Exploring IMPG2: A New Therapeutic Target for Retinitis Pigmentosa Treatment

Retinitis pigmentosa (RP) is an inherited retinal dystrophy that leads to progressive vision loss as a result of the degeneration of photoreceptor cells. This disorder is characterized by a gradual decline in visual function [1]. Despite advancements in understanding its genetic basis, effective treatments for RP remain elusive. Recent research has identified nonsense mutations in the IMPG2 gene as a cause of autosomal recessive RP in humans. IMPG2 encodes a critical proteoglycan that plays a vital role in maintaining the interphotoreceptor matrix (IPM), an extracellular structure that helps stabilize photoreceptor outer segments, ensuring proper retinal function and health [2]. However, the precise molecular mechanisms by which the loss of IMPG2 leads to retinal degeneration are not fully understood. To explore these mechanisms, we utilized zebrafish (Danio rerio) as a model organism due to their highly conserved retinal structure and their suitability for genetic studies. After characterizing the zebrafish paralogs impg2a and impg2b [2], we generated impg2-deficient embryos using morpholino oligonucleotides (MO) and knock-out (KO) mutants. Our results revealed significant retinal defects upon impg2 depletion, including alterations in the extracellular matrix architecture and damage to both photoreceptors and other retinal layers. These findings demonstrate that IMPG2 plays a crucial role in maintaining the structure of the entire retina and, therefore, we propose it as a potential therapeutic target for RP and related retinal disorders, offering promising avenues for future therapeutic development.