期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2017198118
关键词
retinal pigment epithelium; regeneration; inflammation; macrophage; microglia
资金
- NIH [T32EY17271, RO1-EY29410, P30-EY08098]
- University of Pittsburgh Medical Center (UPMC) Immune Transplant and Therapy Center
- Pennsylvania Lions Sight Conservation and Eye Research Foundation
- Whitman Center at the Marine Biological Laboratory
- Charles and Louella Snyder Retinal Regeneration Fund
- BrightFocus Foundation Macular Degeneration Research Program [M2016067]
- E. Ronald Salvitti Chair in Ophthalmology Research
- Martha Wandrisco Neff Research Award in Macular Degeneration
- University of Pittsburgh Honors College Health Sciences Fellowship
- Eye & Ear Foundation of Pittsburgh
- Research to Prevent Blindness
Research has revealed that zebrafish RPE has strong intrinsic regenerative potential, with elements of immune response identified as critical mediators in the regeneration process. Macrophage/microglia cells are responsive to RPE damage and essential for the timely progression of regenerative response.
Loss of the retinal pigment epithelium (RPE) because of dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms driving RPE regeneration. Here, utilizing transgenic and mutant zebrafish lines, pharmacological manipulations, transcriptomics, and imaging analyses, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. After genetic ablation, the RPE express immune-related genes, including leukocyte recruitment factors such as interleukin 34. We demonstrate that macrophage/microglia cells are responsive to RPE damage and that their function is required for the timely progression of the regenerative response. These data identify the molecular and cellular underpinnings of RPE regeneration and hold significant potential for translational approaches aimed toward promoting a pro -regenerative environment in mammalian RPE.
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