Rod Photoreceptor-Specific Ablation of Metformin Target, AMPK, in a Preclinical Model of Autosomal Recessive Retinitis Pigmentosa.

ABSTRACT

Retinal gene therapies have shown tremendous progress in the past decade, but the sheer number of disease-causing mutations makes their applicability challenging. In this study we test our hypothesis that retinitis pigmentosa-associated retinal degeneration can be prevented through AMP-activated protein kinase (AMPK)-associated metabolic pathway reprogramming using a gene-independent model of degeneration and rescue. We show that recue of photoreceptor structure and function is not achieved through our model of metabolic reprogramming. These results suggest that RP may not be treatable through AMPK pathway modulation-based therapies.