BACKGROUND The phytochemical ingredients of berries have been used in the treatment of various bodily ailments; while their roles in preventing the severity of glaucoma are poorly understood. Hence, the present study was framed to investigate whether ethanolic extracts of Lycium barbarum exerts protection against the onset of glaucoma using cultured PC12 neuronal cells by modulating the expression of extracellular matrix proteins. MATERIAL AND METHODS In order to develop glaucoma like condition in cells, cultured PC12 cells were subjected to 50 and 100 mmHg hydrostatic pressure for 24 hours. The pressure exposed cells were analyzed for the expression of glaucoma markers such as ANGPTL7 and the expressions of extracellular matrix proteins in the presence and absence of L. barbarum, matrix metalloproteinase (MMP)-9 inhibitor, and latanoprost, a current drug for the treatment of glaucoma. RESULTS PC12 cells exposed to hydrostatic pressures (50 and 100 mmHg) increased the expression of glaucoma marker, ANGPTL7. Moreover, results have demonstrated the significant changes in the expression of MMP-2, MMP-9, collagen I, and TGF-ß at the gene level. In contrast, cells pretreated with L. barbarum extracts showed reduced expression of ANGPTL7 and extracellular matrix proteins compared to control. Furthermore, to elucidate the role of MMP-9 in the onset of glaucoma, cells were silenced using MMP-9 inhibitor along with L. barbarum demonstrated a significant reduction in the glaucoma marker ANGPTL7 while improving the expression of caveolin-1 expression in cells subjected to pressure. CONCLUSIONS The extract of L. barbarum protects the cells from intraocular pressure by activating caveolin-1 dependent pathway via inhibition of MMP-9 expression.