Activation of caspase 9 in a rat model of experimental glaucoma.
OBJECTIVE
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.
Hänninen
Virve A
VA
Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Pantcheva
Mina B
MB
Freeman
Ellen E
EE
Poulin
Nathaniel R
NR
Grosskreutz
Cynthia L
CL
D000818:Animals; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D002452:Cell Count; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005901:Glaucoma / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000201:enzymology*; D013194:Staining and Labeling
D004792:Enzyme Precursors; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases