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Nobuharu Asai, Masayoshi Nakatani, Takao Nakamura, Kan Ohtsuki; Longitudinal Observation Of Retinal Thickness Using Spectral-domain Oct In Rabbit A New Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4995.
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N-methyl-D-aspartate (NMDA)-induced excitotoxicity of the rodent retina has been used in various studies of glaucoma. However, because of its smallness the rodent eye is unsuitable for studies of, for example, intraocular drug delivery devices, whereas the rabbit eye is a better size. We developed a more potent NMDA-induced retinal ganglion cell (RGC) loss model in the rabbit by using putrescine (a type of polyamine), and we investigated individual changes in retinal thickness by using optical coherence tomography (OCT).
Excitotoxic injury of the rabbit RGC was induced by a single injection NMDA alone or co-injection of NMDA and putrescine. Using spectral-domain (SD)-OCT (RS-3000; Nidek, Gamagori, Japan), we took images of visual streak region of each eye using the optic nerve head as a landmark. Baseline OCT images were obtained before the injection, and follow-up scans were obtained at 7 and 14 days post-injection. Fourteen days after the injection, the retinas were isolated and cells positive for Brn-3a (a marker of RGCs) were counted.
The ganglion cell complex (GCC) thickness of normal rabbit retina in the visual streak region was 51.2±1.6 μm. GCC thickness declined after NMDA injection (to 84.6% and 78.3% of pre-injection levels 7 and 14 days after injection, respectively). NMDA plus putrescine was more potent than NMDA injection alone in inducing a reduction in GCC thickness (to 77.2% and 60.9% of pre-injection levels 7 and 14 days after injection, respectively). The Brn-3a-positive RGC cell count indicated that there was more severe RGC loss with NMDA plus putrescine than with NMDA injection alone (to 22.2% and 69.7%, respectively, of the count with vehicle injection).
Putrescine enhanced the excitotoxic effects of NMDA in rabbits. This model is therefore more useful than models with NMDA alone for investigating RGC loss dynamics and therapeutic study. The use of SD-OCT to monitor inner retinal thickness will be valuable for various experiments, such as for testing therapeutic efficacy, because the same animals and the same region can be followed individually over time.
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