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 Co-Chair (if applicable)

Tamiya, Shigeo

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.

Additional Files
Lucy Sloan_Signature Page.pdf (86 kB)
Lucy Sloan_Embargo.pdf (268 kB)
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