Abstract

Dysfunction and degeneration of retinal pigment epithelium (RPE) cells are common pathological features observed in various retinal degenerative diseases. It has been proposed to treat these diseases by either protecting RPE cells or replacing them with new RPE cells derived from stem cells. However, the development of effective therapeutic strategies is still limited due to the insufficient understanding of the pathogenic factors involved in retinal degeneration and their impact on the function and survival of RPE cells. In this study, we employed genome-scale CRISPR knockout (KO) screening in human RPE cells to identify genes critical for RPE cell survival. Over 300 genes were identified, including well-established housekeeping genes as well as several candidate genes previously linked to retinal degeneration, many of which still lack comprehensive investigation. Among these, we further validated PRPF38B, which was both enriched in our screening and highlighted in a prior family-based linkage study, as essential for RPE cell survival, thus confirming the effectiveness of our approach. As a component of the spliceosome, we found that PRPF38B is crucial for functions specific to RPE cells, offering new insights into its role in retinal degeneration. Our study presents a novel approach for investigating risk genes associated with retinal diseases and may inspire future research on RPE cells and vision disorders.