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Enhancing Retinal Photoreceptor Neurite Outgrowth with Small Molecules and Growth Factors

ABSTRACT: Retinal degenerative diseases are a leading cause of blindness worldwide. Cell replacement therapy involving photoreceptors integration faces challenges such as survival, axonal elongation, and synapse formation between donor cells and the host retina. In this study, we investigated the impact of small molecules and the cells' microenvironment on neurite extension of rat photoreceptor precursors (PRP). We observed a dose-dependent effect of the RhoA kinase inhibitor (ROCKi), Y-27632, resulting in a significant enhancement in the percentage of cells with neurites and neurite elongation. Additionally, we demonstrated that treatment with the amino acid Taurine and retinal conditioned media (RCM) augmented neurite outgrowth. RNA-seq analysis conducted on PRP cells treated with 50µM Y-27632 revealed upregulation in genes associated with BMP4 and phototransduction pathways. BMP4 inhibitor inhibited neurite extensions in cultures treatment with taurine and RCM, indicating the involvement of these pathways in the extension process. Finally, we explored PRP neurite outgrowth seeded on RCS degenerated organotypic explants to investigate the influence of the 3D microenvironment on neurite extension. Neurite extension was significantly upregulated when seeded on the retinal explant, particularly when seeded in a collagen matrix mimicking the retinal ECM. Our findings highlight the involvement of BMP4 and the phototransduction pathway in PRP neurite elongation and underscore the importance of small molecules and the 3D environment in this process

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE276397 | GEO | 2026/08/24

REPOSITORIES: GEO

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