RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.

BACKGROUND

Age-related macular degeneration (AMD), a leading cause of vision loss in elderly individuals, is a multifactorial disease driven by genetic, environmental, and cellular aging processes. Emerging evidence highlights the critical role of ribonucleic acid (RNA) splicing dysfunction in AMD pathogenesis, with a focus on the U1 small nuclear ribonucleoprotein (U1 snRNP) complex, a key spliceosome component. U1 snRNPs ensure the fidelity of RNA cotranscription and pre-mRNA splicing initiation, and their dysfunction has been implicated in neurodegenerative disorders and other age-related diseases.

MAIN BODY: This narrative review explores the impact of U1 snRNP dysregulation on retinal cells, focusing on its role in transcriptomic instability, impaired protein homeostasis, cellular stress, impaired autophagy, and inflammation, which are important features of AMD pathogenesis. Finally, we propose that targeting U1 snRNP dysfunction could provide a novel therapeutic approach to slow, prevent, or restore retinal degeneration, offering insights into broader implications for age-related diseases.

SHORT

CONCLUSION

Understanding the molecular mechanisms underlying U1 snRNP dynamics in retinal health and degeneration is essential for developing innovative and effective treatments for AMD, which may provide ways to delay or reverse the effects of aging and associated diseases.