Graduation Year

2020

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Medical Sciences

Major Professor

Manas R. Biswal, M.F.Sc., Ph.D.

Committee Member

Vijaykumar Sutariya, Ph.D., R.Ph.

Committee Member

Nurettin Sahiner, M.Sc., Ph.D.

Keywords

age-related macular degeneration, antioxidants, cellular detoxification, gene therapy, reactive oxygen species

Abstract

Currently, the most widely available treatment for wet age-related macular degeneration (AMD) involves the intraocular delivery of biopharmaceuticals, such as anti-VEGF therapy. Drawbacks of this treatment includes a short-term efficacy, requiring repeated injections with additional risks, and a limited availability of options for non-responders. Furthermore, there are no treatments available for patients diagnosed with dry-AMD. The drawbacks and limitations of current therapies represent a need for more effective and permanent therapy as the prevalence of the population affected by AMD is growing. Antioxidant gene therapies are one solution to these implications, protecting the cells from oxidative stress which is one of the major contributing factors of AMD. It has been found that the retina and retinal pigment epithelium (RPE) affected by AMD shows a reduced expression of Glutathione-S-Transferase Mu 1 (GSTM1), a natural antioxidant defense in the body. To this date, no study has been conducted on the protective effects of GSTM1 overexpression in the RPE from oxidative stress. We hypothesize a GSTM1 antioxidant gene therapy on a human retinal pigment epithelial cell line, ARPE-19, will protect cells from oxidative stress implicated in the pathogenesis of AMD.

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