Proteomic Insights into the Retinal Response to PRGF in a Mouse Model of Age-Related Macular Degeneration

<i>Background and Objectives</i>: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. <i>Materials and Methods</i>: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO₃ administration. Animals were divided into three groups: Control (PBS), Disease (NaIO₃ + PBS), and PRGF-treated (NaIO₃ + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. <i>Results</i>: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO₃-induced retinal damage. <i>Conclusions</i>: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO₃ by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression.