Acquired retinal diseases such as proliferative diabetic retinopathy and age-related macular degeneration pose significant challenges in diagnosis and prognosis. The vitreous fluid, situated in the posterior chamber of the eye behind the lens, holds a close relationship with the inner retina. Within this milieu, retinal cells secrete a diverse array of biomolecules, potentially harboring vital biomarkers. Among these, short, non-coding micro-RNAs (miRNAs) emerge as promising candidates. Their dynamic regulation by various gene signaling mechanisms, enhanced resistance to degradation, and secretion via separate exocytotic pathways make them particularly significant. Alterations in vitreal miRNA profiles may reflect pathological states and offer insights into disease etiology and progression. We conducted a comprehensive meta-analysis of 22 peer-reviewed studies to assess the potential of vitreous miRNAs as biomarkers for retinal diseases. Our analysis demonstrates the potential utility of miRNAs as biomarkers in specific retinal pathologies. We show that miR-142, miR-9, and miR-21 emerge as robust biomarker candidates, displaying consistent and significant alterations correlating with proliferative vitreoretinal diseases. We also address the methodological challenges encountered in characterizing vitreous miRNA content, including the absence of standardized purification, amplification, and analysis protocols, as well as the scarcity of true control samples. Moreover, we make the case for the adoption of specific housekeeping genes and data normalization techniques to standardize miRNA analysis in the vitreous and explore potential methodologies for obtaining vitreous samples from healthy individuals. Vitreous miRNAs hold promise as potential biomarkers for various retinal diseases, with miR-142, miR-9, and miR-21 emerging as particularly promising candidates. Enhancing methodologies for vitreous sampling and miRNA analysis presents an opportunity to expand the repertoire and utility of miRNA biomarkers in retinal disease diagnosis and prognosis.

The authors have declared no competing interest.

This study was supported by Research to Prevent Blindness (RPB) Career Development Award to MT and RPB Unrestricted Gift to the Flaum Eye Institute, University of Rochester Medical Center.

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This study is a meta-analysis and review of published results. All data used here were previously pulished in peer-reviewed studies and are publicly and freely available.

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