Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss.
OBJECTIVE
Previous analyses of the DBA/2J mouse glaucoma model show a sectorial degeneration pattern suggestive of an optic nerve head insult. In addition, there are large numbers of retinal ganglion cells (RGCs) that cannot be retrogradely labeled but maintain RGC gene expression, and many of these have somatic phosphorylated neurofilament labeling. Here the authors further elucidate these features of glaucomatous degeneration in a rat ocular hypertension model.


METHODS
IOP was elevated in Wistar rats by translimbal laser photocoagulation. Retina whole mounts were analyzed for Sncg mRNA in situ hybridization, fluorogold (FG) retrograde labeling, and immunohistochemistry for phosphorylated neurofilaments (pNF) at 10 and 29 days after IOP increase. A novel automatic method was used to estimate axon numbers in plastic sections of optic nerves.


RESULTS
Sncg mRNA was confirmed as a specific marker for RGCs in rat. Loss of RGCs after IOP elevation occurred in sectorial patterns. Sectors amid degeneration contained RGCs that were likely disconnected because these had pNF in their somas and dendrites, were not labeled by FG, and were associated with reactive plasticity within the retina. Most of the axon loss within the optic nerve already occurred by 10 days after the onset of IOP elevation.


CONCLUSIONS
These data demonstrate that the pattern of RGC loss after laser-induced ocular hypertension in rats is similar to that previously reported in DBA/2J mice. The results support the view that in glaucoma RGC axons are damaged at the optic nerve head and degenerate within the optic nerve before there is loss of RGC somas.
Soto
Ileana
I
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Pease
Mary E
ME
Son
Janice L
JL
Shi
Xiaohai
X
Quigley
Harry A
HA
Marsh-Armstrong
Nicholas
N
D000818:Animals; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D017403:In Situ Hybridization; D007429:Intraocular Pressure; D017075:Laser Coagulation; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D051845:gamma-Synuclein / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D051845:gamma-Synuclein
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