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Bruce A. Berkowitz, Leo Hawel, III, Craig Byus, David P. Bissig, Robin Roberts; Polyamines Contribute to Diabetic Retinal Edema. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5763.
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The single most common cause of severe vision loss in patients with diabetes is macular edema. Fundamental questions remain as to how such edema develops and how best to treat it. Patients with diabetes have elevated vitreous polyamine levels but it is uncertain if polyamines (i.e., putrescine, spermidine, spermine) are linked with retinal edema. In this study, we tested the hypothesis that ocular polyamines contribute to experimental diabetic retinal edema.
We studied 3 mo diabetic male Sprague Dawley (SD) rats with and without treatment of α-difluoromethylornithine (DFMO,200 mg/kg, 1x/day for a week, sq, a specific and irreversible inhibitor of the first and rate-limiting step in polyamine synthesis) and 2 mo diabetic male C57Bl/6 mice with and without systemic putrescine treatment (10 mg/kg, 2x/day for 1 week, SQ); age- and strain-matched controls were also examined. Outcome metrics included vitreous polyamine content (HPLC), central retinal thickness (MRI), and intraretinal water mobility profiles (diffusion-weighted MRI).
In diabetic male SD rats, a previously established model of diabetic retinal edema, vitreous spermidine and spermine, but not putrescine, levels were supernormal (P < 0.05). A direct correlation (P < 0.05) was found between polyamine content and central retinal thickness. In contrast, diabetic C57Bl/6 mice had thinner central retina than controls (P < 0.05). Within-retina changes in water mobility in vivo were consistent with the presence of edema in the diabetic rats and dehydration in the diabetic mice. DFMO intervention reduced (P < 0.05) supernormal central retinal thickness in diabetic male SD rats; exogenous putrescine increased (P < 0.05) subnormal central retinal thickness in diabetic mice.
These data highlight, for the first time, a role for polyamines in experimental diabetic retinal edema.
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