Protection of Retinal Cells from Light-Induced Apoptosis

Overview

atRAL, a cytotoxic byproduct of the visual cycle, is removed from the eyes’ photoreceptors by ATP-binding cassette transporter (ABCA4), which transports atRAL from the disc lumen to the cytoplasm. Inhibiting mutations in ABCA4 result in a buildup of atRAL, causing disturbances in visual function and leading to apoptosis-based retinal degeneration, seen in Stargardt’s disease, cone-rod dystrophy, and recessive retinitis pigmentosa. This degeneration is mediated by Bax, a pro-apoptotic protein, which is activated by atRAL. The present study aimed to prevent the atRAL-induced retinal cell apoptosis by using newly discovered Bax inhibitors BBI-2 and BBI-4 and ARPE19 cells (human retinal cells) as a model. Baseline death rates of 0.77%±0.15 and 1.81%±0.09 were found for control groups and 30%±5.23 and 33.87%±3.08 for groups treated with 10μM atRAL. Cells treated with BBI-2 and 10μM atRAL had a death rate of 25.8%±2.83, 25.3%±1.82, and 23%±3.33 for three different dosages of BBI-2. Cells treated with BBI-4 and 10μM atRAL experienced a death rate of 20.4%±0.38, 20.1%±1.98, and 13.3%±0.61 for three different dosages of BBI-4. In a second test group, cells treated with BBI-4 and 10μM atRAL had a death rate of 23.58%±2.57 and 19.6%±4.08 for two different dosages of BBI-4. In summary, these results indicate that atRAL-induced retinal cell apoptosis can be reduced by BBI-based selective Bax inhibition. Because atRAL-induced apoptosis is associated with retinal degeneration, this study also provides evidence that BBI-based treatment leads to prevent retinal degeneration, which holds exciting potential for future research into helping prevent cell death and tissue degeneration.

Competition history

• AJAS 2019 Category not listed

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