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Kota Sato, Yukihiro Shiga, Kazuko Omodaka, Shigeto Maekawa, Namie Murayama, Toru Nakazawa; Inhibition of Sp1 signaling promotes retinal ganglion cell death via apoptotic and necrotic pathways in a model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6008.
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© ARVO (1962-2015); The Authors (2016-present)
The transcription factor Sp1 is known to regulate both cell survival and cell death. In this study, we examined the role of Sp1 in retinal ganglion cell (RGC) death in a mouse model of glaucoma.
Optic nerve crush was performed under general anesthesia in the right eyes of C57BL / 6J mice (8-12 weeks old). Mithramycin, an Sp1 inhibitor, was administered intravitreally immediately after optic nerve crush. The retinal gene expression of cell death-related factors was determined with real-time PCR. Retinal cell death was examined with scanning laser ophthalmoscopy (F10, NIDEK) after the vitreous injection of Sytox (3.3 μM). The number of surviving RGCs was determined with immunohistochemistry for RBPMS, an RGC marker.
Two days after optic nerve crush, the retinal transcription levels of caspase-3 and c-Jun, known as apoptotic factors, rose significantly higher in the mithramycin administration group than in the control group. In addition, the gene expression of necroptotic factors, such as TNFa, TNF receptor-1, RIP1 and RIP3, also significantly increased in the mithramycin administration group. Moreover, an increase in the number of dead cells labeled with a Sytox probe was observed in the mithramycin administration group 5 days after optic nerve crush. The number of RBPMS-immunopositive RGCs also decreased in the retina 7 days after optic nerve crush.
Our results suggest that Sp1 activation after damage to the optic nerve works to protect against RGC dysfunction in a mouse model of glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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