Abstract
Purpose :
Cigarette smoking and oxidative stress have been implicated in the pathogenesis of AMD. Integrins are cell signaling receptors and have been associated with AMD. Anti-integrin therapy is a promising new approach in the treatment of retinal diseases. Herein, we investigate the effect of Luminate, a synthetic oligopeptide that binds to multiple integrin receptor sites, on RPE cell injury induced by hydroquinone (HQ), an important oxidant in cigarette smoke.
Methods :
Cultured human RPE cells were loaded with 20µM CM-H2DCFDA (an indicator for reactive oxygen species (ROS)) and 10µM JC-1 (an indicator of mitochondrial membrane potential, Δψm) for 30 minutes followed by the treatment with HQ at different concentrations in the presence or absence of Luminate (0.4mM, Allegro Ophthalmics, LLC) for a various times. Cell viability was evaluated with WST-1 assay. A fluorescence plate reader was used to quantify ROS production and a ratio of green JC-1 monomer/red JC-1 aggregate, respectively. Mitochondrial respiration was measured by XFe24 analyzer.
Results :
Compared to untreated cells, HQ significantly increased ROS levels (P<0.05), decreased Δψm (P<0.05), decreased cell viability (P<0.05) and decreased mitochondrial bioenergetics (P<0.05). Luminate significantly decreased HQ-induced ROS production (P<0.05), improved HQ-decreased Δψm (P<0.05), decreased HQ-induced cell death (P<0.05) and prevented HQ-decreased mitochondrial bioenergetics (P<0.05) when compared to HQ-treated cells.
Conclusions :
Luminate protects RPE cells against HQ-induced injury and restores mitochondrial function. Our data suggest a potential role for Luminate therapy in the prevention of retinal diseases, such as AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.