PhD Scientific Days 2026

Poster Session 2.B - Molecular Medicine

Fluvoxamine-mediated Sigma-1 receptor Activation Suppresses TGF-β2 and PDGF-induced Corneal Fibroblast Activation and Extracellular Matrix Remodeling

Name of the presenter

Buzogány, Zsuzsanna

Institute/workplace of the presenter

Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest

Authors

Zsuzsanna Buzogany¹, Judit Hodrea¹, Illes Kovacs², Attila J. Szabo¹, Andrea Fekete¹
1: Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest
2: Department of Ophthalmology, Semmelweis University, Budapest

Text of the abstract

Introduction:
Corneal fibrosis, a major cause of vision impairment and blindness in diabetes and external injuries, is driven by TGF-β and PDGF-mediated myofibroblast activation. We previously showed that the Sigma-1 receptor (S1R) agonist fluvoxamine (FLU) reduces fibrotic damage in the trabecular meshwork. S1R’s pharmacological activation represents a promising, yet unexplored therapeutic strategy to mitigate the fibrotic cascade in the corneal stroma.
Aims:
To elucidate the effects of FLU on TGF-β and PDGF-driven fibroblast activation, focusing on proliferation, extracellular matrix (ECM) remodeling, and the expression profile of key fibrotic markers at both mRNA and protein levels.
Methods:
Primary human corneal fibroblasts were isolated enzymatically and cultured in DMEM:F12 with 10% FBS. Cells were treated with TGF-β2 or PDGF ± FLU (10 µM) for 48–72 h. Viability and proliferation were assessed by MTT/LDH; α-SMA, F-actin, Ki67, and Fibronectin by immunocytochemistry; and Col1A1, FN, CTGF, MMP9, and S1R by qPCR or Western blot.
Results:
FLU and PDGF were non-toxic within the tested concentration ranges. FLU increased S1R expression and reduced α-SMA, Fibronectin, MMP9, Col1A1, and CTGF levels, indicating suppression of fibroblast activation and ECM remodeling.
Conclusion:
FLU attenuates TGF-β2 and PDGF-driven fibroblast activation and promotes S1R expression, supporting its potential as a novel anti-fibrotic candidate in corneal wound healing.
Funding:
OTKA-K135398, LP2021-3/2021, TKP2021-EGA-24, 2023-2.1.2-KDP-2023-00016, STAGE 2024-1.2.3-HU-RIZONT-2024-00056
zsuzsi.buzogany@gmail.com
Semmelweis University
Prof. Fekete Andrea

Oral presentation