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Dan-Ning Hu, Richard B Rosen; Protective Effects Of Adrenergic Receptor Agonists On Hydroxychloroquine-Induced Damage in Cultured Human RPE Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1690.
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Long-term usage of hydroxychloroquine (HCQ) for the treatment of autoimmune diseases can lead to HCQ retinopathy. This is largely caused by the inhibition of lysosomal enzyme activity, leading to blockage of autophagy, resulting in the increase of vacuolation and cell death. We hypothesized that various adrenergic receptor agonists (ARG) might exert different protective effects on RPE cells against HCQ damage, and 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, 30, 100 μM with or without various ARG at 10-5 mM for 24 hours. Morphological changes and cell viability were evaluated using phase-contrast microscopy and trypan blue assay. All experiments were performed in triplicate.
RPE cells cultured with 30 μM HCQ showed a marked increase of vacuolation in the cytoplasm (+++). Cells cultured with 100 μM HCQ showed a significant decrease of in cell viability (33.6±2.6)% compared to controls (P<0.05). Methoxamine (α1-), Clonidine (α2-), and CL316243 (β3-) receptor agonists did not improve the cell viability as compared with cell treated with HCQ 100 μM alone (P>0.05) with decreases of (31.0±2.5), (32.2±2.2), and (36.5±3.6)% of the controls, respectively; nor affect the accumulation of vacuolation in cells treated with 30 μM HCQ alone (all at +++).However, Prenalterol (β1-) and Salbutamol (β2-) receptor agonists significantly decreased the vacuolation (+) and improved the cell viability as compared with cell treated with HCQ 100 μM alone [P<0.05 at the level of (64.9±5.1) and (66.6±5.2)% of the controls, respectively].
Adrenergic receptor agonists for β1- and β2- receptors significantly protected RPE cells against HCQ damage, whereas α-1, α-2, and β3-receptor agonists did not.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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