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S. Oono, T. Kurimoto, Y. Tagami, R. Kashimoto, N. Okamoto, Y. Ito, O. Mimura; Pyroglutamic Acid Enhances Survival of Axotomized Retinal Ganglion Cells in Adult Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5507. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Pyroglutamic acid (PGA) is a cyclic derivative of glutamic acid and is present in a free form in the mammalian brain, eye, plasma, and cerebrospinal fluid. In cultures of primary cortical neurons, PGA reduces the neuronal cell death induced by glutamate toxicity which is due to the suppression of nitric oxide (NO). The purpose of this study was to determine whether PGA enhances the survival of axotomized retinal ganglion cells (RGCs) in vivo.
Rat RGCs were retrogradely labeled by placing sponges soaked with FluoroGold (FG) on both superior colliculi. Seven days after FG application, the left optic nerve was transected, and 2 µl of PGA in saline was immediately injected intravitreally. The concentrations of PGA were 0.5%, 1%, and 2%, and the vehicle was 2 µl saline. Seven days after optic nerve transection, both retinas were removed and flat-mounted. The number of FG-labeled RGCs in 12 areas of the flat-mounted retinas was counted under a fluorescence microscope, and the mean densities of FG-labeled RGCs were calculated.
The mean density of FG-labeled RGCs in the normal retinas was 2249±210/mm2. Seven days after optic nerve transection without any application, the mean densities of FG-labeled RGCs was reduced to 920 ± 202 /mm2. With PGA application, the mean densities of FG-labeled RGCs increased depending on the concentration of PGA. The mean densities of FG-labeled RGCs with 0.5% PGA was significantly higher at 1007±122/mm2 than in vehicle-treated eyes at 1213±159/mm2 (P=0.035). The mean densities with 1% and 2% PGA were further increased to 1464 ± 102/mm2 (P<0.001) and 1322±81/mm2 (P=0.001) compared to vehicle-treated eyes.
These results indicate that PGA enhances the survival of axotomized RGCs in adult rats. Further studies are needed to determine whether the neuroprotective effect of PGA is related to NO production or glutamate homeostasis after PGA intravitreal injection.
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