Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix.
OBJECTIVE
To investigate the effect of IOP on retinal ganglion cell (RGC) apoptosis and correlate the effects with IOP-induced changes in extracellular matrix (ECM) in the retina and optic nerve head (ONH) in glaucomatous rat eyes.


METHODS
Thirty-seven Dark Agouti rats had elevated IOP induced in the left eye by hypertonic saline episcleral vein injections. Eyes were examined at 3 months histologically for RGC apoptosis and expression of specific ECM components.


RESULTS
RGC apoptosis was significantly related to IOP exposure (integral DeltaIOP P <0.001; peak IOP P <0.01). In the RGC layer, elevated IOP correlated positively to a significant increase in MMP-9 activity (P <0.001), tissue inhibitor of matrix metalloproteinase (TIMP-1) (P <0.05), and collagen I (P <0.01), and negatively correlated to deposition of laminin (P <0.05) and TGF-beta2 (P <0.05). There was a significant correlation between MMP-9 activity and both RGC apoptosis (P <0.001) and loss of laminin (P <0.01). IOP exposure was also associated with increased deposition of TGF-beta2 and collagen I at the ONH (P <0.01).


CONCLUSIONS
The results demonstrated that RGC apoptosis in glaucoma correlates strongly with elevated IOP and is significantly associated with IOP-induced changes in specific ECM components in the RGC layer. The study shows for the first time a link between MMP-9, laminin degradation, RGC apoptosis, and IOP exposure in glaucoma. The findings suggest that abnormal ECM remodeling in the glaucomatous retina may relate to RGC death and support the notion that the retina is a primary site of injury in glaucoma.
Guo
Li
L
Glaucoma and Optic Nerve Head Research Group, Department of Pathology, London, UK.
Moss
Stephen E
SE
Alexander
Robert A
RA
Ali
Robin R
RR
Fitzke
Frederick W
FW
Cordeiro
M Francesca
MF
D000818:Animals; D017209:Apoptosis; D024042:Collagen Type I / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology*; D007429:Intraocular Pressure; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009898:Optic Disk / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053781:Transforming Growth Factor beta2
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D020780:Matrix Metalloproteinase 9