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Abstract #48121 Published in IGR 13-4
eNOS, a Pressure-Dependent Regulator of Intraocular Pressure
Stamer W; Lei Y; Boussommier-Calleja A; Overby D; Ethier CInvestigative Ophthalmology and Visual Science 2011; 52: 9438-9444
See also comment(s) by Paul Kaufman •
PURPOSE: Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure-dependent drainage of aqueous humor and thus intraocular pressure (IOP) are unknown. To better understand one possible underlying molecular factor regulating IOP, nitric oxide (NO), we studied pressure-dependent drainage in transgenic mice overexpressing endothelial NO synthase (eNOS). METHODS: IOP was measured by rebound tonometry (TonoLab) and pressure versus flow data was measured by ex vivo perfusion at multiple pressures between 8 and 45 mmHg, using mock AH ±100 MM L-NAME. A subset of eyes was examined histologically using standard techniques or assayed for fusion protein expression by Western blotting. RESULTS: IOP was lower (9.6 ± 2.7 versus 11.4 ± 2.5 mmHg; mean ± SD; p = 0.04) and pressure-dependent drainage was higher (0.0154 ± 0.006 versus 0.0066 ± 0.0009 μl/min/mmHg, p=0.002) in transgenic mice compared to wild-type animals; however, pressure-independent drainage was unaffected. The NOS inhibitor, L-NAME, normalized pressure-dependent drainage in transgenic animals. For IOP >35mmHg, the slope of the pressure-flow curve in wild-type mice increased to match that seen in transgenic mice. Shear stress in the pressure-dependent pathway at elevated pressures was calculated to be in a range known to affect eNOS expression/activity in vascular endothelia. CONCLUSIONS: Endothelial NOS overexpression lowers IOP by increasing pressure-dependent drainage in the mouse eye. Data are consistent with nitric oxide having a mechanoregulatory role in aqueous humor dynamics, with eNOS induction at elevated IOPs leading to increased pressure-dependent outflow.
Department of Ophthalmology and Vision Science, Department of Pharmacology, Department of Physiology, The University of Arizona, Tucson, AZ, USA.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)