INVESTIGATING THE MORPHOLOGY AND ULTRA-STRUCTURE OF IMPG2-RELATED RETINAL DEGENER-ATION USING ZEBRAFISH KNOCK-OUT MODEL

Retinitis pigmentosa (RP) is one of the most prevalent inherited retinal dystrophies, characterized by the progressive degeneration of photoreceptors. Recent studies have identified nonsense mutations in the interphotoreceptor matrix proteoglycan 2 (IMPG2) gene as causative of autosomal recessive forms of RP in humans. IMPG2 encodes a proteoglycan localized in the interphotoreceptor matrix (IPM), which surrounds the outer segments and ellipsoids of retinal photoreceptors and likely contributes to IPM integrity through interactions with other extracellular matrix components. We employed zebrafish as a model organism to investigate how IMPG2 loss compromises extracellular matrix stability and leads to photoreceptor degeneration and functional retinal decline. Due to its retinal architecture, which closely resembles the human mac-ula, zebrafish offer a powerful system for studying retinal diseases. We characterized the zebrafish IMPG2 paralogues, impg2a and impg2b, and examined the morphological and ultrastructural con-sequences of gene loss in 7-day-post-fertilization (dpf) knock-out mutants. Our analyses revealed marked alterations in ocular mor-phology associated with the absence of these genes, highlighting their essential role in eye development and suggesting that matrix disorganization may drive disease onset. Ultimately, this study aims to validate the impg2-deficient zebrafish line as a model for screening therapeutic agents capable of preserving interphotore-ceptor matrix integrity, with promising implications for treating a wide range of retinal degenerative diseases.