HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Robertson, L. J. G. Articles by Azuma, M. Search for Related Content PubMed PubMed Citation Articles by Robertson, L. J. G. Articles by Azuma, M.

Calpain May Contribute to Hereditary Cataract Formation in Sheep

¹From the Agriculture and Life Sciences, Lincoln University, Canterbury, New Zealand; ²Research Laboratory, Senju Pharmaceutical Co., Ltd., Nishi-ku, Kobe, Japan; and ³Department of Integrative Biosciences, Oregon Health and Sciences University, Portland, Oregon.

PURPOSE. To determine the involvement of calpain in ovine cataractogenesis by measuring calcium, calpain activity, proteolysis, and the effect of calpain inhibition.

METHODS. Sheep with genetic cataracts were examined for cataract severity. Calcium in normal and cataract lenses was measured. The presence of calpain was detected by casein zymography and immunoblotting. Calpain activity was assayed using BODIPY-casein as a substrate. Degradation of calpain substrates spectrin and vimentin was assessed by immunoblotting. The calpain inhibitor SJA6017 was applied to the left eye of cataract lambs, leaving the right eye as an untreated control. Both eyes were monitored by slit-lamp microscopy for cataract progression.

RESULTS. Cortical cataracts were first observed in lambs at 1 to 2 months of age. Lens calcium concentration increased in the early stages of cataract formation and was >10-fold higher in mature cataract than normal lenses. Three calpain isoforms were detected in young lamb lenses. Calpain activity decreased as cataracts progressed. Both spectrin and vimentin were degraded with cataract maturity, which could indicate calpain proteolysis. Cataract lambs treated with SJA6017 eyedrops over a period of 4 months showed significantly smaller cataracts in the left treated eye over the right untreated eye.

CONCLUSIONS. The presence of calpains and calcium elevation during cataract formation suggests that proteolysis may play a role in opacification in ovine lens. This hypothesis is supported by the delay in opacification with SJA6017 treatment. The results also suggested that the ovine hereditary cataract is a useful nonrodent model to test the role of calpains in cataractogenesis.

This article has been cited by other articles:

				L. J. G. Robertson, L. L. David, M. A. Riviere, P. A. Wilmarth, M. S. Muir, and J. D. Morton Susceptibility of Ovine Lens Crystallins to Proteolytic Cleavage during Formation of Hereditary Cataract Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1016 - 1022. [Abstract] [Full Text] [PDF]

				X. Zhang, E. J. Dudek, B. Liu, L. Ding, A. F. Fernandes, J. J. Liang, J. Horwitz, A. Taylor, and F. Shang Degradation of C-terminal Truncated {alpha}A-crystallins by the Ubiquitin Proteasome Pathway Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4200 - 4208. [Abstract] [Full Text] [PDF]

				N. Nishikiori, M. Osanai, H. Chiba, T. Kojima, H. Ohguro, and N. Sawada Inhibitory Effects of Retinoic Acid Receptor Alpha Stimulants on Murine Cataractogenesis through Suppression of Deregulated Calpains Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2224 - 2229. [Abstract] [Full Text] [PDF]