Probing Proteostatic Stress in Degenerating Photoreceptors Using Two ComplementaryIn VivoReporters of Proteasomal Activity

Inherited retinal degenerations originate from mutations in >300 genes, many of which cause the production of misfolded mutant photoreceptor proteins that are ultimately degraded by the ubiquitin-proteasome system (UPS). It was previously shown that rod photoreceptors in multiple mouse models of retinal degeneration suffer from proteostatic stress consisting of an insufficient cellular capacity for degrading UPS substrates. In this study, we...