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dc.contributor.authorGuo, Y.
dc.contributor.authorMehrabian, Z.
dc.contributor.authorJohnson, M.A.
dc.contributor.authorBernstein, S.L.
dc.date.accessioned2020-02-04T16:19:39Z
dc.date.available2020-02-04T16:19:39Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85078128228&doi=10.1167%2ftvst.8.6.47&partnerID=40&md5=e7ec7ff8f0b64f91eaae313e74fb905d
dc.identifier.urihttp://hdl.handle.net/10713/11664
dc.description.abstractPurpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is the leading cause of sudden optic nerve–related vision loss currently without effective treatment. We evaluated the neuroprotective potential of ocular (topical) delivery of trabodenoson, a selective A1 receptor mimetic, in a rodent model of NAION (rNAION). Methods: Daily topical delivery of 3% trabodenoson or vehicle administered in both eyes 3 days prior to rNAION induction and for 21 days post induction. Retinal appearance and optic nerve head (ONH) edema was evaluated using spectral-domain optical coherence tomography (SD-OCT). Retinal function was evaluated before and after induction by ganzfeld electroretinography (ERG). Brn3a(þ) retinal ganglion cells (RGCs) were quantified by stereology. Axonal ultrastructure was evaluated by electron microscopy. Results: Trabodenoson-treated eyes had significantly reduced optic nerve (ON) edema compared with vehicle-treated eyes (ANOVA, P, 0.05). Electrophysiologically, there was a nonsignificant trend toward b-wave and oscillatory potential (OP) preservation in the trabodenoson-treated eyes. RGC counts were higher in trabodenoson-treated eyes compared to vehicle (74% versus 47% of the contralateral eye; two-tailed t-test; P ¼ 0.01), as were ON axons. No overt morphologic differences in cell inflammation were observed between vehicle-and trabodenoson-treated ONHs, but trabodenoson-treated ONHs revealed increased expression of astrocyte-related neuroprotective responses. Conclusions: Trabodenoson preserves RGCs in the rodent NAION model. While previous clinical trials focused on trabodenoson’s ocular antihypertensive effect, our data suggest trabodenoson’s primary target may be both the retina and ONH. Selective adenosine A1 agonists may prove an appropriate neuroprotective adjunctive for ischemia-related ON diseases such as NAION and glaucoma. Translational Relevance: RGC and ON neuroprotection in ischemic neuropathies may be achievable by topical administration of A1 adenosine agonists rather than by simply relying on intraocular pressure reduction.en_US
dc.description.sponsorshipThis study was initiated and partially funded by Inotek Pharmaceuticals. This study was also funded by National Institutes of Health Grant RO1-EY015304 (SLB).en_US
dc.description.urihttps://doi.org/10.1167/tvst.8.6.47en_US
dc.language.isoen_USen_US
dc.publisherAssociation for Research in Vision and Ophthalmology Inc.en_US
dc.relation.ispartofTranslational Vision Science and Technology
dc.subjectAdenosine receptor mimeticsen_US
dc.subjectAstrocytesen_US
dc.subjectEdemaen_US
dc.subjectIschemiaen_US
dc.subjectNeuroprotectionen_US
dc.subjectNonarteritic anterior ischemic optic neuropathy (NAION)en_US
dc.subjectOptic nerveen_US
dc.titleTopical trabodenoson is neuroprotective in a rodent model of anterior ischemic optic neuropathy (Rnaion)en_US
dc.typeArticleen_US
dc.identifier.doi10.1167/tvst.8.6.47


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