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Noriko Nakano, Hanako Ohashi Ikeda, Masanori Hangai, Yuki Muraoka, Yoshinobu Toda, Akira Kakizuka, Nagahisa Yoshimura; Longitudinal and Simultaneous Imaging of Retinal Ganglion Cells and Inner Retinal Layers in a Mouse Model of Glaucoma Induced by N-Methyl-d-Aspartate. Invest. Ophthalmol. Vis. Sci. 2011;52(12):8754-8762. doi: 10.1167/iovs.10-6654.
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To investigate the longitudinal profile of N-methyl-d-aspartate (NMDA) injection–induced damage in retinal ganglion cells (RGCs) by imaging retinal Thy 1-cyan fluorescent protein (CFP) expression and inner retinal layers using a custom-made imaging device containing short-wavelength confocal scanning laser ophthalmoscope (scSLO) and speckle noise–reduced spectral-domain optical coherence tomography (SD-OCT).
Simultaneous scSLO and SD-OCT examinations were performed in Thy 1-CFP mice injected with NMDA (1–20 nanomoles). CFP-expressing RGCs were counted using scSLO images. Ganglion cell complex (GCC: retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer) thickness around the optic disc was measured in SD-OCT images.
The RGCs rapidly decreased 1 day after NMDA injection in a dose-dependent manner (65.3%, 71.7%, 49.5%, and 27.1% of the preinjection level, 2, 5, 10, and 20 nanomoles, respectively) and continued to decrease slightly (to 53.7%, 44.1%, 28.3%, and 20.2% of the preinjection level on days 14, 2, 5, 10, and 20 nanomoles, respectively). In contrast, dose-dependent reduction of GCC thickness was first detected 4 days after injection. The thickness further decreased to 84.6%, 75.7%, 76.5%, and 71.4% of the preinjection level on day 14 (2, 5, 10, and 20 nanomoles, respectively).
NMDA-induced RGC damage is characterized by rapid RGCs loss followed by gradual reduction in GCC thickness. Simultaneous imaging of CFP expression in the RGCs and inner retinal layers provides a sensitive, reliable, and new method for longitudinal evaluation of progressive RGC damage in experimental models of glaucoma.
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