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ME Stokely, T Yorio; Intravitreal Endothelin-1 Significantly Decreases Slow Axonal Transport In Rat Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4034.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Fibrillar changes, observed in peri-laminar axons from human glaucomatous donor tissue, suggest that a dysregulation in the anterograde slow axonal transport of filamentous material occurs in this disorder. Filamentous material is moved in both of the slow components of axonal transport. Slow component a (SCa) transports actin microfilaments while slow component b (SCb) transports microtubule segments, neurofilaments, and their associated proteins. Because elevated endothelins have been implicated as possible intermediaries in the development of glaucomatous optic neuropathy, this study examines the effects of intravitreal endothelin-1 on slow components of axonal transport. Methods: Sprague-Dawley rats were intravitreally injected with either a pharmacological dose of ET-1 (2 nmols) plus radiolabel (0.8 mCi of 35S Easy Tag methionine/cysteine protein labeling mix, ≷1000 Ci/mmol in 10 mM HEPES, pH 7.4), or radiolabel in vehicle only. After intervals of 4 days and 21 days, optic nerves were dissected, flash frozen, sectioned (2 mm segments), homogenized, and a 25% aliquot quantitated by liquid scintillation count. Corrected dpm values for segments 1-4 (segment 1 adjacent to the eye; segment 4 farthest from the eye) were evaluated by ANOVA (N=7), using Systat W 5 statistical software. Timepoints were selected based upon the published characterization of slow axonal transport in rat optic nerve. Results: Intravitreal ET-1 significantly decreased axonal transport at 4 days post-administration (SCb, actin microfilaments, reduced 50.3%), and at 21 days post-administration (SCa, microtubules and neurofilaments, reduced 28.1%), with p's =0.001 and 0.010, respectively. Effects on SCb were much greater than on SCa, indicating that ET-1's effects were either somewhat component-specific or partially reversible. Conclusion: Results were consistent with a role for elevated endothelins as glaucomatous intermediaries, causing peri-laminar fibrillar changes within retinal ganglion cell axons via dysregulation of slow axonal transport.
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