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Editors Selection IGR 15-4

Basic science: Caspases

Comment by Jonathan Crowston on:

12544 Transcriptional up-regulation and activation of initiating caspases in experimental glaucoma, Huang W; Dobberfuhl A; Filippopoulos T et al., American Journal of Pathology, 2005; 167: 673-681

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Caspases are proteolytic enzymes that disassemble a cell during apoptotic cell death. Caspase 8 and caspase 9 are upstream initiating caspases, activated by the extrinsic (cell surface death receptor) and intrinsic (mitochondrial) pathways respectively. Huang et al. (832) demonstrated cleaved forms of both activator caspases in retinal ganglion cells (RGC) of rats after ten days of IOP elevation. This indicates that both intrinsic and extrinsic apoptosis pathways are activated by IOP elevation in the rat. Acute caspase responses during apoptosis are regulated at the protein level by posttranslational modification leading to a proteolytic cascade of downstream caspase activation. The authors isolated retrograde-labeled RGCs by laser capture microscopy and using real-time PCR demonstrated that caspase 8 and caspase 9 mRNA is increased in the ocular hypertensive rat. These findings are important, as they suggest that elevated IOP leads to a coordinated program of transcriptional events leading to caspase upregulation, potentially priming RGCs to apoptosis.

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