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alireza ghaffarieh, Christopher J Lieven, Leonard A Levin, William K McVicar; Evaluation of the neuroprotective effects of trabodenoson in a model of acute ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2427.
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Trabodenoson has been shown to lower intraocular pressure in humans with ocular hypertension or open-angle glaucoma (JS Myers, ARVO 2013 #2621). Glaucomatous vision loss is due to optic nerve neuropathy with consequent loss of retinal ganglion cells (RGCs). Adenosine is known to be neuroprotective in the brain via A1 receptor activation.1 In animals, adenosine has also been shown to protect the retina against ischemia.2 Trabodenoson, an adenosine mimetic selective for the A1 receptor, was investigated for its potential to protect RGCs in rats subjected to acute ocular hypertension.
Male Long Evans rats, 6 to 8 weeks old, were anesthetized and topical anesthetic applied to the cornea of the right eye, followed by two drops, 5 minutes apart, of 2.5% trabodenoson, 0.2% brimonidine, or vehicle. The anterior chamber was cannulated with a 30G needle attached to a saline reservoir and the pressure raised to 110 mmHg for 60 minutes. Animals were sacrificed 7 days later and the eyes and optic nerves were fixed and embedded in JB-4 for sagittal sectioning. Toluidine blue stained sections were imaged and the thickness of retinal layers were measured at each of 5 random locations. Images were captured and measurements performed using cellSens Dimension software on an Olympus BX61 microscope. Distances and counts in acutely hypertensive eyes were normalized to the mean of the naïve contralateral eye and compared by Student’s t-test.
Vehicle-treated animals (n = 10) showed a decrease in retinal thickness, most prominently in the inner retina (72 ± 5%, 66 ± 4%, and 85 ± 4% of paired naïve eyes in the ganglion cell, inner plexiform, and inner nuclear layers, respectively). Topical trabodenoson treatment (n = 10) significantly ameliorated the thinning in all three of these layers (100 ± 5%, p <0.001; 85 ± 3%, p < 0.001; and 96 ± 3%, p = 0.04, respectively). Brimonidine treatment (n = 10) was neuroprotective in the ganglion and inner plexiform layers only (94 ± 5%, p = 0.001; 79 ± 3%; p = 0.01: 90 ± 3%; p = 0.31).
Trabodenoson preserves inner retinal neurons in a rat model of acute optic hypertension. 1. Cunha, RA, Purinergic Signal. 2005; 1(2): 111-134; 2. Larsen AK, et al, Invest. Ophthalmol. Vis. Sci. 1996; 37:2603-2611.
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