Aged‐related changes in connexins‐based mediated intercellular channels in retina

• DOI: 10.1111/aos.17398
• Publication Date: 2025-01-20T00:37:32Z
• Authors: Alicia Domenech‐B...; Alejandro Ponce‐Mora; Antonella Locascio; Nicolle Salazar; Lucía Gimeno Mall...; Eloy Bejarano

Aims/Purpose: Connexins (Cxs) are a family of structurally‐related transmembrane proteins that form gap junction channels. These channels are essential for direct intercellular communication in many tissues. Cxs play a crucial role in retina homeostasis and visual information processing. Cxs connect photoreceptors, horizontal cells, bipolar cells, amacrine cells and ganglion cells in the mammalian retina. They are proposed as therapeutic targets for several retinal diseases. Although retinal aging is considered a risk factor for different retinal disorders, it remains unclear if the retinal connectome changes with age. This study systematically analyzes the relationship between retinal Cxs isoforms and age.Methods: Retinas from C57BL/6J mice were harvested at 1‐, 4‐, 12‐ and 24 months. Immunohistochemical and qPCR analysis for various retinal Cxs isoforms were performed, including Cx50, Cx43, Cx36 and Cx57. Colocalization analysis was carried out using antibodies against different retinal layers or retinal cell types. Images were captured using the EVOS M7000 microscope, and 3D modelling was performed using the Celleste 3D Deconvolution Module.Results: Differences in expression and location were found in different aged‐groups in an isoform‐dependent manner. For example, Cx50 is expressed in ganglion cell layer in young retina and, as mice aged, Cx50 is highly expressed in Müller cells. Cx36 is highly expressed in both OPL and IPL; higher levels and accumulation of Cx36 are found in aged retina.Conclusions: This study provides new pieces of evidence about the impact of aging in the retinal connexins‐based connectome. A comprehensive understanding of the impact of aging on the retinal connectome is imperative for the design of connexins‐mimetic peptides as therapeutic tools in the treatment of connexin‐related retinal diseases.Funding: RYC 2018‐024434‐I, MINECO PID 2020‐119466RB‐I00, and FUSP‐PPC‐19‐B53C4C64.