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Caspase‐1/interleukin‐1beta signaling in diabetic retinopathy
Author(s) -
MOHR S
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.6114.x
Subject(s) - diabetic retinopathy , medicine , interleukin , interleukin 1β , immunology , ophthalmology , diabetes mellitus , cytokine , endocrinology
Purpose The pro‐inflammatory cytokine, interleukin‐1β (IL‐1β), is known to induce vascular dysfunction and cell death. Previously, we have shown that caspase‐1 activity is increased in retinas of diabetic and galactosemic mice, and diabetic patients. Therefore, we investigated the role of IL‐1β and caspase‐1 (the enzyme that produces it) in diabetes‐induced degeneration of retinal capillaries. Methods First, we determined the effect of agents known to inhibit caspase‐1 (minocycline and tetracycline) on IL‐1β production and retinal capillary degeneration in diabetic and galactose‐fed mice. Diabetic and galactose‐fed mice were injected intraperitoneally with minocycline or tetracycline (5mg/kg). Second, we examined the effect of genetic deletion of the IL‐1β receptor on diabetes‐induced caspase activities and retinal capillary degeneration using IL‐1 receptor knock‐out mice. Results At 2 months of diabetes, minocycline inhibited hyperglycemia‐induced caspase‐1 activity and IL‐1β 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‐1β receptor were protected from diabetes‐induced caspase activation and retinal pathology at 7 months of diabetes. Conclusion These results indicate that the caspase‐1/IL‐1β 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.