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

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.

Prospective, comparative, observational pilot study.

Aqueous humor was obtained from 21 patients with POAG, 24 patients with XFG, and 14 healthy donors.

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-β2)- or dexamethasone (Dex)-induced collagen deposition models using human trabecular meshwork cells (HTMCs).

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.

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-miR-21-5p, miR-92b-3p, miR-99a-5p, miR-486-3p, miR-486-5p, and miR-1260a-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-β2 or Dex. Functional assays demonstrated that overexpression of miR-29a-3p attenuated TGF-β2- and Dex-induced collagen deposition in HTMCs.

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.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.