Advances in Ubiquitination and Proteostasis in Retinal Degeneration.

Retinal degeneration (RD) is a group of chronic blinding diseases characterised by progressive retinal cell death. As the disease progresses, vision deteriorates due to retinal cell death and impaired retinal integrity, eventually leading to complete loss of vision. Therefore, the function and environmental homeostasis of the retina have an important impact on the pathogenesis and treatment of RD. Ubiquitination, as a complex post-translational modification process, plays an essential role in maintaining retinal homeostasis and normal function. It covalently combines ubiquitin with protein through a series of enzyme-mediated reactions, and participates in cell processes such as gene transcription, cell cycle process, DNA repair, apoptosis and immune response. At the same time, it plays a central role in protein degradation. There are two major protein degradation systems in eukaryotic cells: the ubiquitin-proteasome system and the autophagy-lysosomal system. The protein degradation pathway maintains retinal protein homeostasis by reducing abnormal protein accumulation in the retina through two modes of degradation. Either dysregulation of ubiquitination or disruption of protein homeostasis may lead to the development of RD. This article aims to comprehensively review recent research progress on ubiquitin-related genes, proteins and protein homeostasis in the pathogenesis of RD, and to summarize the potential targeted therapy strategies for it. The review is expected to provide valuable guidance for further development and application of ubiquitination in RD.