Curcumin attenuates hydroxychloroquine-mediated apoptosis and oxidative stress via the inhibition of TRPM2 channel signalling pathways in a retinal pigment epithelium cell line.

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.

Effect of adalimumab on experimental corneal neovascularization model.

PURPOSE: To evaluate the efficacy of adalimumab (ADA) on inhibition of experimental corneal neovascularization (CNV) and compare the outcomes with bevacizumab (BEVA). METHODS: Twenty-four female Winstar rats (48 eyes) were used. Silver/Potassium Nitrate sticks were used for creating CNV. Forty-eight eyes of the rats were separated into 6 groups. The eyes which only NaCl was injected subconjunctivally (SC) formed Group-1. The eyes which CNV was created and NaCl, BEVA (2.5 mg/0.05 mL), ADA (2.5 mg/0.05 mL), respectively, were injected SC formed group-2, 3 and 4. The eyes which only BEVA and ADA, respectively, were injected SC formed group-5 and 6. Five days later the animals were sacrificed. Hematoxylin and eosin staining, Masson trichrome staining, Vascular endothelial growth factor (VEGF), and Platelet-derived growth factor (PDGF) antibodies were performed. RESULTS: Histochemical results showed that there was no histopathological finding in group-1, 5, and 6. Collagen fiber irregularity was observed in group-2 and there was a significant improvement in collagen fiber irregularity in group-3 and 4. Collagen fiber proliferation was higher in group-2 than in group-3 and 4. VEGF and PDGF stainings were not observed in group-1, 5, and 6. VEGF and PDGF stainings were observed in group-2 and significantly decreased in group-3 and 4 compared to group-2. ADA was found to be superior to BEVA in terms of decreasing VEGF staining. CONCLUSION: Both BEVA and ADA were effective in inhibiting CNV. Subconjunctival ADA seems to be more effective than BEVA in terms of inhibiting VEGF expression. Further experimental studies about ADA and BEVA are needed.