December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Intravitreal Endothelin-1 Significantly Decreases Slow Axonal Transport In Rat Optic Nerve
Author Affiliations & Notes
  • ME Stokely
    Dept Biomedical Sciences
    UNT Health Science Center Fort Worth TX
  • T Yorio
    Dept Biomedical Sciences and Dept Phamacology and Neuroscience
    UNT Health Science Center Fort Worth TX
  • Footnotes
    Commercial Relationships   M.E. Stokely, None; T. Yorio, None. Grant Identification: NIH Grant EY11979
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4034. doi:
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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)

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Abstract: : 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.

Keywords: 415 ganglion cells • 488 neuropeptides • 383 cytoskeleton 

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