Effect of αvβ3 Integrin Expression and Activity on Intraocular Pressure

PURPOSE: To determine the effects of αvβ3 integrin expression and activation on intraocular pressure (IOP). METHODS: Cre(+/−)β3(flox/flox) mice were treated with topical tamoxifen eye drops for 5 days to activate Cre and excise the β3 integrin gene from the anterior segment. IOP was measured weekly for 11 weeks using rebound tonometry. Mice were then killed and changes in expression of the β3 integrin subunit in Cre(+/−) β3(flox/flox) mice were determined using Western blotting analysis and immunofluorescence microscopy. To determine the effect of αvβ3 integrin activation on outflow facility, porcine organ culture anterior segments (POCAS) were perfused with the αvβ3 integrin-activating antibody AP5 or an isotype IgG control for 21 hours. The effect of αvβ3 integrin activation on IOP was measured over 7 days in C57BL/6J mice intracamerally infused with AP5, AP3, IgG, or PBS. RESULTS: Deletion of the β3 integrin subunit using the tamoxifen-inducible Cre-loxP system resulted in a decrease in expression of the β3 integrin subunit in the trabecular meshwork and ciliary muscle. Morphologically no gross changes in the anterior segment were detected. Deletion of the β3 integrin subunit resulted in a significantly (P < 0.05) lower IOP in mice within 2 weeks following the tamoxifen treatment and persisted for 11 weeks. Activating the αvβ3 integrin with the AP5 antibody resulted in a significant (P < 0.05) increase in IOP in C57BL/6J mice and a decrease in outflow facility in 42% of the POCAS. CONCLUSIONS: These studies demonstrate a role for αvβ3 integrin signaling in the regulation of IOP.