Figure 3. Strategies for preserving vision.

(A) Gene augmentation delivers genetic materials encoding functional versions of mutant or lost proteins (loss-of-function mutations) through viral carriers. AAVs are the most commonly used carrier for gene augmentation. They deliver single-stranded DNA and are limited in packaging capacity to ~4.7 kb. LVs have greater capacity (~8kb) and carry single-stranded RNA genomes that, after reverse transcription, integrate into the host genome.

(B) Recent advances in gene editing (CRISPR/Cas nucleases, base editors, and prime editors) allow for increasingly precise and versatile corrections of mutations in the host genome, including in postmitotic photoreceptors. The illustrations in this panel are inspired by Raguram et al. (2022)¹⁴⁸ .

(C) Neuroprotective strategies use broadly trophic factors (e.g., CNTF) or leverage insights into the convergent pathogenesis to supply agents that bypass or boost affected pathways. A particular focus in neuroprotection is on preventing secondary cone degeneration in RP, including by delivery of the rod-derived cone viability factor (RdCVF) and its longer splice variant (RdCVFL).

(D) Homeostatic plasticity involving diverse mechanisms across retinal circuits can preserve visual function in the face of partial photoreceptor loss.