A Pilot Study Profiling Aqueous Humor-Derived Exosomal MicroRNA in Primary Open-Angle and Exfoliation Glaucoma

초록

Objective: To profile aqueous humor (AH)-derived exosomal microRNAs (miRNAs) in primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG) and investigate their potential as diagnostic biomarkers and modulators of extracellular matrix (ECM) remodeling in glaucoma pathogenesis. Design: Prospective, comparative, observational pilot study. Subjects and Controls: Aqueous humor was obtained from 21 patients with POAG, 24 patients with XFG, and 14 healthy donors. Methods: Exosomes were isolated from pooled AH samples of patients with POAG, XFG, and healthy donors for small RNA sequencing. miR-29a, an ECM-targeting miRNA, was selected for functional validation in transforming growth factor-beta 2 (TGF-(32)- or dexamethasone (Dex)-induced collagen deposition models using human trabecular meshwork cells (HTMCs). Main Outcome Measures: Identification of potential glaucoma-and subtype-specific exosomal miRNA biomarkers and evaluation of selected ECM-targeting miRNAs for their roles in modulating collagen expression in vitro. Results: A total of 130 and 145 miRNAs were differentially expressed in POAG/Healthy and XFG/Healthy comparisons, respectively, with 96 miRNAs commonly dysregulated. Upregulation of ECM-related miRNAs & horbar;miR-21-5p, miR-92b-3p, miR-99a-5p, miR-486-3p, miR-486-5p, and miR-1260a & horbar;constituted a glaucoma-specific signature, whereas miR-99b-5p and miR-125a-5p showed subtype-specific upregulation in POAG, and miR-26a-5p and miR-451a in XFG. miR-29a-3p, a known antifibrotic miRNA, was significantly downregulated in POAG, XFG, and in HTMCs treated with TGF-(32 or Dex. Functional assays demonstrated that overexpression of miR-29a-3p attenuated TGF-(32-and Dex-induced collagen deposition in HTMCs. Conclusions: This study provides the first profile of AH-derived exosomal miRNAs in POAG and XFG, identifies potential miRNAs associated with ECM remodeling, and highlights their potential utility as biomarkers and therapeutic targets in glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2026;6:100996 (c) 2025 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

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