Mechanisms of photoreceptor protection upon targeting the <i>Nrl-Nr2e3</i> pathway.

ABSTRACT: Acute knockout of the rod photoreceptor transcription factor Nrl delays retinal degeneration in multiple mouse models of blindness, but the downstream transcriptomic changes that mediate these therapeutic effects are unknown. Here, we show that acute Nrl knockout causes upregulation of a subset of cone genes in rods as well as downregulation of rod genes, including the rod-specific transcriptional repressor Nr2e3. We hypothesized that Nr2e3 downregulation might mediate some of the therapeutic effects of Nrl knockout. Indeed, acute knockout of Nr2e3 prevents photoreceptor degeneration and preserves visual function in mice with mutations in the catalytic subunit of the rod-specific phosphodiesterase (Pde6b^rd10/rd10). Upregulation of

SUBMITTER: Murphy DP 

PROVIDER: S-EPMC12130857 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature