An estimated 170.38 million elderly adults suffer from some stage of age-related macular degeneration (AMD) worldwide, a vision defect that damages the macula, the central region of the retina required for sharp vision, such as reading, driving, and recognizing faces. Genetic factors strongly modify one's risk for developing AMD, and most of these genetic changes are found in genes of the alternative complement cascade, a component of the immune system. The lack of effective AMD prevention calls for the identification of druggable molecules and pathways.
In my research, I use microarrays and RNA sequencing to investigate the events occurring in early AMD, the reasons for macular susceptibility to AMD, and the events triggering aberrant blood vessel growth in late AMD. First, I found that genes associated with endothelial cells tend to be expressed at lower levels in human donors eyes affected by early AMD than in control eyes, concordant with previous studies indicating loss of choriocapillaris in early AMD. Second, I found that molecular signals across regions of the retina, retinal pigment epithelium, and choroid generally mirror the distribution of cell types in these regions. Third, I found that damage to cultured primate chorioretinal endothelial cells by the end product of complement activation, membrane attack complex, produces an environment conducive to choroidal neovascularization, a symptom of late-stage AMD. I propose a model that bridges genetic variants in the complement cascade genes with blood vessel loss in early AMD and the pathological growth of blood vessels in late AMD.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-5850 |
| Date | 01 May 2015 |
| Creators | Whitmore, Steven Scott |
| Contributors | Mullins, Robert F., Scheetz, Todd E. |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | dissertation |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright © 2015 Steven Scott Whitmore |
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