Targeting Mitophagy in Retinal Degenerations

01/01/2026 to 31/12/2026

Retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are among the leading causes of blindness worldwide. Both disorders are characterized by mitochondrial dysfunction, oxidative stress, and impaired proteostasis. Our previous research has demonstrated that inhibition of Valosin-Containing Protein (VCP) helps stabilize proteostasis, improves mitochondrial quality control, and protects photoreceptors in RP models. This project explores whether combining VCP inhibition (ML240) with mitophagy activation through Urolithin A can exert synergistic neuroprotective effects. The study emphasizes the BNIP3/NIX-mediated mitophagy pathway, a key but poorly understood mechanism of mitochondrial homeostasis in the retina. Using ex vivo retinal cultures from rd10 mice (RP model) and an iPSC-RPE/porcine retina co-culture system (AMD model), we will assess the effects of this combined treatment impacts mitophagy, oxidative stress, cell survival, and retinal integrity. This collaborative project between the Boya Lab (University of Fribourg) and the Ueffing Lab (University of Tübingen) aims to develop a new, mutation-independent therapy to preserve retinal structure and function, paving the way for translational approaches in human retinal diseases.