TY - JOUR
T1 - Pharmacological consequences of oxidative stress in ocular tissues
AU - Ohia, Sunny E.
AU - Opere, Catherine A.
AU - Leday, Angela M.
N1 - Funding Information:
The authors thank Ms. Carolyn Wahl and Mary Reed for their excellent secretarial assistance. Some of the studies reported in this manuscript were supported by National Institutes of Health grants to Drs. Sunny E. Ohia (EY11023, EY12157 and EY13266) and Catherine A. Opere (EY13967).
PY - 2005/11/11
Y1 - 2005/11/11
N2 - The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H
2O
2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H
2O
2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [
3H] d-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H
2O
2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.
AB - The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H
2O
2 and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris-ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H
2O
2 and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [
3H] d-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H
2O
2 to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.
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U2 - 10.1016/j.mrfmmm.2005.03.025
DO - 10.1016/j.mrfmmm.2005.03.025
M3 - Review article
C2 - 16055157
AN - SCOPUS:27544459505
VL - 579
SP - 22
EP - 36
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
SN - 1386-1964
IS - 1-2
ER -