Doctoral Dissertations

Author

Hsiu-Jen Wang

Keywords and Phrases

4-HNE; Age-Related Macular Degeneration; Glutathione; ONL; Oxidative Stress; Thiol Antioxidant

Abstract

"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among adults, age 60 and older, in developed countries. While oxidative stress is implicated in the pathogenesis of AMD, clinical studies have shown that dietary antioxidants can delay progression of AMD. Currently, there is no FDA-approved treatment for AMD. Therefore, we hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would protect retinal pigment epithelium and impede the progression of retinal degeneration. The goal of this work was to evaluate the efficacy of NACA in preventing retinal pigment epithelial cell and photoreceptor death in AMD models. To achieve this, we used the oxidants tert-butyl hydroperoxide (TBHP) and sodium iodate (NaIO₃) in a cell model and an animal model to evaluate the effects of NACA. Our data suggest that pretreatment with NACA reduces the sub-lethal (but not lethal) effects of TBHP in primary cultures of human retinal pigment epithelial cells. NACA significantly improves cell survival when administered prior to and during the occurrence of oxidative damage similar to that observed in the development of dry AMD. In the chemically- induced retinal degeneration animal model, NACA eye drops partially prevented reduction in visual function, as determined from electroretinograms (ERG) recorded 36 hours after NaIO3 injection. Other toxic effects were observed at a later time point after NaIO₃ injection: increased lipid peroxidation (as measured by formation of 4-hydroxynonenal, 4-HNE), elevated cysteine levels, and death of photoreceptors resulting in outer nuclear layer thinning. NACA eye drops reversed these toxic effects. In conclusion, this potent antioxidant should continue to be investigated as a treatment for AMD"--Abstract, page iv.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Aronstam, Robert
Kapila, Shubhender
Winiarz, Jeffrey G.
Woelk, Klaus

Department(s)

Chemistry

Degree Name

Ph. D. in Chemistry

Sponsor(s)

National Eye Institute
National Institutes of Health (U.S.)

Publisher

Missouri University of Science and Technology

Publication Date

Fall 2017

Journal article titles appearing in thesis/dissertation

  • The role of N-acetylcysteine amide in defending primary human retinal pigment epithelial cells against tert-butyl hydroperoxide-induced oxidative stress
  • N-acetylcysteine amide (NACA) eye drops partially prevent the loss of visual function and retinal damage in a chemically-induced retinal degeneration animal model

Pagination

xx, 122 pages

Note about bibliography

Includes bibliographic references.

Rights

© 2017 Hsiu-Jen Wang, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Thesis Number

T 11245

Electronic OCLC #

1021857689

Comments

Financial support of National Institutes of Health (U.S.) R15EY022218-01

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