Graduation Date

5-2014

Document Type

Master's Thesis

Degree Name

Master of Science

Department or Program

Biological Sciences

Department or Program Chair

Mary Sevigny, PhD

First Reader

Deepak Lamba, MBBS, PhD

Second Reader

Mohammed El Majdoubi, PhD

Abstract

Age-related macular degeneration is a debilitating condition that manifests as a loss of the central portion of an individual’s field of vision, affecting 1 in 3 people over the age of 80. With regards to the retina, the organ primarily responsible for an individual’s sense of vision, this condition is associated with the degeneration of the central point in the retina, known as the macula, which contains the highest concentration of light-sensitive photoreceptors. It is currently known that the human retina exhibits a gradual decrease in protective detoxifying factors such as glutathione-S-transferase-1 and catalase as well as increased lipid peroxidation, all of which resulting in the age-related increase in autofluorescent lipofuscin between the retina and the choroid. This prevents the proper deliverance of nutrients to the foundational layer of cells in the retina, leading to oxidative stress-related apoptosis of first the retinal pigmented epithelium (RPE) and then the photoreceptors. MicroRNAs (miRNAs) are a group of endogenous noncoding RNA molecules that originate from parts of the genome that were originally speculated to be “junk” DNA. However, it is now known that these small RNA molecules are responsible for gene silencing on the post-transcriptional level via the degradation or transcription inhibition of specific mRNA transcripts. In the context of age-related macular degeneration, certain miRNAs may be upregulated to induce the downregulation of apoptotic genes. On the other hand, certain miRNAs is may become downregulated to promote enhanced expression of protective factors. We hypothesize that miRNAs play a role in regulating oxidative response of RPE cells, which may then contribute to cell survival by the upregulation of endogenous pro-survival antioxidant elements.

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