Ruihua Zhang
Eye and Vision Research Institute, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York 10029, USADan-Ning Hu
Eye and Vision Research Institute, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York 10003, USARichard Rosen
Eye and Vision Research Institute, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York 10003, USARichard Rosen. Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, 310 East 14 Street, Suite 319SB, New York 10003, USA. rrosen@nyee.edu
AIM: To test our hypothesis that activation of protein kinase A (PKA) signal pathway by β-adrenergic agonist plays an important role in the protecting of cultured retinal pigment epithelial (RPE) cells against the hydroxychloroquine (HCQ) toxicity. METHODS: Cultured human RPE cells were treated with 1) HCQ, 2) HCQ with salbutamol (a β2-adrenergic receptor agonist), and 3) HCQ with salbutamol and a PKA inhibitor, and compared these to 4) untreated cells (controls). After treated for 24h, cell vacuolation, cells viability, PKA and PKA kinase activity levels were determined by the measurement of the size of vacuoles using Image J software, the cell counting with a dye-exclusion testing, Western blot and PKA kinase detection, respectively. RESULTS: Cell vacuolation and cell death of cultured RPE cells were significantly increased by the treatment of HCQ. Salbutamol significantly elevated PKA and PKA activity levels and this was associated with the inhibition of the vacuolation and cell death. The PKA inhibitor significantly decreased the PKA levels and eliminated the protective effects of salbutamol on HCQ-treated RPE cells. CONCLUSION: The PKA pathway plays an important role in the protective effects of β2-adrenergic agonist on the RPE cells against HCQ toxicity. These findings reveal a novel potential strategy against HCQ retinopathy by treatment with PKA activating medications.
Ruihua Zhang, Dan-Ning Hu, Richard Rosen. ,/et al.Beta-adrenergic agonist protects retinal pigment epithelium against hydroxycholoroquine toxicity via cAMP-PKA signal pathway. Int J Ophthalmol, 2020,13(4):552-559
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