Cytoprotective Small Compound M109S Attenuated Retinal Ganglion Cell Degeneration Induced by Optic Nerve Crush in Mice

被引:1
作者
Scott-McKean, Jonah J. [1 ]
Matsuyama, Mieko [1 ]
Guo, Charles W. [1 ]
Ni, Lin [1 ]
Sassouni, Brandon [1 ]
Kurup, Shree [1 ]
Nickells, Robert [2 ]
Matsuyama, Shigemi [1 ,3 ,4 ,5 ]
机构
[1] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA
[2] Univ Wisconsin Madison, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA
[3] Case Western Reserve Univ, Sch Med, Dept Med Pharmacol, Div Hematol & Oncol, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA
[5] Case Comprehens Canc Ctr, Cleveland, OH 44106 USA
关键词
apoptosis; BAX; cell death inhibitor; nerve injury; PROAPOPTOTIC BAX; MOUSE MODEL; DEATH; NEURODEGENERATION; DYSFUNCTION; APOPTOSIS; PATHWAYS; GLAUCOMA; MARKER; TIME;
D O I
10.3390/cells13110911
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective small compound (CPSC) that inhibits BAX-mediated cell death. We examined whether M109S can protect RGC from optic nerve crush (ONC)-induced apoptosis. M109S was administered starting 5 h after ONC for 7 days. M109S was orally administered in two groups (5 mg/kg twice a day or 7.5 mg/kg once a day). The retina was stained with anti-BRN3A and cleaved Caspase-3 (active Caspase-3) that are the markers of RGC and apoptotic cells, respectively. ONC decreased the number of BRN3A-positive RGC and increased the number of active Caspase-3-expressing apoptotic cells. In ONC-treated retina, there were cells that were double stained with anti-BRN3A and ant-cleaved Caspase-3, indicating that apoptosis in BRN3A-positive RGCs occurred. M109S inhibited the decrease of BRN3A-positive cells whereas it inhibited the increase of active Caspase-3-positive cells in the retina of ONC-treated mice, suggesting that M109S inhibited apoptosis in RGCs. M109S did not induce detectable histological damage to the lungs or kidneys in mice, suggesting that M109S did not show toxicities in the lung or kidneys when the therapeutic dose was used. The present study suggests that M109S is effective in rescuing damaged RGCs. Since M109S is an orally bioactive small compound, M109S may become the basis for a portable patient-friendly medicine that can be used to prevent blindness by rescuing damaged optic nerve cells from death.
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页数:13
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