PhD Scientific Days 2026

Molecular Medicine 1.

The Sigma-1 Receptor Agonist Fluvoxamine Is Protective in Hyperglycaemia-Induced Dysfunction of Trabecular Meshwork Cells

Előadó neve

Ms. Rózsahegyi, Alexandra

Neptune code

E1AXM0

Előadó munkahelye

Semmelweis University, Pediatric Center, Bókay Street

Előadó telefonszáma

06307231000

Előadó e-mail címe

rozsahegyi.alexandra@phd.semmelweis.hu

Az előadás címe

The Sigma-1 Receptor Agonist Fluvoxamine Is Protective in Hyperglycaemia-Induced Dysfunction of Trabecular Meshwork Cells

Szerző(k) neve és munkahelye

Alexandra Rozsahegyi^1,2, Marcell Cserhalmi¹, Timea Medveczki^1,2, Zsuzsanna Buzogany^1,2, Eva Ruisanchez^3,4, Andras Budai⁵, Balazs Besztercei³, Attila J Szabo², Judit Hodrea^1,2, Andrea Fekete^1,2

1: MTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, Hungary;
2: Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary;
3: Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary;
4: HUN-REN-SU Cerebrovascular and Neurocognitive Disorders Research Group, 1094 Budapest, Hungary
5: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Molecular Medicine 1.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction and aims: Diabetes mellitus (DM) is associated with a doubled prevalence of elevated intraocular pressure (IOP) caused by trabecular meshwork (TM) dysfunction. Chronic hyperglycaemia leads to oxidative stress and fibrotic remodeling of the TM. We previously identified the Sigma-1 receptor (S1R) as a novel anti-fibrotic target by demonstrating that its agonist, fluvoxamine (FLU), is protective in diabetes-related renal fibrosis. Here, we investigate its potential to mitigate ocular fibrosis.
Methods: First, we wanted to verify in different in vivo models (high-fat diet/streptozotocin (HFD/STZ) rats, db/db mice) that type 2 DM (T2DM) leads to fibrotic remodeling of the TM. Then, in vitro, we assessed the effect of FLU (15 μM) on hyperglycaemia-induced (HG, 25 μM) fibrosis, oxidative stress, and endogenous nitric oxide (NO) production.
Results: In T2DM models, excessive accumulation of collagen, α-smooth muscle actin (αSMA), fibronectin (Fn), and F-actin was observed in the eyes. Ocular fibrosis was accompanied by IOP elevation (13.7 vs. 18.7 mmHg) in db/db mice. In human TM cells (HTM5), FLU decreased HG-induced cell proliferation (14% vs. 24%) and upregulated S1R protein expression. Furthermore, FLU suppressed the expression of key fibrotic elements, including transforming growth factor-β2 (TGF-β2) by 37%, Fn by 49%, collagen type 1 (COL1A1), and type 4 (COL4A1) by 24% and 45%, respectively. FLU also reversed HG induced F-actin accumulation by 39% and enhanced intracellular NO levels by 34%. Crucially, FLU decreased ROS generation by half, demonstrating its protective effect against HG-induced oxidative stress.
Conclusion: These findings highlight the potential of S1R activation as a promising therapeutic target to alleviate hyperglycaemia-induced injury to the TM by modulating multiple molecular pathways.
Funding: TKP2021-EGA-24, STAGE 2024—1.2.3-HU-RIZONT-2024-00056, LP2021-3/2021

University

Semmelweis University

Supervisor

Prof. Andrea Fekete

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

9078

Start

10:15

End

10:25