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) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vincent, J. A. Articles by Mohr, S. Search for Related Content PubMed PubMed Citation Articles by Vincent, J. A. Articles by Mohr, S. Social Bookmarking                What's this?

Inhibition of Caspase-1/Interleukin-1ß Signaling Prevents Degeneration of Retinal Capillaries in Diabetes and Galactosemia

From the Department of Medicine, Center for Diabetes Research, Case Western Reserve University, Cleveland, Ohio

Address correspondence and reprint requests to Susanne Mohr, Case Western Reserve University, Department of Medicine, Division of Clinical and Molecular Endocrinology, Center for Diabetes Research, BRB 429, 10900 Euclid Ave., Cleveland, OH 44106. E-mail: sxm38{at}case.edu

Abbreviations: IL, interleukin; WT, wild-type

The proinflammatory cytokine, interleukin (IL)-1ß, is known to induce vascular dysfunction and cell death. We investigated the role of IL-1ß and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries. Caspase-1 activity is increased in retinas of diabetic and galactosemic mice and diabetic patients. First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1ß production and retinal capillary degeneration in diabetic and galactose-fed mice. Second, we examined the effect of genetic deletion of the IL-1ß receptor on diabetes-induced caspase activities and retinal capillary degeneration. Diabetic and galactose-fed mice were injected intraperitoneally with minocycline or tetracycline (5 mg/kg). At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1ß production in the retina. Long-term administration of minocycline prevented retinal capillary degeneration in diabetic (6 months) and galactose-fed (13 months) mice. Tetracycline inhibited hyperglycemia-induced caspase-1 activity in vitro but not in vivo. Mice deficient in the IL-1ß receptor were protected from diabetes-induced caspase activation and retinal pathology at 7 months of diabetes. These results indicate that the caspase-1/IL-1ß signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. V. Busik, S. Mohr, and M. B. Grant Hyperglycemia-Induced Reactive Oxygen Species Toxicity to Endothelial Cells Is Dependent on Paracrine Mediators Diabetes, July 1, 2008; 57(7): 1952 - 1965. [Abstract] [Full Text] [PDF]

				R. J. Walker and J. J. Steinle Role of {beta}-Adrenergic Receptors in Inflammatory Marker Expression in Muller Cells Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5276 - 5281. [Abstract] [Full Text] [PDF]