PhD Scientific Days 2020

Theoretical and Translational II. Posters

Sigma-1 Receptor Agonist Protects Human Trabecular Meshwork Cells from Fibrotic Factors

Előadó neve

Dr. Tran, Ngoc Minh

Előadó munkahelye

Semmeiweis University

Előadó telefonszáma

+36703189952

Előadó e-mail címe

ngocminhdt@gmail.com

Az előadás címe

Sigma-1 Receptor Agonist Protects Human Trabecular Meshwork Cells from Fibrotic Factors

Szerző(k) neve és munkahelye

Minh N. Tran 1,2, Balazs Besztercei 3, Illes Kovacs 4, Xavier Gasull 5, Attila J. Szabo 2,6, Andrea Fekete 1,2, Judit Hodrea 1,2

1. Lendület Diabetes Research Group, Semmelweis University, Budapest
2. 1st Department of Pediatrics, Semmelweis University, Budapest
3. Institute of Clinical Experimental Research, Semmelweis University, Budapest
4. Department of Ophthalmology, Semmelweis University, Budapest
5. Department of Biomedicine, Institute of Neurosciences, University of Barcelona, Barcelona
6. HAS-SU Pediatric and Nephrology Research Group, Semmelweis University, Budapest

Szekció

Theoretical and Translational II. Posters

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Clinical Medicine

Összefoglaló szövege

Introduction
Lowering intraocular pressure (IOP) is currently the only strategy to slow the progression of glaucoma. IOP can be reduced by decreasing the aqueous humor production or increasing its outflow. The fibrotic-like remodeling of the actin cytoskeleton in trabecular meshwork (TM) cells decreases outflow, thus cytoskeletal disrupting drugs could be a novel therapeutic approach to lower IOP.
We showed that fluvoxamine (Flu), the sigma-1 receptor (S1R) agonist, is anti-fibrotic in the kidney, therefore we hypothesize its efficiency in the prevention of fibrotic remodeling in the eye.
Aims
To investigate the expression of S1R in TM cells and to measure the effect of Flu on (i) proliferation and (ii) on actin cytoskeleton rearrangement of control human TM cells (HTM5).
Method
Immunocytochemistry and Western blot were used to detect S1R on HTM5 cells. To investigate the effect of Flu on proliferation, cells were treated for 24h either with 20 ng/mL platelet-derived growth factor (PDGF) or 10 ng/mL transforming growth factor-beta 2 (TGF-β2) combined with 10 or 15 µM of Flu. Cell proliferation was determined by the thiazolyl blue tetrazolium bromide assay. Morphological changes and cytoskeleton rearrangements were visualized by immunostaining of F-actin and were detected with an inverted fluorescent microscope.
Results
S1R is present in HTM5 cells and localized in the cytosol. Cell proliferation induced by PDGF or TGF-β2 was prevented by Flu. Phalloidin staining of HTM5 cells showed a diffuse actin network of thin actin filaments in controls. A change of cytoskeleton morphology was observed upon PDGF or TGF-β2 treatment caused by the reorganization of stress fibers along a longitudinal axis, with the formation of F-actin bundles and actin-clumps. All of these phenomena were largely blocked by Flu.
Conclusion
Flu can reduce the profibrotic factors-induced cytoskeletal rearrangement that may lead to lower outflow resistance thus, enhancing outflow facility. Our preliminary results propose that Flu could be a potential candidate for the development of a novel IOP-lowering drug. However, further experiments with other treatments that alter TM functionality (CTGF or Dexamethasone) are needed to corroborate these results, as well as studies in in vivo animal models.

Additional Information

Supervisor: Judit Hodrea
Email address: judit.hodrea@gmail.com
Grants: VKE-2017-00006, FK124491, FIKP

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4749

Start

13:02

End

13:05

Authors (legacy)

Minh N. Tran 1,2, Balazs Besztercei 3, Illes Kovacs 4, Xavier Gasull 5, Attila J. Szabo 2,6, Andrea Fekete 1,2, Judit Hodrea 1,2

1. Lendület Diabetes Research Group, Semmelweis University, Budapest
2. 1st Department of Pediatrics, Semmelweis University, Budapest
3. Institute of Clinical Experimental Research, Semmelweis University, Budapest
4. Department of Ophthalmology, Semmelweis University, Budapest
5. Department of Biomedicine, Institute of Neurosciences, University of Barcelona, Barcelona
6. HAS-SU Pediatric and Nephrology Research Group, Semmelweis University, Budapest