Gene editing of JNK alleviates sodium iodate-induced retinal degeneration in mice

Dry age-related macular degeneration (dry AMD) still lacks effective treatment strategies due to its complex mechanisms. Although c-Jun N-terminal kinase (JNK) signaling has been reported to be associated with retinal degeneration in dry AMD, the efficacy of JNK gene editing in treating dry AMD remains unclear. This study aims to investigate the protective potential of JNK genetic inhibition in a sodium iodate (SI)-induced retinal degeneration model that recapitulates the key features of human dry AMD.

A retinal degeneration model was constructed from a single intraperitoneal injection of 50 mg/kg body weight SI into C57BL/6 J mice. The retina was examined by electroretinography (ERG), fundus imaging, optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and whole-mount ZO-1 immunofluorescence staining. Protein levels were determined using Western blotting. Jnk1^+/-Jnk2^-/- mice were obtained by crossbreeding Jnk2^-/- mice with Jnk1^+/- mice.

In C57BL/6 J mice, SI robustly activated JNK signaling in the retinal pigment epithelium (RPE)/choroid, triggering a parallel loss of retinal function and structural integrity. By contrast, Jnk1^+/-Jnk2^-/- mice were largely protected: both the SI-evoked JNK response in the RPE/choroid and the ensuing retinal degeneration were markedly attenuated.

Gene editing of JNK is effective in ameliorating SI-driven retinal injury and may serve as a promising therapeutic avenue for dry AMD.