Details

Autor(en) / Beteiligte

• MOHR, Susanne
• XIA XI
• JIE TANG
• KERN, Timothy S

Titel

Caspase Activation in Retinas of Diabetic and Galactosemic Mice and Diabetic Patients

Ist Teil von

• Diabetes (New York, N.Y.), 2002-04, Vol.51 (4), p.1172-1179

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2002

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Caspase Activation in Retinas of Diabetic and Galactosemic Mice and Diabetic Patients Susanne Mohr 1 2 , Xia Xi 1 , Jie Tang 1 and Timothy S. Kern 1 2 1 Department of Medicine, Case Western Reserve University, Center for Diabetes Research, Cleveland, Ohio 2 Department of Opthamology, Case Western Reserve University, Center for Diabetes Research, Cleveland, Ohio Abstract Apoptosis of retinal capillary cells begins early in diabetes and likely contributes to the capillary obliteration that is an important feature of diabetic retinopathy. Caspases are proteolytic enzymes that are closely involved in the induction and execution phases of apoptosis, but their role in the development of diabetic retinopathy has not been studied previously. Our study focused on the measurement of activities of multiple caspases in retinas of mice at different durations of diabetes. Several caspases (including caspases-1, -2, -6, -8, and -9) were activated as early as 2 months of diabetes. The caspases activity pattern changed with increasing duration of disease, suggesting a slowly developing caspases cascade. Activities of executioner caspases (e.g., cas-6 and -3) became elevated after longer duration of diabetes, and the induction of cas-3 activity was associated with the duration of diabetes at which capillary cells begin to show evidence of undergoing apoptosis. Retinas from patients with type 2 diabetes likewise showed a significant increase in activities of cas-1, -3, -4, and -6. For comparison, retinal caspases were also measured in experimental galactosemia, another model that develops a diabetic-like retinopathy. The pattern of caspases activation differed between diabetes and galactosemia, but cas-1 activity became elevated soon after elevation of blood hexose concentration in both. Caspases offer new therapeutic targets to test the role of apoptosis in the development of diabetic retinopathy. Footnotes 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 435, 10900 Euclid Ave., Cleveland, OH 44106. E-mail: sxm38{at}po.cwru.edu . Received for publication 21 May 2001 and accepted in revised form 28 December 2001. BREC, bovine retinal endothelial cell; DMEM, Dulbecco’s modified Eagle’s medium; EBM, endothelial cell basal medium; FITC, fluorescein isothiocyanate; ECGF, endothelial cell growth factor; FBS, fetal bovine serum; rMC, retinal Müller cells; STZ, streptozotocin; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. DIABETES