Adam Shaaeli

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. AMD is characterized by the death of retinal pigment epithelium (RPE), likely a result of increased oxidative stress and mitochondrial dysfunction. The purpose of this study is to determine how RPE’s inability to maintain a healthy population of mitochondria contributes to AMD pathology. We hypothesize that defects in mitochondrial fission and fusion lead to an accumulation of damaged mitochondria in AMD RPE. To investigate that, RPE cells were treated with 5uM FCCP (Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone) to stimulate fission by inducing mitochondrial stress. Quantitative analysis for protein expression levels (western blots) and gene expression levels (qPCR) of proteins involved in the fission machinery (FIS1, DRP1, MFF) and the fusion machinery (MFN1, MFN2, OPA1) were conducted at two different time points (4 and 24 hours after treatment). RPE was harvest from donors with AMD and No AMD. Results for protein abundance levels show proteins involved in fission machinery decrease over time while proteins involved in fusion machinery increase over time. Both FIS1 and MFN1 were expressed at significantly higher levels when comparing AMD to No AMD. While these results support our aforementioned hypothesis, more in-depth investigation will be required to draw a more conclusive conclusion.