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Optic nerve degeneration in the DBA/2NNia mouse: is the lamina cribrosa important in the development of glaucomatous optic neuropathy?

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Abstract

To study optic nerve (ON) degeneration in the DBA/2NNia (DBA) mouse, a species lacking a lamina cribrosa and a model for secondary angle-closure glaucoma, serial semi- and ultra-thin sectioning of the myelinated ON and of the ON head was performed and sections evaluated qualitatively and quantitatively by light and electron microscopy. Immunohistochemistry was performed using antibodies against collagen type I, III, VI, laminin, and connexin43. The major finding on the myelinated ON was a significant decrease in cross section area during ON degeneration which was paralleled by a loss of axons and an increase in microglia. The number of astrocytes and blood vessels did not change. The major findings on the ON papilla were that ON heads with only mild degeneration showed a pronounced focal degeneration around the central retinal artery. In more severely degenerated ON, newly formed bundles of collagen type VI were located between astrocyte processes within the ON head. In a species that has no lamina cribrosa, DBA mice can develop typical signs of glaucomatous optic neuropathy. The entrance of the central retinal vessels into the ONH seems to be a preferentially vulnerable region for axon loss in this mouse model. In addition, astrocytes in the ON head form extracellular material similar to that found in human glaucomatous eyes.

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Acknowledgements

Supported by SFB 539 (BII.2) from the DFG and NEI EY 15109, EY 13467, EY 01867.

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Authors and Affiliations

  1. Department of Anatomy, Carl Gustav Carus Medical Faculty, TU Dresden, Dresden, Germany

    Christian Albrecht May

  2. Department of Ophthalmology, Mount Sinai School of Medicine, New York, USA

    Thom Mittag

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  1. Christian Albrecht May
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  2. Thom Mittag
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Correspondence to Christian Albrecht May.

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May, C.A., Mittag, T. Optic nerve degeneration in the DBA/2NNia mouse: is the lamina cribrosa important in the development of glaucomatous optic neuropathy?. Acta Neuropathol 111, 158–167 (2006). https://doi.org/10.1007/s00401-005-0011-2

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  • DOI: https://doi.org/10.1007/s00401-005-0011-2

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