Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing

Retinitis pigmentosa (RP) is the most common cause of inherited blindness, with mutations in splicing factors playing a significant role in its pathogenesis. Many scientists have been puzzled by the fact that mutations in several key spliceosomal components have such a confined effect on the retina. In this review, we summarize findings gained from studies using cell culture, animal models, and retinal organoids to better understand the molecular mechanisms underlying the tissue specificity of splicing factor dysfunction to retinal degeneration. Although RP currently has no definitive cure, recent advances in gene therapy, antisense oligonucleotides, and cell transplantation are opening new therapeutic approaches to slow disease progression and preserve retinal function. We also discuss the strengths and challenges of current strategies and point to the critical improvements required for their successful clinical application.