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Masayuki Yasuda, Morin Ryu, Noriko Himori, Kazuko Omodaka, Ahmed Shanab, Jiro Takano, Takaomi Saido, Toru Nakazawa; The Role Of Calpain Pathway In Mice Models Of Normal Tension Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5441.
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© ARVO (1962-2015); The Authors (2016-present)
Calpain, an intracellular cysteine protease, has been reported to be widely involved in neuronal cell death. Axonal damage at the lamina cribrosa is thought to be an important contributor to retinal ganglion cell (RGC) death in glaucoma. The purpose of this study is to investigate the role of calpain activation in axonal damage-induced RGC death.
Wild-type mice (WT, 12 week-old, male, C57BL/6) and calpastatin, an endogenous inhibitor of calpain, knockout mice (CAST-KO) were used in this study. RGCs were retrogradely labeled by injecting a fluorescent tracer Fluoro-gold (FG) into the superior colliculus 7 days before the operation. Axonal damage was induced by optic nerve crash (NC) or tubulin destruction by leaving the spongel soaked with vinblastine (VB), a microtubule disassembly chemical, around the optic nerve. Seven days after axonal damage, the retinas were harvested and the flat-mounted retinas were prepared. The density of FG-labeled RGCs were assessed and compared between WT and CAST-KO. Additionally, a calpain inhibitor (SNJ1945, 100 mg/kg/day) was administered intraperitoneally and the density of surviving RGCs was compared with that of vehicle control group.
The mean density of surviving RGCs in CAST-KO was significantly decreased compared to that of WT both in NC (WT:1153 cells/mm2, CAST-KO:864 cells/mm2, p=0.0013) and VB (WT:1299 cells/mm2, CAST-KO:844 cells/mm2, p=0.0005). The mean density of surviving RGCs in SNJ1945-treated group was significantly higher than that of control (NC group: 1650 cells/mm2, p=0.0019; VB group 1825 cells/mm2, p=0.0005).
We demonstrate that calpain inhibitor has a neuroprotective effect against axonal damage-induced RGC death.
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