@article {1109911, title = {A Compact Whole-Eye Perfusion System to Evaluate Pharmacologic Responses of Outflow Facility}, journal = {Invest Ophthalmol Vis Sci}, volume = {58}, number = {7}, year = {2017}, month = {2017 Jun 01}, pages = {2991-3003}, abstract = {Purpose: To discover novel therapies that lower IOP by increasing aqueous humor outflow facility, ex vivo ocular perfusion systems provide a valuable tool. However, currently available designs are limited by their throughput. Here we report the development of a compact, scalable perfusion system with improved throughput and its validation using bovine and porcine eyes. Methods: At a fixed IOP of 6 mm Hg, flow rate was measured by flow sensors. We validated the system by measuring the outflow responses to Y-39983 (a Rho kinase inhibitor), endothelin-1 (ET-1), ambrisentan (an antagonist for endothelin receptor A [ETA]), sphigosine-1-phosphate (S1P), JTE-013 (antagonist for S1P receptor 2 [S1P2]), S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide [NO] donor), and 3-Morpholino-sydnonimine (SIN-1, another NO donor). Results: The instrument design enabled simultaneous measurements of 20 eyes with a footprint of 1 m2. Relative to vehicle control, Y-39983 increased outflow by up to 31\% in calf eyes. On the contrary, ET-1 decreased outflow by up to 79\%, a response that could be blocked by pretreatment with ambrisentan, indicating a role for ETA receptors. Interestingly, the effect of ET-1 was also inhibited by up to 70\% to 80\% by pretreatment with NO donors, SNAP and SIN-1. In addition to testing in calf eyes, similar effects of ET-1 and ambrisentan were observed in adult bovine and porcine eyes. Conclusions: The compact eye perfusion platform provides an opportunity to efficiently identify compounds that influence outflow facility and may lead to the discovery of new glaucoma therapies.}, issn = {1552-5783}, doi = {10.1167/iovs.16-20974}, author = {Zhou, Enhua H. and Paolucci, Michael and Dryja, Thaddeus P and Manley, Ted and Xiang, Chuanxi and Rice, Dennis S and Prasanna, Ganesh and Chen, Amy} }