Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model.
BACKGROUND
Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model.


METHODS
The expression of Nos2 in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration, a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice.


RESULTS
Optic nerve head Nos2 RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage.


CONCLUSIONS
Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of Nos2 in glaucoma.
Libby
Richard T
RT
The Jackson Laboratory, Bar Harbor, ME 04609, USA. Richard_Libby@URMC.rochester.edu
Howell
Gareth R
GR
Pang
Iok-Hou
IH
Savinova
Olga V
OV
Mehalow
Adrienne K
AK
Barter
Joseph W
JW
Smith
Richard S
RS
Clark
Abbot F
AF
John
Simon W M
SW
D000818:Animals; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D007429:Intraocular Pressure; D051379:Mice; D008811:Mice, Inbred DBA; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009898:Optic Disk / Q000201:enzymology* / Q000473:pathology; D009901:Optic Nerve Diseases / Q000201:enzymology* / Q000473:pathology; D012164:Retinal Diseases / Q000201:enzymology* / Q000473:pathology
D052247:Nitric Oxide Synthase Type II