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Astrocyte remodeling without gliosis precedes optic nerve Axonopathy.
Acta Neuropathol Commun. 2018 05 10; 6(1):38.AN

Abstract

Astroyctes serve myriad functions but are especially critical in white matter tracts, where energy-demanding axons propagate action potentials great distances between neurons. Axonal dependence on astrocytes for even normal function accentuates the critical role astrocytes serve during disease. In glaucoma, the most common optic neuropathy, sensitivity to intraocular pressure (IOP) challenges RGC axons early, including degradation of anterograde transport to the superior colliculus (SC). Astrocyte remodeling presages overt axon degeneration in glaucoma and thus may present a therapeutic opportunity. Here we developed a novel metric to quantify organization of astrocyte processes in the optic nerve relative to axon degeneration in the DBA/2 J hereditary mouse model of glaucoma. In early progression, as axons expand prior to loss, astrocyte processes become more parallel with migration to the nerve's edge without a change in overall coverage of the nerve. As axons degenerate, astrocyte parallelism diminishes with increased glial coverage and reinvasion of the nerve. In longitudinal sections through aged DBA/2 J nerve, increased astrocyte parallelism reflected elevated levels of the astrocyte gap-junction protein connexin 43 (Cx43). In the distal nerve, increased Cx43 also indicated with a higher level of intact anterograde transport from retina to SC. Our results suggest that progression of axonopathy in the optic nerve involves astrocyte remodeling in two phases. In an early phase, astrocyte processes organize in parallel, likely through gap-junction coupling, while a later phase involves deterioration of organization as glial coverage increases and axons are lost.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The Vanderbilt Eye Institute, Vanderbilt University Medical Center, 1105 Medical Research Building IV, Nashville, TN, 37232-0654, USA.Department of Ophthalmology and Visual Sciences, The Vanderbilt Eye Institute, Vanderbilt University Medical Center, 1105 Medical Research Building IV, Nashville, TN, 37232-0654, USA.Department of Ophthalmology and Visual Sciences, The Vanderbilt Eye Institute, Vanderbilt University Medical Center, 1105 Medical Research Building IV, Nashville, TN, 37232-0654, USA. david.j.calkins@vanderbilt.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29747701

Citation

Cooper, Melissa L., et al. "Astrocyte Remodeling Without Gliosis Precedes Optic Nerve Axonopathy." Acta Neuropathologica Communications, vol. 6, no. 1, 2018, p. 38.
Cooper ML, Collyer JW, Calkins DJ. Astrocyte remodeling without gliosis precedes optic nerve Axonopathy. Acta Neuropathol Commun. 2018;6(1):38.
Cooper, M. L., Collyer, J. W., & Calkins, D. J. (2018). Astrocyte remodeling without gliosis precedes optic nerve Axonopathy. Acta Neuropathologica Communications, 6(1), 38. https://doi.org/10.1186/s40478-018-0542-0
Cooper ML, Collyer JW, Calkins DJ. Astrocyte Remodeling Without Gliosis Precedes Optic Nerve Axonopathy. Acta Neuropathol Commun. 2018 05 10;6(1):38. PubMed PMID: 29747701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Astrocyte remodeling without gliosis precedes optic nerve Axonopathy. AU - Cooper,Melissa L, AU - Collyer,John W, AU - Calkins,David J, Y1 - 2018/05/10/ PY - 2018/03/19/received PY - 2018/04/26/accepted PY - 2018/5/12/entrez PY - 2018/5/12/pubmed PY - 2019/5/31/medline KW - Astrocytes KW - Axonopathy KW - Connexin 43 KW - Glaucoma KW - Glia KW - Neurodegeneration KW - Retinal ganglion cell SP - 38 EP - 38 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 6 IS - 1 N2 - Astroyctes serve myriad functions but are especially critical in white matter tracts, where energy-demanding axons propagate action potentials great distances between neurons. Axonal dependence on astrocytes for even normal function accentuates the critical role astrocytes serve during disease. In glaucoma, the most common optic neuropathy, sensitivity to intraocular pressure (IOP) challenges RGC axons early, including degradation of anterograde transport to the superior colliculus (SC). Astrocyte remodeling presages overt axon degeneration in glaucoma and thus may present a therapeutic opportunity. Here we developed a novel metric to quantify organization of astrocyte processes in the optic nerve relative to axon degeneration in the DBA/2 J hereditary mouse model of glaucoma. In early progression, as axons expand prior to loss, astrocyte processes become more parallel with migration to the nerve's edge without a change in overall coverage of the nerve. As axons degenerate, astrocyte parallelism diminishes with increased glial coverage and reinvasion of the nerve. In longitudinal sections through aged DBA/2 J nerve, increased astrocyte parallelism reflected elevated levels of the astrocyte gap-junction protein connexin 43 (Cx43). In the distal nerve, increased Cx43 also indicated with a higher level of intact anterograde transport from retina to SC. Our results suggest that progression of axonopathy in the optic nerve involves astrocyte remodeling in two phases. In an early phase, astrocyte processes organize in parallel, likely through gap-junction coupling, while a later phase involves deterioration of organization as glial coverage increases and axons are lost. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/29747701/Astrocyte_remodeling_without_gliosis_precedes_optic_nerve_Axonopathy_ DB - PRIME DP - Unbound Medicine ER -