Honors Capstone Project
Date of Submission
Arts and Science
Retinitis pigmentosa, toretinal gliosis
Capstone Prize Winner
Won Capstone Funding
Sciences and Engineering
Biotechnology | Integrative Biology
More than 30 million Americans are blind or visually impaired due to injury or disease. Retinitis pigmentosa is a genetic disease that initially causes death of rod photoreceptor cells and is followed by the progressive degeneration of the retina, the light sensing tissue of the eye, ultimately leading to blindness. Retinitis pigmentosa leads toretinal gliosis, a process in which a specialized neuroglial cell that is specific to the retina, known as Müller glia, undergoes hypertrophy and migration as a reaction to retinal stress or damage. I am investigating the mechanisms that are responsible for this type of degeneration in the African clawed frog (Xenopus laevis), as well as those that allow regeneration of the rod photoreceptor cells in this model organism. Intermediate filament proteins (IFPs) are hypothesized to contribute to progressive retinal degeneration and may inhibit retinal regeneration. IFPs are cytoskeletal components of cells responsible for structural and mechanical support, and are thought to be upregulated during a process known as gliosis. Genomic analysis of the Xenopus genome has led to the hypothesis that this species does not contain the gene for one of the class III IFPs known as Glial Fibrillary Acidic Protein (GFAP). Therefore, degeneration may be regulated by one of the other class III and IV IFPs including Vimentin (Vim), Peripherin (Prph), Desmin (Des), and -Internexin (Ina). Using immunohistochemistry and in situ hybridization, I examined the expression patterns of IFPs to determine where the proteins and corresponding mRNA localize in the retina and brain. I found that two GFAP antibodies used in previous publications have distinct expression patterns in Xenopus retina. Additionally, I found that three of the five class III IFPs are expressed in the retina. Since GFAP is not present in the Xenopus genome, the results suggest that the GFAP antibodies must be nonspecific. Given the high level of sequence similarity among the IFPs, and their response to retinal injury, the IFPs Vimentin and Peripherin may be the immunogens detected by the anti-GFAP antibodies used in previous publications. Since gliosis and progressive retinal degeneration are observed in Xenopus following retinal injury, future research should investigate the expression patterns of these IFPs in injured retinas using a controllable ablation model.
Aruck, Alexandria, "The Role of Intermediate Filament Proteins in Retinal Degeneration and Regeneration" (2016). Honors Capstone Projects - All. 919.
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