The selective vulnerability of retinal ganglion cells in rat chronic ocular hypertension model at early phase.
Glutamate neurotoxicity has been postulated to play a prominent role in glaucoma. In this study the possible roles of two subunits of glutamate receptors during the early phase of retinal ganglion cell (RGC) loss in a rat chronic ocular hypertension (COH) model were investigated. COH was induced by applying argon laser to the episcleral and limbal veins of the right eye of rats, the observation times were at 4, 14 and 28 days after the first laser. RGCs were retrogradely labeled by putting Fluoro-Gold (FG) on the surface of both side superior colliculus. Immunohistochemical staining using specific antibodies against N-methyl-D-aspartate receptor 1 (NR1) or glutamate receptor 2/3 (GluR2/3) was performed on the retinal sections of normal and COH eyes. Fluorescent images were captured using confocal laser scanning microscope and the number of NR1 and GluR2/3 labeled cells were counted and cell size was measured using Stereo Investigator. During the observation period, the numbers of NR1 and GluR2/3 positive RGCs in the RGC layer were reduced parallel to the loss of RGC. The dramatic loss of GluR2/3 immunoreactive neurons occurred starting immediately after the first laser to 4 days while the dramatic loss of NR1 immunoreactive neurons occurred from 14 to 28 days after the first laser. Size difference was detected in NR1 immunoreactive RGCs, large ones were more sensitive to the high ocular pressure. These results suggest that both NR1 and GluR2/3 are involved in the mediation of RGC death in the early stage of COH.
Luo
Xue-Gang
XG
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, 21 Sassoon Road, Hong Kong, China.
Chiu
Kin
K
Lau
Flora H S
FH
Lee
Vincent W H
VW
Yung
Ken K L
KK
So
Kwok-Fai
KF
D000818:Animals; D048429:Cell Size; D002470:Cell Survival; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology; D007429:Intraocular Pressure / Q000502:physiology; D008028:Light Coagulation; D018613:Microscopy, Confocal; D009798:Ocular Hypertension / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2