All ETDs from UAB

Advisory Committee Chair

Stephen Barnes

Advisory Committee Members

Shannon M Bailey

Michelle V Fanucchi

Om P Srivastava

Document Type

Thesis

Date of Award

2012

Degree Name by School

Master of Science in Public Health (MSPH) School of Public Health

Abstract

The ocular lens functions to focus light coming into the eye onto the retina. Lens development begins in utero, and continues over an individual's lifetime. Lens fiber cells and their proteins are only synthesized once and have no repair mechanisms, so they remain for an individual's lifetime. The α-crystallins, the most abundant lens proteins, act as chaperones to keep damaged/unfolded proteins in-solution. Cataract disease is associated with protein damage, leading to a light scattering opacity. It has been suggested that truncation of αA-crystallin leads to a loss of chaperone function. Cataract disease is the leading cause of blindness in the world. Currently, the only treatment is surgical lens replacement, which is not readily available in many developing countries. This has lead to research into potential anti-oxidative compounds, which could be dietary supplemented to slow/prevent cataracts. A previous study in our lab examined dietary supplementation of the soy isoflavone genistein on cataracts in the ICR/f rat. It was found that genistein supplementation accelerated the early stages of cataractogenesis. The goal of this present study was to use MALDI-TOF mass spectrometry imaging and nanoLC-MRM-MS/MS relative quantitation to examine changes in the distribution/localization and relative abundance of five C-terminal truncations (residues 151, 156, 157, 163, and 168) and the full-length form of the αA-crystallin within ICR/f rats from the genistein study. MALDI-MSI data showed the 1-151 truncation to localize within the outer nuclear region of the lens, while the other truncations localized to the inner cortical region, with the full-length protein being limited to the very outer cortical region. There were no observable differences in localization/distribution from genistein supplementation. Relative quantitation showed the 1-151 truncation as the most abundant species, with the 156 and 157 truncations being least abundant, and a significant amount of the full-length species present. There were slight differences in abundance with genistein supplementation, however, the changes were not sufficient enough to be considered significant. Overall, genistein supplementation did not affect the localization/distribution or relative abundance of these truncated species, or the full-length αA-crystallin, suggesting that they did not have a role in the acceleration of cataratogenesis caused with supplementation.

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