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Dan-Ning Hu, Ruihuo Zhang, Richard B Rosen; Protective effects of dopaminergic agonists on hydroxychloroquine-induced damage in cultured human RPE cells . Invest. Ophthalmol. Vis. Sci. 2020;61(7):4953.
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Treatment of autoimmune diseases with long-term usage of hydroxychloroquine (HCQ) can lead to HCQ retinopathy. This is mainly caused by the decrease of lysosomal enzyme activity, which leads to blockage of autophagy, resulting in the increase of vacuolation and cell death. We hypothesized that various dopaminergic agonists (DA) might protect RPE cells against HCQ damage based upon their ability to increase cAMP levels, and have used our in vitro model to test this hypothesis.
Cultured human RPE cells isolated from donor eyes were seeded into 24-well plates and treated with HCQ at 0 (negative control), 30 and 100 μM (positive control) with or without various DA at 10-5 mM for 24 hours. Morphological changes and cell viability were evaluated using phase-contrast microscopy and a dye-exclusion assay. All experiments were performed in triplicate.
RPE cells cultured with 30 μM HCQ showed a marked increase of vacuolation in the cytoplasm (+++) and those cultured with 100 μM HCQ showed a significant decrease of cell viability, (34.1±1.5)% of controls (P=0.001 compared to the controls). Both DR1/5 agonists (SKF81297 and A77636) significantly decreased the vacuolation (+) and SKF81297 improved the cell viability to (58.7±4.5)% of controls (P=0.002, compared with cells treated with HCQ 100 μM alone). Quinpirole (DR2) and PD-168077 (DR4) agonists neither decreased the vacuolation (+++), nor improved the cell viability, (37.7±2.0)% and (34.4±1.0)% of controls, respectively (P=0.98 and 0.84 as compared with the positive controls). Non-specific DA (apomorphine) only slightly decreased the vacuolation (++) and improved cell viability (38.7±2.4)% (P=0.049 compared with the positive controls).
DR1/5 agonists, which are known cAMP elevators, protect RPE cells against HCQ damage; whereas DR2-4 agonists that do not elevate the cAMP levels, have no protective effect.
This is a 2020 ARVO Annual Meeting abstract.
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