The maculoprotective effect of a thiol antioxidant in retinal degeneration models

"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 <i>tert</i>-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.

Name thesis:degree_name

Ph. D. in Chemistry

Grantor

Missouri University of Science and Technology

Author dc:creator

• Wang, Hsiu-Jen

• 4-HNE
• Age-Related Macular Degeneration
• Glutathione
• ONL
• Oxidative Stress
• Thiol Antioxidant
• Biochemistry
• Chemistry

Repository record dc:identifier

https://scholarsmine.mst.edu/doctoral_dissertations/2635

OAI identifier oai:identifier

oai:scholarsmine.mst.edu:doctoral_dissertations-3640