Modulation of post‐surgery fibrosis in glaucoma filtration surgery by targeting retinoic acid signaling

Aims/Purpose: Glaucoma filtration surgery (GFS) aims to alleviate intraocular pressure by improving fluid drainage from the eye. However, post‐surgery scarring, particularly around the surgical site, can impede fluid flow and compromise surgical outcomes. Dysregulated inflammatory responses and abnormal extracellular matrix (ECM) remodeling contribute to excessive scarring. Retinoic acid signaling is known to modulate immune responses, ECM remodeling, and fibrosis in various organs. This study seeks to investigate the influence of key retinoic acid signaling components on post‐surgery scarring in the eye.

Methods: Expression levels and patterns of selected retinoic acid signaling pathway components were assessed in conjunctival tissues of C57BL/6 mice undergoing GFS using RT‐PCR and Western blot analysis. Mice with global deletion of specific retinoic acid signaling pathway components underwent GFS to evaluate their role in subconjunctival fibrosis. Inflammatory responses were evaluated by immunofluorescence staining for the pan‐myeloid marker CD11b, and fibrotic tissue was visualized using Masson's trichrome stain. Subconjunctival tissues from knockout and wild‐type littermate controls were analyzed for inflammatory cytokines, chemokines, and fibrotic markers via Western blot analysis.

Results: GFS induced the expression of different components of the retinoic acid signaling pathway in mice. Deletion of specific retinoic acid signaling pathway components resulted in alterations in GFS‐induced recruitment of myeloid cells and ECM remodeling.

Conclusions: Modulating retinoic acid signaling presents a promising approach for controlling post‐surgery fibrosis in the eye, offering an alternative avenue to enhance the outcomes of glaucoma filtration surgery.