Novel role for the δ-opioid receptor in hypoxic preconditioning in rat retinas |
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Authors: | Pai-Huei Peng Ho-Shiang Huang† Yih-Jing Lee‡ Yih-Sharng Chen§ Ming-Chieh Ma‡ |
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Institution: | Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Department of Urology, National Taiwan University Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, Hsinchuang, Taiwan; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan |
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Abstract: | δ-Opioid receptor (DOR) is an oxygen-sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)-mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro-apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8-iso-prostaglandin F2α accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia-inducible factor-1α (HIF-1α) and DOR, but intravitreal administration of HIF-1α-specific small interfering RNA abrogated the up-regulation of DOR. This suggested that DOR functions downstream of HIF-1α. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC-induced protection and activation of extracellular signal-regulated kinase. These results suggest a novel mechanism of HPC-mediated retinoprotection whereby HIF-1α induces the expression of DOR, and DOR-mediated activation of extracellular signal-regulated kinase triggers cellular events that correct the redox imbalance in the post-ischemic retina. |
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Keywords: | δ-opioid receptor extracellular signal-regulated kinase hypoxia-inducible factor-1α hypoxic preconditioning intraocular pressure oxidative stress |
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