{"65561":{"#nid":"65561","#data":{"type":"event","title":"Nitric Oxide and Mechanoregulation of Intraocular Pressure","body":[{"value":"\u003Cp\u003E\u003Cem\u003EAbstract\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003EGlaucoma is the second most common cause of blindness, and in most cases is due to higher-than-normal intraocular pressure (IOP). Our understanding of the factors controlling IOP is very incomplete, hindering the development of next generation drugs for IOP control. In this study, we sought to better understand molecular factors controlling aqueous humour (AH) drainage, responsible for determining IOP. To do so, we first estimated and then indirectly inferred wall shear stress magnitudes acting on the endothelial cells of Schlemm\u2019s canal, the main AH drainage site from the eye. We then measured intraocular pressure (IOP) and AH dynamics in wild-type and transgenic C57BL\/6 mice overexpressing a fusion protein of active endothelial nitric oxide synthase (eNOS) and GFP (Haperin et al., Am J Pathology, 2003). IOP was measured by rebound tonometry (TonoLab) and pressure vs. flow data was measured by ex vivo ocular perfusion at multiple perfusion pressures between 4 and 35 mmHg, using either mock AH or mock AH plus the NOS inhibitor 100 mM L-NAME. A subset of eyes was examined histologically using standard techniques or labelled to identify the distribution of eNOS, while eNOS expression was assayed in other eyes by Western blotting. In transgenic mice, IOP was lower (9.6 \u00b1 0.6 vs 11.5 \u00b1 0.5 mmHg; mean \u00b1 SD; p = 0.026) and conventional (pressure-dependent) AH drainage resistance was 19% lower, as compared to wild-type controls. Increased AH drainage in transgenic animals was abolished by the NOS inhibitor L-NAME. Western blots showed higher levels of eNOS expression in ocular tissues, while histology showed increased eNOS\/GFP fusion protein expression in the trabecular meshwork and inner wall of Schlemm\u2019s canal without structural changes in outflow tissue architecture. Theoretical calculations showed that the expected shear stress due to AH flow in Schlemm\u0027s canal of the mouse was comparable to that in human and in a range known to affect eNOS expression. We conclude that eNOS overexpression lowers IOP by increasing conventional (trabecular) aqueous drainage in the mouse eye. Our data are consistent with NO having a regulatory role in IOP control, specifically with eNOS induction at high IOPs\/AH drainage rates. This represents an interesting pharmacologic target (see e.g. Borghi et al, J Ocul Pharmacol Ther. 2010), especially in light of recent reports of polymorphisms in the NOS3 gene associating with ocular hypertension in glaucoma. The seminar will conclude with discussion of a possible mechanoregulatory pathway for IOP control, acting through NO.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBME Special Seminar\u003C\/p\u003E\u003Cp\u003E\u0022Nitric Oxide and Mechanoregulation of Intraocular Pressure\u0022\u003C\/p\u003E\u003Cp\u003ERoss Ethier, PhD - Imperial College of London\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Ross Ethier, PhD - Imperial College of London"}],"uid":"27195","created_gmt":"2011-04-14 08:59:19","changed_gmt":"2016-10-08 01:54:46","author":"Colly Mitchell","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2011-04-28T12:00:00-04:00","event_time_end":"2011-04-28T13:00:00-04:00","event_time_end_last":"2011-04-28T13:00:00-04:00","gmt_time_start":"2011-04-28 16:00:00","gmt_time_end":"2011-04-28 17:00:00","gmt_time_end_last":"2011-04-28 17:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"hg_media":{"65563":{"id":"65563","type":"image","title":"Ross Ethier, PhD - Imperial College of London","body":null,"created":"1449176863","gmt_created":"2015-12-03 21:07:43","changed":"1475894579","gmt_changed":"2016-10-08 02:42:59","alt":"Ross Ethier, PhD - Imperial College of London","file":{"fid":"192275","name":"Ross_portrait_2009_small.jpg","image_path":"\/sites\/default\/files\/images\/Ross_portrait_2009_small_0.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/Ross_portrait_2009_small_0.jpg","mime":"image\/jpeg","size":3085469,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Ross_portrait_2009_small_0.jpg?itok=dVFwySLx"}}},"media_ids":["65563"],"related_links":[{"url":"http:\/\/www3.imperial.ac.uk\/people\/r.ethier","title":"Ethier lab"}],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"248","name":"IBB"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EGail Spatt\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}