Synaptic degeneration of retinal ganglion cells in a rat ocular hypertension glaucoma model.
OBJECTIVE
Glaucoma is a common neurodegenerative disease that affects retinal ganglion cells (RGCs) and their axons. Little is known of the synaptic degeneration involved in the pathophysiology of glaucoma. Here we used an experimental ocular hypertension model in rats to investigate this issue.


METHODS
Elevated intraocular pressure (IOP) was induced by laser coagulation of the episcleral and limbal veins. RGCs were retrogradely labeled with Fluoro-Gold (FG). The c-fos protein was used as a neuronal connectivity marker. Expression of c-fos in the retinas was investigated by immunohistochemistry at 5 days and 2 weeks after the induction of ocular hypertension. Both surviving RGCs as revealed by retrograde FG-labeled and c-fos-labeled RGCs were counted.


RESULTS
The c-fos protein was mainly expressed in the nuclei and nucleoli of cells in the ganglion cell layer and inner nuclear layer in the normal retina. We also confirmed that c-fos was also expressed in the nuclei and nucleoli of RGCs retrogradely labeled with FG. There was no significant RGC loss at 5 days but about 13% RGC loss at 2 weeks after the induction of ocular hypertension. The number of RGCs expressing c-fos was significantly lower in the experimental animals at both 5 days and 2 weeks than normal.


CONCLUSIONS
Our study suggests that there is synaptic disconnection for RGCs after ocular hypertension and it may precede the cell death in the early stage. It may provide insight into novel therapeutic strategies to slow the progress of glaucoma.
Fu
Qing-Ling
QL
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Li
Xin
X
Shi
Jianbo
J
Xu
Geng
G
Wen
Weiping
W
Lee
Daniel H S
DH
So
Kwok-Fai
KF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology*; D007429:Intraocular Pressure; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
D016760:Proto-Oncogene Proteins c-fos; D020169:Caspases