Graduation Year

2021

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Graduate School

Major Professor

Manas R. Biswal, Ph.D.

Committee Member

Mark Kindy, MSc, Ph.D.

Committee Member

Christopher Passaglia, Ph.D.

Committee Member

Radouil Tzekov, Ph.D.

Keywords

ERG, OCT, Oxidative Stress, RPE, Sod2

Abstract

MnSod (Sod2) deletion in the retinal pigment epithelium (RPE) of Sod2flox/floxVMD2-cre mice leads to oxidative stress-induced apoptosis of the RPE and photoreceptor cells that show salient features of dry-AMD. The purpose of this study was to investigate the potential antioxidant effect of betaine in protecting retinal health in Sod2flox/floxVMD2-cre mice. Betaine low dose (50mg/Kg Body Weight) and high dose (500mg/kg Body Weight, n=9) were administered intraperitoneally to 8-weeks old male and female Sod2flox/floxVMD2-cre mice daily for four months, while the control group (Sod2flox/floxVMD2-cre mice; n=9) received saline. We used spectral-domain optical coherence tomography (SD-OCT), retinal outer nuclear layer (ONL) thickness measurement, and electroretinography (ERG) to assess retinal function and structure. Furthermore, we determined angiogenic effects by using fundus fluorescein angiography (FFA) and performed hematoxylin and eosin (H&E) staining to analyze retina morphology changes. Our preliminary data showed significant restoration of ERG a-wave and b-wave in the low-dose group compared to the control group following five months of systemic delivery. At the same time, there was no improvement in ERG function in the high-dose group. These results suggest protection of RPE function in betaine the low dose group. OCT measurement in the group treated with betaine low dose demonstrated no significant difference in ONL thickness compared to the control groups before and after 5 months. FFA indicated no presence angiogenic of effect and no significant changes in retina morphology in H&E staining. Future studies are required to evaluate antioxidant gene changes and retinal structural changes in response to betaine treatment. We conclude that daily betaine administration could have a beneficial effect in protecting RPE oxidative stress-induced changes and might provide a therapeutic effect in alleviating Dry-AMD pathophysiology.

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