Single-cell–resolution map of human retinal pigment epithelium helps discover subpopulations with differential disease sensitivity

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Abstract
Significance: Retinal degenerative diseases affect specific regions of the retinal pigment epithelium (RPE), suggesting the presence of functionally different RPE subpopulations. To identify these subpopulations in human eyes, we generated the first complete morphometric map of the RPE at single-cell resolution using artificial intelligence–based software. We identified five concentric RPE subpopulations, including a ring of RPE cells with cell area similar to macula in the periphery of the eye. Moreover, we found that specific RPE subpopulations are differentially susceptible to monogenic and polygenic retinal diseases. The results obtained here will allow study of molecular and functional RPE differences responsible for regional retinal diseases and will help develop precise cell and gene therapies for specific degenerative eye diseases.

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