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F. Paquet-Durand, J. McCall, D. Sanges, V. Marigo, T. van Veen, P. Ekstrom; Both Photoreceptor Cell Death and Survival Are Dependent on Calpain Activity. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2495.
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© ARVO (1962-2015); The Authors (2016-present)
The rd1-mouse displays an inherited retinal degeneration and allows studies of the mechanisms underlying the blinding disease retinitis pigmentosa (RP). Activation of calpain has been suggested to play an important role in rd1 photoreceptor cell death. However, little is known about the effects of calpain inhibition on photoreceptor survival. This study compares the effects of different types of calpain inhibitors and treatment paradigms on photoreceptor cell death.
Retinal explants were used to test for the effects of calpain inhibitors on photoreceptor survival in vitro in both short term and long term culture. In addition, in vivo intra vitreal injection of calpain inhibitors was performed. Calpain activity was determined using an in situ calpain activity assay and TUNEL staining was used to relate calpain activity to cell death.
Acute, short term inhibition of calpains protected photoreceptors against rd1 induced cell death, while long term, chronic inhibition had detrimental effects, particularly on photoreceptors. Other parts of the retina, such as the ganglion cell layer, were less affected by calpain inhibition.
The effects of calpain inhibition are highly dependent on the exact experimental paradigm used and can be both destructive and protective. Thus, activation of calpains plays an important role in promoting both the survival and death of photoreceptor cells. The differential effects of calpain inhibition could be due to the activation of different calpain isoforms in different subcellular compartments. While calpain inhibitors might be effective in preventing photoreceptor degeneration under certain circumstances, caution with their indiscriminate use is advisable.
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