Mutations destabilizing rod opsin are one of the main factors that lead to retinal degeneration. Focusing on the analysis on the P23H rod opsin mutation, that is the most common mutation among autosomal dominant retinis pigmentosa patients in North America, Palczewski and co-workers reported compound YC-001 as the first non-retinal modulator of rod opsin with both inverse and non-competitive antagonist activities [2]. YC-001 was discovered by a cellular high-throughput screening; it showed an interesting activity in various in vitro binding assays, and showed in vivo efficacy in a mouse model of bright light-induced retinal degeneration, thus supporting the possible therapeutic application of this compound. The authors were not able to obtain a crystal structure of the YC-001:opsin complex; however, this study paves the way for the design and development of new candidate drugs for the treatment of pathologies associated with retinal degeneration.
