Effects of transient ischemia by four vessel occlusion on the retina in rats treated with the selective neuronal NOS inhibitor 7-nitroindazole

Toya Kimble, S. Cuthbertson, M. E.C. Fitzgerald, G. Sancesario, Thaddeus Nowak, W. Pulsinelli, Anton Reiner

Research output: Contribution to journalArticle

Abstract

Purpose. Prior studies on ischemic damage to the retina produced by ligation of the central retinal artery have indicated that production of nitric oxide (NO) by ischemia-induced macrophage nitric oxide synthase (iNOS) plays a role in the ischemic injury. In the present study, we examined: 1) the ability of transient global ischemia produced by four vessel occlusion (4VO, vertebral and common carotid arteries) to produce ischemic retinal injury; and 2) the effect of a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), on the retinal injury produced by 4VO. Methods. Retinal ischemia was produced by 20 min 4VO. In one group of 20 min 4VO rats, 25 mg/kg 7NI was administered ip immediately and then again 3hr and 6hr after reperfusion, while another group of 20 min 4VO rats received vehicle alone at the same time points. Sham rats received vertebral artery occlusion without carotid clamping. General damage to retina was assessed histologically 3 days after ischemia. Specific retinal changes were assessed histochemically (NOS localization was visualized by NADPH-diaphorase histochemistry), or immunohistochemically (using GFAP as a marker of retinal injury, and such markers of retinal cells types as choline acetyltransferase (CHAT) and glutamic acid decarboxylase (GAD). Results. In sham retina, CHAT was observed in starburst amacrine cells and their IPL fibers and GAD was observed in amacrine cells and fibers in the IPL. Minimal GFAP labeling was observed in the retina, other than in the optic nerve fiber layer. In the 4VO+vehicle rats, although the retina appeared histologically normal, and retinal CHAT+ and GAD+ labeling was not obviously diminished, GFAP+ Müller cells were evident throughout the retina and NADPH-diaphorase+ labeling was increased in the optic nerve fiber layer. This pattern was unaltered by 7NI treatment. Concluions. These results indicate that transient 4VO produces retinal ischemia and the damage at the time point examined is not obviously affected by a selective nNOS inhibition. The latter finding is consistent with evidence that NO-mediated damage in global retinal ischemia is attributable to iNOS.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

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Retina
Ischemia
Glutamate Decarboxylase
Choline O-Acetyltransferase
Amacrine Cells
NADPH Dehydrogenase
Nitric Oxide Synthase Type I
Wounds and Injuries
Optic Nerve
Nerve Fibers
Nitric Oxide Synthase
Nitric Oxide
Macrophages
Retinal Artery
Vertebral Artery
Common Carotid Artery
Constriction
Reperfusion
Ligation
7-nitroindazole

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effects of transient ischemia by four vessel occlusion on the retina in rats treated with the selective neuronal NOS inhibitor 7-nitroindazole. / Kimble, Toya; Cuthbertson, S.; Fitzgerald, M. E.C.; Sancesario, G.; Nowak, Thaddeus; Pulsinelli, W.; Reiner, Anton.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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abstract = "Purpose. Prior studies on ischemic damage to the retina produced by ligation of the central retinal artery have indicated that production of nitric oxide (NO) by ischemia-induced macrophage nitric oxide synthase (iNOS) plays a role in the ischemic injury. In the present study, we examined: 1) the ability of transient global ischemia produced by four vessel occlusion (4VO, vertebral and common carotid arteries) to produce ischemic retinal injury; and 2) the effect of a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), on the retinal injury produced by 4VO. Methods. Retinal ischemia was produced by 20 min 4VO. In one group of 20 min 4VO rats, 25 mg/kg 7NI was administered ip immediately and then again 3hr and 6hr after reperfusion, while another group of 20 min 4VO rats received vehicle alone at the same time points. Sham rats received vertebral artery occlusion without carotid clamping. General damage to retina was assessed histologically 3 days after ischemia. Specific retinal changes were assessed histochemically (NOS localization was visualized by NADPH-diaphorase histochemistry), or immunohistochemically (using GFAP as a marker of retinal injury, and such markers of retinal cells types as choline acetyltransferase (CHAT) and glutamic acid decarboxylase (GAD). Results. In sham retina, CHAT was observed in starburst amacrine cells and their IPL fibers and GAD was observed in amacrine cells and fibers in the IPL. Minimal GFAP labeling was observed in the retina, other than in the optic nerve fiber layer. In the 4VO+vehicle rats, although the retina appeared histologically normal, and retinal CHAT+ and GAD+ labeling was not obviously diminished, GFAP+ M{\"u}ller cells were evident throughout the retina and NADPH-diaphorase+ labeling was increased in the optic nerve fiber layer. This pattern was unaltered by 7NI treatment. Concluions. These results indicate that transient 4VO produces retinal ischemia and the damage at the time point examined is not obviously affected by a selective nNOS inhibition. The latter finding is consistent with evidence that NO-mediated damage in global retinal ischemia is attributable to iNOS.",
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T1 - Effects of transient ischemia by four vessel occlusion on the retina in rats treated with the selective neuronal NOS inhibitor 7-nitroindazole

AU - Kimble, Toya

AU - Cuthbertson, S.

AU - Fitzgerald, M. E.C.

AU - Sancesario, G.

AU - Nowak, Thaddeus

AU - Pulsinelli, W.

AU - Reiner, Anton

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N2 - Purpose. Prior studies on ischemic damage to the retina produced by ligation of the central retinal artery have indicated that production of nitric oxide (NO) by ischemia-induced macrophage nitric oxide synthase (iNOS) plays a role in the ischemic injury. In the present study, we examined: 1) the ability of transient global ischemia produced by four vessel occlusion (4VO, vertebral and common carotid arteries) to produce ischemic retinal injury; and 2) the effect of a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), on the retinal injury produced by 4VO. Methods. Retinal ischemia was produced by 20 min 4VO. In one group of 20 min 4VO rats, 25 mg/kg 7NI was administered ip immediately and then again 3hr and 6hr after reperfusion, while another group of 20 min 4VO rats received vehicle alone at the same time points. Sham rats received vertebral artery occlusion without carotid clamping. General damage to retina was assessed histologically 3 days after ischemia. Specific retinal changes were assessed histochemically (NOS localization was visualized by NADPH-diaphorase histochemistry), or immunohistochemically (using GFAP as a marker of retinal injury, and such markers of retinal cells types as choline acetyltransferase (CHAT) and glutamic acid decarboxylase (GAD). Results. In sham retina, CHAT was observed in starburst amacrine cells and their IPL fibers and GAD was observed in amacrine cells and fibers in the IPL. Minimal GFAP labeling was observed in the retina, other than in the optic nerve fiber layer. In the 4VO+vehicle rats, although the retina appeared histologically normal, and retinal CHAT+ and GAD+ labeling was not obviously diminished, GFAP+ Müller cells were evident throughout the retina and NADPH-diaphorase+ labeling was increased in the optic nerve fiber layer. This pattern was unaltered by 7NI treatment. Concluions. These results indicate that transient 4VO produces retinal ischemia and the damage at the time point examined is not obviously affected by a selective nNOS inhibition. The latter finding is consistent with evidence that NO-mediated damage in global retinal ischemia is attributable to iNOS.

AB - Purpose. Prior studies on ischemic damage to the retina produced by ligation of the central retinal artery have indicated that production of nitric oxide (NO) by ischemia-induced macrophage nitric oxide synthase (iNOS) plays a role in the ischemic injury. In the present study, we examined: 1) the ability of transient global ischemia produced by four vessel occlusion (4VO, vertebral and common carotid arteries) to produce ischemic retinal injury; and 2) the effect of a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), on the retinal injury produced by 4VO. Methods. Retinal ischemia was produced by 20 min 4VO. In one group of 20 min 4VO rats, 25 mg/kg 7NI was administered ip immediately and then again 3hr and 6hr after reperfusion, while another group of 20 min 4VO rats received vehicle alone at the same time points. Sham rats received vertebral artery occlusion without carotid clamping. General damage to retina was assessed histologically 3 days after ischemia. Specific retinal changes were assessed histochemically (NOS localization was visualized by NADPH-diaphorase histochemistry), or immunohistochemically (using GFAP as a marker of retinal injury, and such markers of retinal cells types as choline acetyltransferase (CHAT) and glutamic acid decarboxylase (GAD). Results. In sham retina, CHAT was observed in starburst amacrine cells and their IPL fibers and GAD was observed in amacrine cells and fibers in the IPL. Minimal GFAP labeling was observed in the retina, other than in the optic nerve fiber layer. In the 4VO+vehicle rats, although the retina appeared histologically normal, and retinal CHAT+ and GAD+ labeling was not obviously diminished, GFAP+ Müller cells were evident throughout the retina and NADPH-diaphorase+ labeling was increased in the optic nerve fiber layer. This pattern was unaltered by 7NI treatment. Concluions. These results indicate that transient 4VO produces retinal ischemia and the damage at the time point examined is not obviously affected by a selective nNOS inhibition. The latter finding is consistent with evidence that NO-mediated damage in global retinal ischemia is attributable to iNOS.

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