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Activation of caspase 9 in a rat model of experimental glaucoma
Virve A Hänninen1, Mina B Pantcheva, Ellen E Freeman
1Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Purpose:
We investigated retinal ganglion cell (RGC) death and activation of caspase 9 in rats with experimental glaucoma.
Methods:
Elevated intraocular pressure (IOP) was induced in rats using the Morrison model. Surviving backlabeled RGC were counted and TUNEL staining detected apoptosis. Procaspase 9 expression and activated caspase 9 were studied by immunoblot and immunohistochemistry.
Results:
IOP correlated with surviving RGC. TUNEL-positive RGC were observed in animals with elevated IOP. Procaspase 9 levels increased with IOP intensity. Cleaved caspase 9 was detected by immunoblot only in rats with peak IOP above 35 mm Hg for > or =6 days. Cleaved caspase 9 staining was seen only in the ganglion cell layer of retinas from rats with peak IOP > or =32 mm Hg.
Conclusions:
RGC loss is correlated with IOP in experimental glaucoma. These results support activation of caspase 9, the intrinsic caspase cascade, in RGC death in experimental glaucoma.