Abstract
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder characterized by retinal degeneration leading to blindness. This study investigates the therapeutic efficacy of N-Acetylcysteine (NAC), an oxygen free radical scavenger, in ameliorating retinal degeneration associated with BBS using a murine model of BBS10. BBS is caused by mutations in BBS genes, the protein products of which are involved in ciliary function; mutant or absent BBS10 protein disrupts the assembly of the BBSome protein complex, disturbing ciliary trafficking and leading to photoreceptor cell dysfunction and death. Photoreceptor function can be assessed using the electroretinogram (ERG), and anatomy can be assessed using optical coherence tomography (OCT) and histology to demonstrate progressive degeneration over time. This study utilizes Bbs10 -/- mice to assess the effect of NAC supplementation on retinal degeneration. Results reveal that NAC supplementation ameliorates the progressive degeneration of the retinal outer nuclear layer (ONL) on OCT and mitigates the loss-of-b-wave ERG phenotype observed in Bbs10 -/- mice. The ERG b-wave is generated by retinal bipolar cells after synapsing with photoreceptors which have been hyperpolarized by light exposure. Reducing the loss-of-b-wave phenotype may indicate improved synaptic function. Synaptic staining demonstrates a correlation between the absence of an electropositive b-wave and mislocalized presynaptic terminals, highlighting the significance of synaptic integrity for retinal function. These findings suggest NAC as a promising therapeutic intervention for managing BBS10-related retinal degeneration.