This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (24)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Ophthalmology, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

James Morgan, DPhil, FRCOphth; Joseph Caprioli, MD; Yoshiyuki Koseki, MD

Arch Ophthalmol. 1999;117:1524-1529.

Background  Nitric oxide has been implicated in the process of retinal ganglion cell death in glaucoma.

Objective  To investigate the role of nitric oxide in mediating retinal ganglion cell death in a culture system that models glial-neuronal interactions at the level of the optic nerve head.

Methods  Dissociated retinal ganglion cells from neonatal rats were plated on monolayers of astroglia and identified by retrograde labeling with the fluorescent marker 1.1-dioctadecyl-,3,3,3,tetramethylindocarbocyanineperchlorate. Two days after dissociation, cocultures of retinal ganglion cells and glia were treated with graded concentrations of the nitric oxide synthase inhibitor N-nitro-L-arginine (NNA), and exposed to either anoxia for 1 to 24 hours or excitatory amino acids for 6 hours. Surviving retinal ganglion cells were counted with fluorescence microscopy and expressed as a percentage of retinal ganglion cells surviving in control cultures.

Results  Cell survival after anoxia increased in a dose-dependent fashion with exposure to NNA. Mean±SD survival rate of retinal ganglion cells after 6 hours of anoxia was 57%±10% with NNA treatment compared with 31%±3% without treatment (P<.01). When treated with excitatory amino acids, cell survival was 31%±6% after administration of N-methyl D-aspartate, 500 µmol/L, and 27%±8% after administration of sodium glutamate, 500 µmol/L. Survival was increased in cultures with exposure to NNA, 100 µmol/L, to 53%±11% and 69%±11%, respectively (P<.01).

Conclusion  In this coculture of retinal ganglion cells and astroglia, reduction of the glial source of nitric oxide through nitric oxide synthase inhibition provided partial but significant protection against the lethal effects of anoxia and excitatory amino acids on retinal ganglion cells.

Clinical Relevance  Neuroprotective agents may play a role in patients with glaucoma who have progressive visual field loss, despite satisfactory control of intraocular pressure. Inhibition of nitric oxide synthase at the level of the optic nerve head may contribute to a clinically significant level of neuroprotection.

From the Cardiff Eye Unit, University Hospital of Wales (Dr Morgan); Glaucoma Division, Jules Stein Eye Institute, University of California at Los Angeles School of Medicine (Dr Caprioli); and Department of Ophthalmology, Yale University School of Medicine, New Haven, Conn (Dr Koseki).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Activation of Matrix Metalloproteinase-9 via Neuronal Nitric Oxide Synthase Contributes to NMDA-Induced Retinal Ganglion Cell Death
Manabe et al.
IOVS 2005;46:4747-4753.
ABSTRACT | FULL TEXT  

Hypoxia-Inducible Factor 1{alpha} in the Glaucomatous Retina and Optic Nerve Head
Tezel and Wax
Arch Ophthalmol 2004;122:1348-1356.
ABSTRACT | FULL TEXT  

Gene Expression Profiling of Purified Rat Retinal Ganglion Cells
Farkas et al.
IOVS 2004;45:2503-2513.
ABSTRACT | FULL TEXT  

Early Glial Responses after Acute Elevated Intraocular Pressure in Rats
Lam et al.
IOVS 2003;44:638-645.
ABSTRACT | FULL TEXT  

Hypoglycemia Induces General Neuronal Death, Whereas Hypoxia and Glutamate Transport Blockade Lead to Selective Retinal Ganglion Cell Death In Vitro
Luo et al.
IOVS 2001;42:2695-2705.
ABSTRACT | FULL TEXT  

Neuroprotective Effect and Intraocular Penetration of Nipradilol, a {beta}-Blocker with Nitric Oxide Donative Action
Mizuno et al.
IOVS 2001;42:688-694.
ABSTRACT | FULL TEXT