First Author | Faralli JA | Year | 2019 |
Journal | Invest Ophthalmol Vis Sci | Volume | 60 |
Issue | 5 | Pages | 1776-1788 |
PubMed ID | 31022732 | Mgi Jnum | J:274810 |
Mgi Id | MGI:6295880 | Doi | 10.1167/iovs.18-26038 |
Citation | Faralli JA, et al. (2019) Effect of alphavbeta3 Integrin Expression and Activity on Intraocular Pressure. Invest Ophthalmol Vis Sci 60(5):1776-1788 |
abstractText | Purpose: To determine the effects of alphavbeta3 integrin expression and activation on intraocular pressure (IOP). Methods: Cre+/-beta3flox/flox mice were treated with topical tamoxifen eye drops for 5 days to activate Cre and excise the beta3 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 beta3 integrin subunit in Cre+/- beta3flox/flox mice were determined using Western blotting analysis and immunofluorescence microscopy. To determine the effect of alphavbeta3 integrin activation on outflow facility, porcine organ culture anterior segments (POCAS) were perfused with the alphavbeta3 integrin-activating antibody AP5 or an isotype IgG control for 21 hours. The effect of alphavbeta3 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 beta3 integrin subunit using the tamoxifen-inducible Cre-loxP system resulted in a decrease in expression of the beta3 integrin subunit in the trabecular meshwork and ciliary muscle. Morphologically no gross changes in the anterior segment were detected. Deletion of the beta3 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 alphavbeta3 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 alphavbeta3 integrin signaling in the regulation of IOP. |