Evaluation of inducible nitric oxide synthase in glaucomatous optic neuropathy and pressure-induced optic nerve damage.
OBJECTIVE
To determine whether inducible nitric oxide synthase (NOS-2) is involved in glaucomatous optic neuropathy.


METHODS
Chronic elevation of rat intraocular pressure (IOP) leading to optic nerve damage was induced by episcleral injection of hypertonic saline, which caused sclerosis and blockade of aqueous humor outflow pathways. Expression of NOS-2 in the retina and optic nerve head (ONH) was evaluated by immunohistochemistry, gene array analysis, and quantitative PCR (Q-PCR). Immunohistochemistry was also used to assess the NOS-2 level in the ONH from primary open-angle glaucoma (POAG) and nonglaucomatous human eyes. Finally, an NOS-2 inhibitor, aminoguanidine, administered orally in the drinking water, was tested for its effect on optic nerve injury in rats with ocular hypertension.


RESULTS
Chronically elevated IOP in the rat produced optic nerve damage that correlated with pressure change (r(2) = 0.77), but did not increase NOS-2 immunoreactivity in the optic nerve, ONH, or ganglion cell layer. Retinal and ONH NOS-2 mRNA levels did not correlate with either IOP level or severity of optic nerve injury. Similarly, there was no difference in NOS-2 immunoreactivity in the optic nerve or ONH between POAG and nonglaucomatous eyes. Furthermore, aminoguanidine treatment did not affect the development of pressure-induced optic neuropathy in the rat.


CONCLUSIONS
As demonstrated by several independent methods, glaucomatous optic neuropathy was not associated with a significant change in the expression of NOS-2 in the retina, ONH, or optic nerve.
Pang
Iok-Hou
IH
Alcon Research, Ltd., Fort Worth, Texas, USA. iok-hou.pang@alconlabs.com
Johnson
Elaine C
EC
Jia
Lijun
L
Cepurna
William O
WO
Shepard
Allan R
AR
Hellberg
Mark R
MR
Clark
Abbot F
AF
Morrison
John C
JC
D000368:Aged; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D005902:Glaucoma, Open-Angle / Q000201:enzymology*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007429:Intraocular Pressure; D008297:Male; D009798:Ocular Hypertension / Q000201:enzymology; D009898:Optic Disk / Q000201:enzymology*; D009901:Optic Nerve Diseases / Q000201:enzymology*; D020221:Optic Nerve Injuries / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000201:enzymology*
D029742:Caenorhabditis elegans Proteins; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; C400703:nos-2 protein, C elegans; C004479:pimagedine