PhD Scientific Days 2025

Pharmaceutical Sciences and Health Technologies IV.

Age-specific anti-glaucomatous effect of a Fluvoxamine-containing eye drop

Name of the presenter

Medveczki Timea

Institute/workplace of the presenter

MTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, Budapest

Authors

Tímea Medveczki¹, Minh N. Tran¹, Anna Takacsi-Nagy², Tamas Lakat¹, Akos Toth¹, Illes Kovacs³, Gyorgy Torok⁴, Attila J. Szabo⁵, Andrea Fekete¹, Judit Hodrea¹

1: MTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, Budapest
2: PannonPharma Pharmaceutical Ltd, Pécsvárad
3: Department of Ophthalmology, Semmelweis University, Budapest
4: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest
5: Pediatric Center, MTA Centre of Excellence, Semmelweis University, Budapest

Text of the abstract

Introduction
The Sigma-1 receptor (S1R) is a multifunctional chaperone involved in cellular stress responses and neuroprotection with emerging roles in ocular health. Aging is a major risk factor for glaucoma, the second leading cause of blindness worldwide, currently affecting 80 million people. Elevated intraocular pressure (IOP), often driven by age-related trabecular meshwork (TM) fibrosis, impairs aqueous humor outflow. Current therapies have limited efficacy and side effects. Our prior work showed that S1R activation reduces TM fibrosis. Based on these findings, we developed a fluvoxamine (FLU)-containing eye drop, a known S1R agonist, and confirmed its ocular safety.
Aims
To evaluate the IOP-lowering and anti-fibrotic effects of FLU eye drops in aged mice and examine age-related transcriptional changes in primary TM cells.
Methods
In vivo: Glaucoma was induced in 6–8-month-old wild-type and S1R knockout C57BL/6J mice using dexamethasone. Mice were treated with vehicle or FLU eye drops twice daily for two weeks. IOP was measured weekly over four weeks.
In vitro: Primary TM cells from 10-week, 6-month, and 2-year-old mice were isolated. After TGF-β2 and TNF-α stimulation, expression of extracellular matrix proteins and inflammatory cytokines were assessed.
Results
FLU eye drops lowered IOP by ~10% (from 18.69 to 16.97 mmHg) in wild-type but not in S1R knockout mice, confirming S1R’s role. TM cells from aged mice showed increased F-actin and fibronectin levels. FLU reduced TGF-β2-induced F-actin accumulation and TNF-α-induced IL-6 expression in aged primary TM cells.
Conclusion
FLU eye drops effectively, and S1R specifically reduce IOP, supporting the potential therapeutic role of S1R agonists in glaucoma. Our in vitro findings further suggest that fibrotic processes contributing to glaucoma are more pronounced with aging and that the effects of S1R agonists may be age-dependent.
Funding
LP2021-3/2021, TKP2021-EGA-24, STAGE 2024-1.2.3-HU-RIZONT-2024-00056,SigmaDrugs Research. „SUPPORTED BY THE 2.1.1-2024-00004 UNIVERSITY SCHOLARSHIP PROGRAMME OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND.”