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Activated protein C rescues the retina from ischemia-induced cell death.

Authors: Du, ZJ  Yamamoto, T  Ueda, T  Suzuki, M  Tano, Y  Kamei, M 
Citation: Du ZJ, etal., Invest Ophthalmol Vis Sci. 2011 Feb 23;52(2):987-93. doi: 10.1167/iovs.10-5557.
Pubmed: (View Article at PubMed) PMID:20688738
DOI: Full-text: DOI:10.1167/iovs.10-5557

PURPOSE: Ischemia causes severe and persistent visual loss in many eye diseases, including central retinal vein occlusion (CRVO) and diabetic retinopathy. Activated protein C (APC) has been demonstrated to reduce the cell death associated with ischemia in the brain and kidney. This study was performed to examine the ability of APC to rescue hypoxia-induced retinal cell death in vitro and in vivo. METHODS: Retinal pigment epithelium (RPE) and photoreceptor cells were placed in either a normoxic or a hypoxic chamber. Immediately before they were subjected to ischemia, the cultures were treated with APC (3-240 mug/mL). Incubation was followed by an MTT assay to determine the number of viable cells. The activity of caspase-3, -8, and -9 in RPE cells was also analyzed. Various concentrations of APC were intravitreally injected in a rat CRVO model, followed by TUNEL staining to detect the in vivo effects of APC. RESULTS: Lower concentrations of APC (0.3-30 mug/mL) showed a cell-protective effect against hypoxia in vitro, whereas higher concentrations (>/=120 mug/mL) demonstrated cytotoxicity in both RPE and photoreceptor cells. Caspase-3, -8, and -9 were activated when the cells were exposed to hypoxia, but this activation was significantly inhibited by APC. Experimental CRVO-induced retinal cell apoptosis was reduced dramatically by intravitreal injection of APC. CONCLUSIONS: APC can reduce ischemia-induced cytotoxicity both in vitro and in vivo via blocking the activation of caspase-3, -8, and -9. APC may be a promising candidate for protecting the retina from ischemia.


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RGD Object Information
RGD ID: 11100028
Created: 2016-06-14
Species: All species
Last Modified: 2016-06-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.