Leach Lyndsay L, Gonzalez Rebecca G, Jayawardena Sayuri U, Gross Jeffrey M
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Cell Rep. 2025 Sep 19;44(10):116325. doi: 10.1016/j.celrep.2025.116325.
The retinal pigment epithelium (RPE) surrounds the posterior eye and maintains the health and function of the photoreceptors. Consequently, RPE dysfunction or damage has a devastating impact on vision. Due to complex etiologies, there are currently no cures for patients with RPE degenerative diseases, which remain some of the most prevalent causes of vision loss worldwide. Further, owing to a limited capacity for mammalian tissue repair, we know little about how the RPE regenerates. Here, we utilize zebrafish to uncover mechanisms driving intrinsic RPE regeneration. We show that microglia are indispensable for repair and present evidence that supports the role of interleukin-34 in recruiting macrophages/microglia to the RPE injury site. Further, we identify aberrant RPE injury site debris accumulation due to decreased macrophage/microglia localization, and we find that phagocytosis is an important mechanism driving debris clearance. Together, our results identify new regenerative functions of macrophages/microglia after RPE damage.
视网膜色素上皮（RPE）环绕眼球后部，维持光感受器的健康和功能。因此，RPE功能障碍或损伤会对视力产生毁灭性影响。由于病因复杂，目前尚无针对RPE退行性疾病患者的治愈方法，这些疾病仍是全球范围内视力丧失的一些最常见原因。此外，由于哺乳动物组织修复能力有限，我们对RPE如何再生知之甚少。在此，我们利用斑马鱼来揭示驱动RPE内在再生的机制。我们表明，小胶质细胞对修复不可或缺，并提供证据支持白细胞介素-34在将巨噬细胞/小胶质细胞募集到RPE损伤部位中的作用。此外，我们发现由于巨噬细胞/小胶质细胞定位减少，RPE损伤部位出现异常碎片堆积，并且我们发现吞噬作用是驱动碎片清除的重要机制。总之，我们的结果确定了RPE损伤后巨噬细胞/小胶质细胞的新再生功能。
