Date on Master's Thesis/Doctoral Dissertation

5-2022

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Song Zhao-Hui

Committee Member

Tamiya, Shigeo

Committee Member

Hein, David

Author's Keywords

Endocannabinoid system; fibrosis; TGFbeta; retinal fibrosis; N-oleoyl dopamine

Abstract

Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction of collagen matrices by porcine RPE cells in a concentration-dependent manner, with significant inhibition of contraction observed with ³3 μM. OLDA did not significantly affect proliferation of porcine RPE cells. Further investigations showed that treatment with 3 μM OLDA significantly decreased TGF-β2-induced α-SMA incorporated stress fibers and total α-SMA protein expression. Taken together these results indicate that OLDA has potential to inhibit TGF-β induced fibrosis in the retina. Further studies are warranted to investigate the mechanism of action, other fibrotic end points, as well as potential in vivo.

Available for download on Monday, November 14, 2022

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