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Glaucoma pathology has been extensively studied at the level of the retinal ganglion cells (RGC) and optic nerve (ON). Measurements of intraocular pressure (IOP), ophthalmoscopy, and visual field have been mainly employed for the diagnosis of open-angle glaucoma (OAG). Recently, it has been reported that the RGC death is accompanied by transsynaptic degradation of neurons in the lateral geniculate nucleus (LGN), which is the primary processing center for visual information received from the retina, in glaucoma patients. In experimental glaucoma monkeys, it was suggested that neuronal atrophy in LGN may occur in the early stage after IOP elevation, and that LGN neurons may be more susceptible to the effects of IOP elevation than ON axons. Furthermore, it has been reported that in chronic hypertensive rats microglial activation is observed in both sides of the LGN during the early phase, at 1 week after IOP elevation, and this is most significant at 1 and 2 months. However, the pathophysiological process of LGN degeneration in glaucoma is as yet unknown. Here, we examined a possible early diagnosis of glaucoma on the basis of the LGN and ON degenerations in experimental glaucoma monkeys using a positron emission tomography (PET) and magnetic resonance imaging (MRI), respectively, and validated their changes by immunohistological examinations. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), and [(11)C]PK11195 binding potential was increased in the bilateral LGN at 4 weeks after IOP elevation. Diffusion MRI also showed the decreased density of ON axons at 4 weeks after IOP elevation. The present findings suggest that pathological changes occur in LGN and ON at an early glaucoma stage, and noninvasive molecular imaging in LGN and ON may be useful for early diagnosis of glaucoma.
H. Hara. Mol. Pharmacol., Gifu Pharmaceutical Uni., Gifu, Japan.
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)
2.16 Chiasma and retrochiasmal central nervous system (Part of: 2 Anatomical structures in glaucoma)