| First Author | Lei Y | Year | 2015 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 56 |
| Issue | 8 | Pages | 4891-8 |
| PubMed ID | 26225628 | Mgi Jnum | J:230950 |
| Mgi Id | MGI:5766581 | Doi | 10.1167/iovs.15-16564 |
| Citation | Lei Y, et al. (2015) Aqueous Humor Outflow Physiology in NOS3 Knockout Mice. Invest Ophthalmol Vis Sci 56(8):4891-8 |
| abstractText | PURPOSE: To investigate the role of endothelial nitric oxide synthase (eNOS) on conventional outflow function using NOS3 knockout (KO) mice. METHODS: Intraocular pressure was measured in both NOS3 KO and wild type (WT) by rebound tonometry. Outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. A subset of eyes was sectioned and stained for histology. Mock aqueous humor +/- the nitric oxide (NO) donors nitroprusside dihydrate (SNP) or S-Nitroso-N-Acetyl-D,L-Penicillamine (SNAP) was perfused into enucleated eyes. SNP and SNAP was administered topically at 0, 1, 2, and 3 hours while the contralateral eyes served as vehicle controls. Intraocular pressure was measured in both eyes before and after the last drug treatment. RESULTS: Intraocular pressure was higher in KO mice (18.2 +/- 0.7 mm Hg vs. 13.9 +/- 0.5 mm Hg, mean +/- SEM, n = 30, P < 0.05), and pressure-dependent conventional drainage was significantly lower (0.0058 +/- 0.0005 muL/min/mm Hg, mean +/- SEM, n = 21) compared with WT mice (0.0082 +/- 0.0013 muL/min/mm Hg, n = 23, P < 0.05). No obvious morphological differences in iridiocorneal angle tissues were observed in hematoxylin and eosin (H&E)-stained sections. SNP and SNAP significantly increased pressure-dependent drainage in KO animals (n = 12, P < 0.05). In WT mice, SNP and SNAP caused a significant increase in pressure dependent drainage (n = 12, P < 0.05) to a similar degree as in KO mice. Topical application of SNP significantly reduced IOP in WT and KO mice (n = 12, P < 0.05), but SNAP did not change IOP significantly (n = 19). CONCLUSIONS: NOS3 KO mice have elevated IOP, which is likely the result of reduced pressure-dependent drainage. These findings are consistent with human data showing polymorphisms in the NOS3 gene associate with ocular hypertension and the development of glaucoma. |
