Abstract
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Objectives In glaucoma, the damage of retinal ganglion cells (RGCs) is accompanied with their axonal degradations and followed by transsynaptic neuronal cell death in the lateral geniculate nucleus (LGN). The progression of neural damages from peripheral to central visual pathways is critical in the glaucoma when determining therapeutic interventions. Therefore, in this study, to identify the spatiotemporal progression of neurodegeneration, we performed diffusion tensor magnetic resonance imaging (DTI) and microglia imaging by positron emission tomography (PET).
Methods Chronic intraocular pressure (IOP) elevation was induced by laser-trabeculoplasty in the left eyes of cynomolgus monkeys. IOP and ocular fundus were measured before and after the laser treatment with 1- or 2-week intervals. Microglial activation was detected by PET imaging with [11C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR) before and at 4 weeks after the laser treatment. DTI was also applied, and fractional anisotropy (FA) was calculated to estimate the density of viable neuronal axons and myelin.
Results In laser-treated eyes, IOP was persistently elevated throughout all observation periods. After the laser treatment, FA values decreased with elapsed time in the predicted visual pathways including the glaucomatous optic nerve. In addition, increase in [11C]PK11195 binding potential in the bilateral LGN was observed at 4 weeks after the laser treatment, in which activations of microglia in layers receiving input from the laser-treated eye were identified by immunostaining.
Conclusions In glaucoma, decrease in density of viable RGCs axon may progress with activation of microglia in the LGN, which may be critically involved in the transsynaptic neuronal degeneration