Topical Trabodenoson Is Neuroprotective in a Rodent Model of Anterior Ischemic Optic Neuropathy (rNAION)
| Autor: | Yan Guo, Rudolf A. Baumgartner, Steven L. Bernstein, David S Albers, Cadmus C Rich, Mary A. Johnson, Zara Mehrabian |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Intraocular pressure genetic structures adenosine receptor mimetics Biomedical Engineering Optic disk Glaucoma ischemia Retinal ganglion optic nerve 03 medical and health sciences 0302 clinical medicine Ophthalmology medicine Retina medicine.diagnostic_test business.industry astrocytes Articles medicine.disease eye diseases 3. Good health 030104 developmental biology medicine.anatomical_structure 030221 ophthalmology & optometry Optic nerve Anterior ischemic optic neuropathy neuroprotection sense organs nonarteritic anterior ischemic optic neuropathy (NAION) business edema Electroretinography |
| Zdroj: | Translational Vision Science & Technology |
| ISSN: | 2164-2591 |
| DOI: | 10.1167/tvst.8.6.47 |
| Popis: | Purpose 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(+) 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 = 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. |
| Databáze: | OpenAIRE |
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