Pde6a encodes a cGMP-specific phosphodiesterase. Mutations in PDE6A are pivotal in autosomal recessive retinitis pigmentosa (RP43), and this gene is thus of great importance in understanding inherited retinal diseases [1,2,4-8].

In Pde6a-related retinal degeneration, recent research has shown promise in treatment approaches. Engineered base editing (BE) and prime editing (PE) systems, especially PE, can efficiently rescue a target point mutation in an RP mouse model carrying the Pde6a (c.2009A > G, p.D670G) mutation with minimal bystander effects. The optimal PE system, delivered via dual adeno-associated virus (AAV), precisely corrects the pathogenic mutation, restores PDE6A protein expression, preserves photoreceptors, and rescues retinal function in Pde6a mice [1]. Additionally, all-in-one AAV-SaCas9-mediated Nrl gene inactivation can prevent retinal degeneration in a Pde6a mouse model with Pde6anmf363/nmf363 mutation, improving photoreceptor cell survival and rescuing retinal function [3]. Gene augmentation studies in Asp670Gly mouse and dog models using adeno-associated virus vectors have also restored some rod-mediated function and preserved retinal structure [2].

In conclusion, Pde6a is crucial in maintaining normal retinal function, and its dysfunction leads to retinal degeneration, specifically autosomal recessive retinitis pigmentosa. Studies on Pde6a-related mouse models have provided valuable insights into potential gene-therapy-based treatment strategies for this form of retinal disease [1,2,3].