Comparative single-cell analysis of multiple models of retinitis pigmentosa reveals common pro-survival mechanisms activated in photoreceptors

The vast genetic heterogeneity of RP results in highly variable disease phenotypes, yet the identification of shared, mutation-independent mechanisms could provide a foundation for broadly applicable therapeutic strategies. To explore such mechanisms, we generated scRNA-seq datasets across three key timepoints in two RP mouse models, rd10 and P347S, and integrated them with public datasets from rd1 and AdipoR1-KO models.

Time-course differential expression and gene regulatory network analyses revealed a conserved transcriptional response to retinal degeneration across photoreceptor types and disease models. Transcription factors such as Cebpd, Stat3, and E2f6 emerged as central regulators, consistently upregulated and potentially mediating pro-survival mechanisms. IEGs like Junb, Fosb, and Egr1 were consistently activated, configuring an early response to stress associated to apoptotic responses.