更常见的 RPE 退行性疾病的潜在治疗靶点提供见解。