Infliximab reduces Zaprinast-induced retinal degeneration in cultures of porcine retina

摘要: cGMP-degrading phosphodiesterase 6 (PDE6) mutations cause around 4 to 5% of retinitis pigmentosa (RP), a rare form retinal dystrophy. Growing evidence suggests that inflammation is involved in the progression RP. The aims this study were corroborate presence high TNFΑ concentration eyes RP patients and evaluate whether blockade with Infliximab, monoclonal anti-TNFΑ antibody, prevented degeneration induced by PDE6 inhibition cultures porcine retina. Aqueous humor from 30 13 healthy controls used quantify inflammatory mediators IL-6, TNFΑ, IL-1Β, IL-10 multiplex enzyme-linked immunosorbent assay (ELISA) system. Retinal explants pig exposed Zaprinast, inhibitor, for 24 hours absence or Infliximab. Cell death was evaluated TUNEL assay. number distribution caspase-3 positive cells, indirect poly(ADP)ribose polymerase (PARP) activation glial fibrillary acidic protein (GFAP) content visualized immunolabeling. Antioxidant total capacity, nitrites thiobarbituric acid reactive substances (TBARS) formation determined antioxidant-oxidant status. IL-6 concentrations higher aqueous than controls. Infliximab degeneration, as judging reduced TUNEL-positive reduction also activation, an ex vivo model Additionally, partially oxidative stress Zaprinast. Inflammatory elevated corroborating previous studies suggesting sustained chronic inflammation. Our playing important role cell activating different pathways at layers retina should be further studied.