Oxidative injury by peroxynitrite in neural and vascular tissue of the lateral geniculate nucleus in experimental glaucoma.
In glaucoma, recent studies show that neural degeneration extends beyond the retinal ganglion cells to include target neurons in the lateral geniculate nucleus of the brain. The pathobiology of LGN degeneration in glaucoma is as yet unknown. We investigated whether peroxynitrite-mediated oxidative stress plays a role in glaucomatous degeneration of the LGN. Nitrotyrosine (NT), a marker for peroxynitrite-mediated oxidative injury, was studied in right LGN sections from monkeys with experimental unilateral glaucoma in the right eye and from normal controls. Immunoreactivity for NT was analyzed using bright-field microscopy. The density of NT profiles localized in neural tissue was determined for LGN layers (2,3,5) connected to the glaucoma eye and LGN layers (1,4,6) connected to the non-glaucoma eye. Density was calculated for each LGN layer by dividing the number of NT profiles by the cross-sectional area of each LGN layer. Blood vessels in each LGN were examined for NT formation. NT formation was detected in LGN layers of all monkeys with glaucoma. Quantitative analysis revealed that compared to controls, the density of NT profiles was increased in monkeys with glaucoma in LGN layers connected to glaucoma and non-glaucoma eyes. The mean density of NT profiles (+/-SEM) in neural tissue was significantly increased in glaucoma LGN layers compared to those of controls (2.30+/-0.56 vs. 0.29+/-0.12; P=0.016). Nitrotyrosine was readily apparent in LGN blood vessel endothelium in glaucoma, and not detected in blood vessels of control LGNs. The presence of NT in neural and vascular tissue of the glaucomatous LGN implicates peroxynitrite-mediated oxidative cell injury in the pathobiology of central neural degeneration in glaucoma.
Luthra
Anchla
A
Department of Ophthalmology and Vision Sciences, Faculty of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada.
Gupta
Neeru
N
Kaufman
Paul L
PL
Weinreb
Robert N
RN
Yücel
Yeni H
YH
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D005829:Geniculate Bodies / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D005901:Glaucoma / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine