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Editors Selection IGR 15-4
Basic Research - LGN: Lateral geniculate nucleus defects in glaucomatous monkeys
Comment by Yeni Yucel on:
48991 An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation, Shimazawa M; Ito Y; Inokuchi Y et al., PLoS ONE, 2012; 7: e30526
In this interesting study, Shimazawa et al. detect in-vivo microglial activation using positron emission tomography (PET) imaging, one month after unilateral ocular hypertension (OHT) in four non-human primates. To visualize microglial activation, they intravenously injected [11C] PK11195, a radio-labeled ligand for the peripheral-type benzodiazepine receptor (PBR) prior to imaging. PET scan results obtained one month after OHT were compared with those obtained in the same animals before OHT. They found that the increase in PET signal in the LGN ipsilateral to the glaucomatous eye was significant, without a significant increase in signal in the contralateral LGN. Information regarding correlation between PET signal in LGNs and severity of glaucomatous damage was not disclosed.
Pathological correlates of in vivo PET scan were performed on postmortem LGN sections immunostained for peripheral-type benzodiazepine receptor, and were analyzed based on specific LGN layers unlike in vivo imaging of whole LGN. Although PBR expression was increased in layers driven by the glaucoma eye in both LGNs, it did not increase with glaucoma severity. The authors showed PBR immunoreactivity located in astrocytes and microglia.
As normal controls were not used in the neuropathological assessment, use of the fellow eye as a comparator likely underestimated some cellular change. In fact, degenerative changes1 and peroxynitrite- induced oxidative damage2 in LGN layers driven by the fellow non-glaucoma eye have been described in detail.
It is not clear whether activation of microglia is protective or destructive and this question needs further investigation at various disease stages. Additional controls to determine whether PK11195, a PBR receptor blocker, affects microglial activation and neural degeneration. PET is a very useful technology to study CNS changes in experimental glaucoma. Its potential use in human clinical trials is challenged by the need for systemic injection of a radioactive agent, in addition to images of lower resolution compared to those obtained with MRI. This study contributes significantly toward the development of neuroimaging markers. These biomarkers have the potential to be useful in clinical trials to help track disease progression, and assess treatment response in glaucoma.
References
- Yücel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N. Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin Eye Res 2003; 22: 465-481.
- Luthra A, Gupta N, Kaufman PL, Weinreb RN, Yücel YH. Oxidative injury by peroxynitrite in neural and vascular tissue of the lateral geniculate nucleus in experimental glaucoma. Exp Eye Res 2005; 80: 43-49.
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