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Editors Selection IGR 15-4
Basic Research: Astrocyte reactivity and microglial activation
Comment by Yeni Yucel on:
25428 Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates., Lam D; Jim J; To E et al., Molecular Vision, 2009; 15: 2217-2229
Lam et al. (53) study early astrocytic reactivity and microglial activation in the lateral geniculate nucleus (LGN) and visual cortex in ocular hypertensive (OHT) monkeys for up to two months. Sections of the LGN and visual cortex were immunostained with glial fibrillary acidic protein (GFAP) and CD11b (a component of the complement receptor 3b), and markers for astrocytes and microglia, respectively. Background, moderate and robust immunostaining for these markers were described in tissues driven by eye with OHT compared to those driven by the fellow eye.
This study demonstrates astrocytic activation in the visual cortex in early OHT and corroborates previously described glial activation in the LGN in OHT monkeys.1
In this study, microglial activation was not noted in either the LGN or visual cortex (n = 3; Table 1). This is different from an in-vivo study that detected microglia activation by PET with radioactive PK11195 as well as immunostaining for microglia in OHT monkeys.2 Further studies are needed to better understand the temporal course of microglia activation using a larger sample size and multiple markers of microglial activation.3
Unlike the OHT monkeys, the authors found microglial activation in the LGN and primary visual cortex in three animals with optic nerve transection. In view of the active blood-brain barrier disruption and Wallerian degeneration in this model, it is unclear to what extent CD11b is identifying parenchymal microglia or blood-born macrophages in perivascular spaces 4-6 Further studies using CD14 and CD45 will help to clarify this.
Previous work has demonstrated that LGN layers connected to the fellow non-glaucomatous eye undergo degeneration. In this study, since normal controls were not used, it is possible that the use of the fellow eye as a comparator underestimated some of the cellular changes.7 Further studies of inflammatory responses in central visual pathways in glaucoma are needed to investigate whether they are friend or foe at various stages of the disease.
References
- Sasaoka M, Nakamura K, Shimazawa M, Ito Y, Araie M, Hara H. Changes in visual fields and lateral geniculate nucleus in monkey laser-induced high intraocular pressure model. Exp Eye Res 2008; 86:770-82.
- Imamura K, Onoe H, Shimazawa M, Nozaki S, Wada Y, Kato, K, Nakajima H, Mizuma H, Onoe K, Taniguchi T, Sasaoka, M, Hara H, Tanaka S, Araie M, Watanabe Y. Molecular imaging reveals unique degenerative changes in experimental glaucoma. Neuroreport 2009; 20:139-44.
- Shawn F. Sorrells and Robert M. Sapolsky. An Inflammatory Review of Glucocorticoid Actions in the CNS. Brain Behav Immun. 2007; 21: 259-272.
- Ulvestad E, Williams K, Mork S, Antel J, Nyland H: Phenotypic differences between human monocytes/macrophages and microglial cells studied in situ and in vitro. J Neuropathol Exp Neurol 1994; 53:492-501
- Ulvestad E, Williams K, Bjerkvig R, Tiekotter K, Antel J, Matre R: Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. J Leukoc Biol 1994; 56:732-740
- Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V: Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system, Proc Natl Acad Sci USA 1991; 88:7438-7442
- Y.H. Yücel, Q. Zhang, R.N. Weinreb, P.L. Kaufman, N. Gupta. Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Progress in Retinal and Eye Research 2003; 22: 465-481,.
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