June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Chaperone peptides of α-crystallin inhibit cataract formation in rats
Author Affiliations & Notes
  • Rooban Nahomi
    Ophthalmology, Case Western Reserve University, Cleveland, OH
  • Benlian Wang
    Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH
  • Cibin Raghavan
    Ophthalmology, Case Western Reserve University, Cleveland, OH
  • Oliver Voss
    Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
  • Andrea Doseff
    Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
  • Puttur Santhoshkumar
    Ophthalmology, University of Missouri, Columbia, MO
  • Ram Nagaraj
    Ophthalmology, Case Western Reserve University, Cleveland, OH
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5753. doi:
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      Rooban Nahomi, Benlian Wang, Cibin Raghavan, Oliver Voss, Andrea Doseff, Puttur Santhoshkumar, Ram Nagaraj; Chaperone peptides of α-crystallin inhibit cataract formation in rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5753.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Peptides derived from the core domain of αA- (70KFVIFLDVKHFSPEDLTVK88) and αB-crystallin (73DRFSVNLDVKHFSPEELKVK92) have been shown to be chaperones. In a previous study on human lenses we found acetylated lysine residues in these peptides (K70 in αA and K92 in αB-crystallin). In this study we have investigated the anti-apoptotic and anti-cataractogenic effects of native and acetylated peptides in cultured cells and selenite-cataracts in rats.

Methods: The ability of the peptides to block apoptosis was tested in CHO and human lens epithelial cells. Apoptosis was induced by hyperthermia (43°C for 1 hr). Peptides were transferred to cells with the aid of a cationic lipid at 1, 2 and 4 µg/ml. We tested the peptides against calcimycin-induced apoptosis of lens epithelial cells in cultured mouse lenses. Anti-cataractogenic potential of the peptides was tested in sodium selenite-induced cataracts in rat pups. The peptides were administered by intraperitoneal (i.p.) injections at 2.5, 5 and 10 µg/animal 6 hr before selenite injection and on four consecutive days post-selenite injection. Total soluble proteins, βB1-crystallin content and markers of oxidative stress were measured.

Results: Both acetylated and native peptides of αA- and αB-crystallin showed protection against hyperthermia, but the former was 2-5% better than latter. Calcimycin-induced apoptosis of lens epithelial cells in organ-cultured lenses was inhibited by all peptides. Inhibition of apoptosis occurred as a result of a decrease mitochondrial release of cytochrome-C, inhibition of procaspase-3 activation and blockade of caspase-3 and -9 activities. The i.p. injected αB-acetylated peptide was detected in the lens by mass spectrometry. Administration of peptides completely blocked cataract development and at lower doses acetylated peptides were better than native peptides. The inhibition of cataract development was accompanied by blockade of apoptosis of lens epithelial cells, and inhibition of protein insolubilization and oxidative stress. A scrambled peptide of αA-crystallin showed none of the above effects.

Conclusions: Our results suggest that α-crystallin peptides are strong anti-apoptotic agents both in vitro and in vivo and they could be used as therapeutic agents in cataract, ischemic retinopathies and age-related macular degeneration, and in neurological diseases where apoptosis and/or protein aggregation are contributory factors.

Keywords: 488 crystallins • 426 apoptosis/cell death • 450 chaperones  
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