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Yuan Lei, Maomao Song, Jihong Wu, Chao Xing, Xinghuai Sun; eNOS Activity in CAV1 Knockout Mouse Eyes. Invest. Ophthalmol. Vis. Sci. 2016;57(6):2805-2813. doi: https://doi.org/10.1167/iovs.15-18841.
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To investigate endothelial nitric oxide synthase (eNOS) activity and the response of conventional outflow facility to nitric oxide donors and a nitric oxide synthase (NOS) inhibitor in caveolin-1 (CAV1) knockout (KO) mice.
Intraocular pressure (IOP) was measured in both CAV1 KO and wild-type (WT) mice by rebound tonometry. The expressions of caveolin-2 (CAV2), eNOS, eNOS-phospho Ser1177, eNOS-phospho Thr495, Akt, Akt-phospho Ser473, and nitrotyrosin were measured by Western blot analysis. Nitric oxide donor sodium nitroprusside (SNP), S-nitroso-N-acetyl-D,L-penicillamine (SNAP), or the NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) were administered topically. The outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps.
CAV1 KO mice have elevated IOP and reduced conventional outflow facility when compared with WT mice. CAV2 expression was absent in CAV1 KO mice, but we observed increased expressions of eNOS, eNOS-phospho Ser1177, Akt, Akt-phospho Ser473, and nitrotyrosin and reduced expression of eNOS-phospho Thr495. Topical application of SNP significantly reduced IOP in WT and KO mice by 1.6 fold (n = 6, P < 0.05), but SNAP did not change IOP significantly (n = 6, P > 0.05). In comparison, the NOS inhibitor L-NAME significantly increased IOP by 50% in KO mice (n = 6, P < 0.05). SNP and SNAP significantly increased, whereas L-NAME significantly reduced pressure-dependent drainage in KO animals.
Although CAV1 KO mice had elevated IOP and decreased outflow facility, CAV1 deficiency (and possibly the loss of CAV2) resulted in increased eNOS activity. The pressure elevation may be a result of increased tyrosine nitration of protein kinase K and impairment of its activity in KO mice.
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