Calpain and Photoreceptor Apoptosis
Photoreceptor apoptosis is present in various retinopathies such as retinitis pigmentosa and glaucoma where caspases are generally considered to be the main executioners of apoptosis in various tissues. However, accumulating evidence suggests apoptosis could occur in a caspase-independent fashion. In this view, many studies have shown that calpain activation is associated with photoreceptor apoptosis in various animal and light-induced retinal degeneration models. Thus, calpain could be a potential target for treatment and may promote cell survival in cases where caspase inhibition has failed. Herein, we review current thinking on this topic and also present data showing protection of photoreceptors to apoptosis by systemic delivery of a calpain inhibitor in a light-induced model of retinal degeneration by modulation of the inner blood retina barrier (iBRB).
KeywordsCalpain Photoreceptor apoptosis Light-induced retinal damage Blood retina barrier Barrier modulation Claudin-5 Retinitis pigmentosa Age-related macular degeneration
We thank Caroline Woods, David Flynn and Rebecca Robertson for animal husbandry. The Ocular Genetics Unit at TCD is supported by Science Foundation Ireland, The Wellcome Trust, European Vision Institute, EVI-Genoret Grant LSHG-CT-2005-512036, Fighting Blindness Ireland and Enterprise Ireland.
- Shimazawa M, Suemori S, Inokuchi Y et al (2010) A novel calpain inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbony l)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther 332:380–387PubMedCrossRefGoogle Scholar