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Cadmus C Rich, David Albers, Rebecca Fawcett, Yan Guo, Zara Mehrabyan, Rudolf Baumgartner, Steven L Bernstein; Neuroprotective efficacy of topical ocular delivery of trabodenoson in a rodent model of anterior ischemic optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1753.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the neuroprotective potential of ocular (topical) delivery of trabodenoson on the retina and optic nerve (ON) in a rodent model of anterior ischemic optic neuropathy (rAION).
Methods: Male Long-Evan rats (200-300 g) received twice daily ocular (topical) delivery of 3% trabodenoson (n=13) or vehicle (n=13) in both eyes starting 3 days prior to rAION induction and every day thereafter out to 21 days post induction. rAION was induced in right eye (OD) of anesthetized rats 30 sec following an intravenous injection of rose bengal dye (2.5 mM) by ON illumination (500 um spot size, 11 sec duration) via frequency-doubled Nd-YAG laser (532 nm) as previously described (Touitou et al (2013) IOVS 54, 7402). The left eye (OS) from each animal served as the control eye. Oscillation potentials (OPs) were recorded bilaterally 2-3 weeks post induction. Animals were euthanized 30 days post induction and perfused with paraformaldehyde. Retinal ganglion cells (RGCs) in post-fixed retinas were immunostained for Brn3a and quantified by stereology. ON tissue was either evaluated by immunolabeling for intact neurofilaments (SMI312) and inflammatory cells (IBA1), or fixed with glutaraldehyde and prepared for analysis by transmission electron microscopy (TEM).
Results: Electrophysiological results reveal that rAION reduced OPs in vehicle-treated eyes by approximately 50% of contralateral, control eyes. Comparatively, trabodenoson treatment significantly improved this rAION-induced reduction in OPs (33% of the control eyes, p=0.037). Preliminary results from RGC layer stereological cell counts in vehicle-treated eyes (n=6) indicate Brn3a-stained cells were reduced approximately 50%, whereas Brn3a-stained cells in trabodenoson-treated eyes (n=6) were only reduced by 33% (p=0.07 vs vehicle). Neurofilament immunolabeling of ON as well as TEM ultrastructural analysis suggests axonal preservation in the ON from trabodenoson-treated eyes as compared to vehicle treatment.
Conclusions: The electrophysiological results support a putative protective role for trabodenoson treatment in preserving RGC-inner retinal function in the rAION model. Preliminary results indicate that twice daily, ocular (topical) delivery of trabodenoson attenuates RGC loss and may preserve ON axonal fibers, as compared to vehicle treatment in this rodent model of NAION.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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