Exploring Molecular Pathways in Refractive Errors Associated with Inherited Retinal Dystrophies

Abstract

The term inherited retinal dystrophies (IRDs) refers to a diverse range of conditions characterized by retinal dysfunction, and mostly deterioration, leading to a gradual decay of the visual function and eventually to total vision loss. IRDs have a global impact on about 1 in every 3000 to 4000 individuals. However, the prevalence statistics might differ significantly depending on the exact type of dystrophy and the demographic being examined. The cellular pathophysiology and genetic foundation of IRDs have been extensively studied, however, knowledge regarding associated refractive errors remain limited. This review aims to clarify the cellular and molecular processes that underlie refractive errors in IRDs. We did a thorough search of the current literature (Pubmed, accession Feb 2024), selecting works describing phenotypic differences among genes-related to IRDs, particularly in relation to refractive errors. First, we summarize the wide range of IRDs and their genetic causes, describing the genes and biological pathways connected to the etiology of the disease. We then explore the complex relationship between refractive errors and retinal dysfunction, including how the impairment of the vision-related mechanisms in the retina can affect ocular biometry and optical characteristics. New data about the involvement of aberrant signaling pathways, photoreceptor degeneration, and dysfunctional retinal pigment epithelium (RPE) in the development of refractive errors in IRDs have been examined. We also discuss the therapeutic implications of refractive defects in individuals with IRD, including possible approaches to treating visual impairments. In addition, we address the value of using cutting-edge imaging methods and animal models to examine refractive errors linked to IRDs and suggest future lines of inquiry for identifying new targets for treatment. In summary, this study presents an integrated understanding of the cellular and molecular mechanisms underlying refractive errors in IRDs. It illuminates the intricacies of ocular phenotypes in these conditions and offers a tool for understanding mechanisms underlying isolated refractive errors, besides the IRD-related forms.

Keywords

• myopia
• hyperopia
• eye development
• genotype-phenotype correlation
• neurotransmitter signaling
• axial length modulation