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Nemahun H Vincent, Hee Joo Choi, Tatjana C Jakobs, Daniel Sun; Expression of Lipocalin-2 in the Injured Optic Nerve. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3745. doi: https://doi.org/.
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Increased astrocyte reactivity has been noted in murine glaucoma models, while reactive astrocytes have been shown to produce lipocalin-2 (LCN2) following inflammatory stimulation of the central nervous system. However, it is not known if LCN2 is released by astrocytes in glaucomatous optic nerves nor if LCN2 is neurotoxic or neuroprotective in this context. Therefore, one aim of this study is to measure LCN2 expression in an experimental model of glaucoma. The second aim is to determine in which cells LCN2 is expressed and if such expression ameliorates or advances glaucomatous damage to the optic nerve.
C57BL/6J mice aged 2 to 4 months were used for this study. The models used included intraocular pressure (IOP) elevation via microbead injection into the anterior chamber of and optic nerve crush. LCN2 was localized using in-situ hybridization (RNAscope) and standardized immunohistochemistry techniques. qPCR was used to quantify LCN2 gene expression. Tissues from saline-injected and uninjured optic nerves served as controls.
Up-regulation of LCN2 is most pronounced at 4 hrs and 1 day post-crush. LCN2+ cells are abundantly localized at the pia/dura mater of the optic nerve and appear to migrate towards the crush site over time post-injury. By 8 days, the numbers of LCN2+ cells are significantly reduced and they are predominantly localized within the crush site. The LCN2+ cells do not co-localize with GFAP (astrocytes) or Iba1 (macrophages/microglia), but rather co-localize with CD45 and CD3, suggesting they are T cells.
Contrary to what has been observed in the CNS, LCN2 does not appear to be strongly expressed in reactive astrocytes. However, LCN2 is brought into the optic nerve by invading blood-borne cells, which have yet to be fully characterized. The recruitment of LCN2+ cells may play a role in axon degeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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