ABSTRACT
PURPOSE: Hydroxychloroquine (HCQ) is used in the treatment of several diseases, such as malaria, Sjögren's disease, Covid-19, and rheumatoid arthritis. However, HCQ induces retinal pigment epithelium death via the excessive increase of cytosolic (cROS) and mitochondrial (mROS) free oxygen radical production. The transient receptor potential melastatin 2 (TRPM2) cation channel is stimulated by ADP-ribose (ADPR), cROS, and mROS, although it is inhibited by curcumin (CRC). We aimed to investigate the modulating action of CRC on HCQ-induced TRPM2 stimulation, cROS, mROS, apoptosis, and death in an adult retinal pigment epithelial 19 (ARPE19) cell line model. MATERIAL AND METHODS: ARPE19 cells were divided into four groups: control (CNT), CRC (5 µM for 24 h), HCQ (60 µM for 48 h), and CRC + HCQ groups. RESULTS: The levels of cell death (propidium iodide positive cell numbers), apoptosis markers (caspases -3, -8, and -9), oxidative stress (cROS and mROS), mitochondria membrane depolarization, TRPM2 current density, and intracellular free Ca2+ and Zn2+ fluorescence intensity were upregulated in the HCQ group after stimulation with hydrogen peroxide and ADPR, but their levels were downregulated by treatments with CRC and TRPM2 blockers (ACA and carvacrol). The HCQ-induced decrease in retinal live cell count and cell viability was counteracted by treatment with CRC. CONCLUSION: HCQ-mediated overload Ca2+ influx and retinal oxidative toxicity were induced in an ARPE19 cell line through the stimulation of TRPM2, although they were attenuated by treatment with CRC. Hence, CRC may be a potential therapeutic antioxidant for TRPM2 activation and HCQ treatment-induced retinal oxidative injury and apoptosis.
ABSTRACT
Irreversible visual loss due to retinal toxicity is one of the side effects of hydroxychloroquine (HCQ) therapy. The recent outbreak of the novel coronavirus-19 (COVID 19) has seen HCQ proposed as a possible treatment and prophylactic drug, leading to its increased use. Many are unaware of its ocular side effects. We describe a case of HCQ-induced retinopathy in a 46-year-old female who was referred by a rheumatologist for routine eye review.
Résumé La perte de vision irréversible secondaire à la toxicité rétinienne est l'un des effets indésirables du traitement à l'hydroxychloroquine (HCQ). Nous décrivons un cas d'une patiente âgée de 46 ans, présentant une rétinopathie secondaire au traitement à l'HCQ référée par un Rhumathologue pour un examen ophtalmique. Mots-clés: Hydroxychloroquine, rétine toxicité rétinienne, rétinopathie.