Theoretical and Translational III. Posters
Szabó, Adrienn, MSc
1st Dept. of Pediatrics, Semmelweis University
+36(20)461-5158
szabo.adrienne93@gmail.com
Protective Role of Sigma-1 Receptor in Corneal Fibrosis
Adrienn Szabo (1,2), Lilla Lenart (1,2), Judit Hodrea (1,2), Balazs Besztercei (3), Illes Kovacs (4), Attila J. Szabo (2,5), Andrea Fekete (1,2)
1 MTA-SE Lendület Diabetes Research Group, Budapest
2 SE 1st Department of Paediatrics, Budapest
3 Institute of Clinical Experimental Research, Semmelweis University, Budapest
4 SE Department of Ophthalmology, Budapest
5 MTA-SE Pediatrics and Nephrology Research Group, Budapest
Theoretical and Translational III. Posters
Hungarian
Theoretical and Translational Medicine
Molecular Sciences
Introduction
Corneal scarring is a pivotal cause of visual impairment, which accounts for over 4% of blindness worldwide with 2 million cases each year. Scarring of the corneal tissue, also known as fibrosis, commonly occurs after infection, postsurgical complications, and response to injury or metabolic disease. Corneal fibrosis is characterized by the presence of myofibroblasts and deposition of extracellular matrix components. Currently, treatment options for cornea scarring are limited and the only effective treatment is corneal transplantation.
Our research group proved that activation of Sigma-1 receptor (S1R) by fluvoxamine (Flu) has antifibrotic effect in the kidney and lung, therefore we hypothesize that Flu could have a protective role in the prevention of fibrosis in the cornea as well.
Aims
To optimize the methods and culturing techniques of primary fibroblast cells from the cornea. To detect the presence of S1R in primary corneal fibroblasts and to measure the effect of Flu on platelet-derived growth factor (PDGF-BB) or transforming growth factor-beta1 (TGF-β1) -induced proliferation and migration of corneal fibroblast cells.
Methods
Cells were treated with PDGF-BB or TGF-β1 to induce fibrotic process. S1R (localization), F-actin and α-SMA (for morphological changes/cytoskeleton rearrangements) were detected by immunofluorescence staining. Cell proliferation was evaluated by thiazolyl blue tetrazolium bromide (MTT) method. Cell migration were followed by wound healing assay.
Results
Primary corneal fibroblast cell culturing method was optimized in three species (human, rat and mouse). S1R is localized in the cytosol of corneal fibroblast cells. PDGF-BB and TGF-β1 increased the proliferation and migration of corneal fibroblast cells and promoted the transformation of fibroblasts to myofibroblasts. These effects were inhibited by Flu.
Conclusion
Flu reduces cytoskeletal rearrangement, myofibroblast transformation and migration, indicating its antifibrotic properties. Our preliminary results propose that Flu could be a potential candidate for development of a novel drug reducing fibrosis in the cornea. However, further molecular experiments (such as investigating inflammatory and apoptotic pathways) and in vivo animal models are needed to reinforce these results.
Grants: NNOTKA-114607, VKE-2017-00006, FK124491
Supervisor: Lilla Lenart
E-mail address: lenart.lillaa@gmail.com
Szóbeli
Szabad
elfogadva
poszter
nem rendelkezett róla
4758
11:10
11:13
Adrienn Szabo (1,2), Lilla Lenart (1,2), Judit Hodrea (1,2), Balazs Besztercei (3), Illes Kovacs (4), Attila J. Szabo (2,5), Andrea Fekete (1,2)
1 MTA-SE Lendület Diabetes Research Group, Budapest
2 SE 1st Department of Paediatrics, Budapest
3 Institute of Clinical Experimental Research, Semmelweis University, Budapest
4 SE Department of Ophthalmology, Budapest
5 MTA-SE Pediatrics and Nephrology Research Group, Budapest