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Panida Chindasub, Karen X. Duong-Polk, Chris K. Leung, James D. Lindsey, Robert N. Weinreb; Inhibition Of Histone Deacetylase-1 And -3 Protects Against Loss Of Fluorescence From Injured Fluorescent Retinal Neurons In Thy1-CFP Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2606.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the neuroprotective effects of MS-275 (an inhibitor of histone deacetylase-1 and -3) in preventing fluorescent retinal neuron loss following optic nerve crush in Thy1-cyan fluorescent protein (Thy1-CFP23Jrs) mice.
Thy1-CFP23Jrs mice were imaged using the blue-light confocal scanning laser ophthalmoscope (bCSLO) before and after optic nerve crush every week for 6 weeks. Mice were treated with 11.3 mg/kg MS-275 (sc) or vehicle 3x/wk starting 1 week before optic nerve crush and continuing for 6 weeks. Fluorescent spots in the same retinal area of each animal were counted manually.
The mean proportions of fluorescent retinal neurons remaining in the vehicle group at weeks 1 through 6 following optic nerve crush were 36.4±7.9, 18.5±6.4, 13.0±10.5, 12.1±4.1, 13.1±5.0, and 13.8±5.0 percent, respectively (n=6). The mean proportion of fluorescent retinal neurons remaining in the group treated with MS-275 were 59.3±18.9, 39.5±10.8, 34.0±12.4, 33.4±15.1, 31.7±12.5, and 26.9±15.0 percent at weeks 1-6, respectively (n=7, P<0.05 at weeks 1 through 5). Thus, the numbers of fluorescent cells in mice that received MS-275 were greater by 163%, 212%, 261%, 275%, 241%, and 194% at weeks 1 through 6 after optic nerve crush than in the control mice, respectively.
These results indicate MS-275 protects against loss of fluorescence from fluorescent retinal neurons in Thy1-CFP mice following optic nerve crush. Because fluorescent cells in these mice are predominantly retinal ganglion cells, these findings suggest there is a neuroprotective effect of MS-275 for retinal ganglion cells following optic nerve injury.
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