Retinal Ganglion Cell Apoptosis Correlates With MMP–9 Activity and Laminin Degradation and is Related to the Level of IOP Exposure in a Rat Model of Glaucoma

Abstract

Abstract: : Purpose: Retinal ganglion cell (RGC) death has recently been linked to MMP–9 activity following optic nerve ligation. We have investigated retinal changes in MMP–9 and other extracellular matrix (ECM) components in relation to elevated IOP in a rat model of glaucoma. Methods: We assessed a rat model of chronic ocular hypertension (OHT, n=37), in which elevated IOP was induced using hypertonic saline episcleral vein injections, according to Morrison’s method. 12 animals underwent superior collicular application of DiAsp 10 days prior to the start of the study, to retrogradely label RGCs. Eyes were examined at 3 months histologically for RGC apoptosis and expression of MMP–9, laminin and other specific ECM components. Results: We found RGC apoptosis was significantly related to MMP–9 activity (p<0.001). Furthermore, elevated IOP was positively correlated to a significant increase in MMP–9 activity (p<0.001). There was a strong correlation between MMP–9 activity and laminin degradation (p<0.01). In the RGC layer, elevated IOP was positively correlated to a significant increase in TIMP–1 (p<0.05) and collagen I (p<0.01), and negatively correlated to deposition of laminin (p<0.05) and TGF–ß2 (p<0.05). Conclusions: We have demonstrated that RGC apoptosis in glaucoma is strongly linked with MMP–9 activity. This is correlated with IOP exposure, and laminin degradation in the RGC layer. Our study shows for the first time a link between MMP–9, laminin degradation, RGC apoptosis and IOP exposure in glaucoma. Our findings suggest that abnormal ECM remodelling in glaucomatous retina may relate to RGC death, and may support the possibility that the retina is a primary site of injury in glaucoma.

Keywords: apoptosis/cell death • intraocular pressure • extracellular matrix