We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Novel role for the δ-opioid receptor in hypoxic preconditioning in rat retinas.
- Authors
Pai-Huei Peng; Ho-Shiang Huang; Yih-Jing Lee; Yih-Sharng Chen; Ming-Chieh Ma
- 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.
- Subjects
OPIOID receptors; HYPOXEMIA; INTRAOCULAR pressure; OXIDATIVE stress; RETINA; LABORATORY mice
- Publication
Journal of Neurochemistry, 2009, Vol 108, Issue 3, p741
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2008.05807.x