title: Role of calpains in diabetes mellitus-induced cataractogenesis: a mini review.
abstract: Premature visual impairment due to lens opacification is a debilitating characteristic of untreated diabetes. Lens opacification is primarily due to the insolubilization of crystallins, proteins essential for lens optical properties, and recent studies have suggested that a major cause of this insolubilization may be the unregulated proteolysis of crystallins by calpains. These are intracellular cysteine proteases whose activation requires the presence of calcium (Ca2+) and elevated levels of lens Ca2+ is a condition associated with both diabetic cataractogenesis and other forms of the disorder. A number of calpains have been identified in the lens, including calpain 2, calpain 10 and two isozymes of calpain 3: Lp82 and Lp85. The use of animal hereditary cataract models have suggested that calpain 2 and/or Lp82 may be the major calpains involved in murine cataractogenesis with contributions from calpain 10 and Lp85. However, calpain 2 appears to be the major calpain involved in murine diabetic cataractogenesis and the strongest candidate of the calpains for a role in human types of cataractogenesis. Here, we present an overview of recent evidence on which these observations are based with an emphasis on the ability of calpains to proteolyse lens crystallins and calpain structural features, which appear to be involved in the Ca2+-mediated activation of these enzymes.
authors.affiliation: Department of Ophthalmology, Royal Preston Hospital, Preston, PR2 9HT, England, UK.
authors.forename: Suman
authors.initials: S
authors.lastname: Biswas
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
authors.forename: Jaipaul
authors.initials: J
authors.lastname: Singh
authors.forename: David
authors.initials: D
authors.lastname: Phoenix
mesh_terms: D002154:Calpain / Q000378:metabolism / Q000502:physiology*; D002386:Cataract / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D048909:Diabetes Complications / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology
chemical_list: D002154:Calpain