Sonali Nashine
Gavin Herbert Eye Institute, USA
Title: Protective effects of a mitochondrial-derived peptide in a macular degeneration model; implications for therapeutics.
Biography
Biography: Sonali Nashine
Abstract
STATEMENT OF THE PROBLEM: Age-related macular degeneration (AMD), a leading retinal degenerative disease, is a primary cause of irreversible blindness among the elderly population in the United States. AMD ranks third among the global causes of visual impairment and has been listed under the category of priority eye diseases. Dry AMD which manifests as geographic atrophy affects approximately 80-90% of the patients and currently has no available treatments. Therefore, we are in need of treatment strategies for dry AMD. Mitochondrial dysfunction and the subsequent loss of retinal pigment epithelial (RPE) cells have been associated with the development and pathogenesis of AMD. Herein, we hypothesized that a mitochondrial-derived peptide called SHLP2, which is coded from the 16S rRNA gene of the mtDNA, is protective against loss of RPE in AMD cybrid cells.
METHODOLOGY & THEORETICAL ORIENTATION: To prove our hypothesis, we used a series of cell based assays, quantitative RT-PCR, Western blotting, and immunocytochemistry. As an in vitro macular degeneration model, we used ARPE-19 transmitochondrial cybrid cells. All cells were treated with pre-optimized concentrations of SHLP2. Untreated cybrids served as controls.
FINDINGS: Our results revealed that: 1) SHLP2 administration significantly improved mitochondrial function as represented by an increase in the levels of mitochondrial oxidative phosphorylation complex proteins i.e., Complex I (NADH dehydrogenase), Complex II (Succinate dehydrogenase), Complex III (CoQH2-cytochrome c reductase), Complex IV (cytochrome c oxidase), and Complex V (ATP Synthase) in AMD cybrids, and 2) Pretreatment with SHLP2 improved cell viability and preserved mitochondrial number and function in AMD cybrids.
CONCLUSION & SIGNIFICANCE: In conclusion, this novel study identified SHLP2 as a rescue factor that preserved cellular and mitochondrial health in an in vitro macular degeneration model. Our findings are significant because they demonstrated that SHLP2 could be a potential therapeutic target for the treatment of dry AMD. Further studies are needed to establish the potential of SHLP2 as a mitochondria-targeting treatment option for dry AMD.