A Compact Whole-Eye Perfusion System to Evaluate Pharmacologic Responses of Outflow Facility.
Invest Ophthalmol Vis Sci
; 58(7): 2991-3003, 2017 06 01.
Article
em En
| MEDLINE
| ID: mdl-28605810
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Perfusão
/
Humor Aquoso
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Piridinas
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Malha Trabecular
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Glaucoma
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Pressão Intraocular
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article