First Author | Chindasub P | Year | 2013 |
Journal | Invest Ophthalmol Vis Sci | Volume | 54 |
Issue | 1 | Pages | 96-102 |
PubMed ID | 23197683 | Mgi Jnum | J:214356 |
Mgi Id | MGI:5588798 | Doi | 10.1167/iovs.12-10850 |
Citation | Chindasub P, et al. (2013) Inhibition of histone deacetylases 1 and 3 protects injured retinal ganglion cells. Invest Ophthalmol Vis Sci 54(1):96-102 |
abstractText | PURPOSE: Thy-1 is a marker of retinal ganglion cell (RGC) differentiation. Optic nerve injury triggers reduction of Thy-1 promoter activation followed by retinal ganglion cell (RGC) death. This study determined whether MS-275, an inhibitor of the histone deacetylases 1 and 3, can inhibit these changes. METHODS: Mice expressing cyan fluorescent protein (CFP) under control of the Thy-1 promoter received MS-275 (subcutaneous) or vehicle three times per week starting 1 week before optic nerve crush and continuing for 6 weeks. The same retinal area was imaged using the blue-light confocal scanning laser ophthalmoscope before and after optic nerve crush every week, and fluorescent spots were counted manually. The eyes were then processed for histopathologic analysis. RESULTS: The mean proportions of fluorescent retinal neurons remaining in the vehicle group following optic nerve crush were 36 +/- 8, 18 +/- 6, 13 +/- 10, 12 +/- 4, 13 +/- 5, and 13 +/- 5% at weeks 1 through 6, respectively (n = 6). In contrast, the mean proportions of fluorescent retinal neurons remaining in the group treated with MS-275 were 59 +/- 19, 39 +/- 11, 34 +/- 12, 33 +/- 15, 32 +/- 13, and 27 +/- 15% at weeks 1 through 6, respectively (n = 7, P < 0.05 at weeks 1 through 5). Rate analysis showed that MS-275 slowed the rate of loss during the first 2 weeks by 23% (P < 0.05) and subsequently was similar. Histopathologic analysis revealed 27 +/- 13% greater ganglion cell layer (GCL) neurons in the eyes from mice that received MS-275 treatment (P < 0.02). CONCLUSIONS: These results indicate that treatment with MS-275 protects against the loss of RGC differentiation and promotes RGC survival following optic nerve injury. |