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Rose Anne Gubitosi-Klug, Reena Bapputty, Marcella Luercio, Njabulo Ngwenyama, Ramaprasad Talahalli; Diabetes-induced Changes in Leukotriene B4 Generation in Mice and Humans. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4902.
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© ARVO (1962-2015); The Authors (2016-present)
Prior work in our laboratory has implicated leukocytes and leukotriene generation as initiators of a damaging diabetes-induced inflammatory response in the retina. The purpose of the current study is to investigate 1) the role of LTB4 in the pathogenesis of early diabetic retinopathy in mice and 2) leukotriene B4 generation by isolated mouse and human leukocytes as a potential marker of early diabetic retinopathy.
Diabetes was induced with streptozotocin in wild-type mice and mice deficient in LTB4 generation. Leukocytes were isolated from diabetic and non-diabetic mice and assayed for stimulated LTB4 production. Retinas from all experimental groups of mice were analyzed for histologic changes consistent with early diabetic retinopathy. LTB4 generation assays were also performed on leukocytes from 17 control patients without diabetes and 26 patients with diabetes age 14-22 years and diabetes duration of 5-15 years and average HbA1c 8.9% (range 6.9% to 12.9%).
Despite similar degree of hyperglycemia, mice deficient in LTB4 production were protected from the typical diabetes-induced capillary degeneration and pericyte loss.(p < 0.05) Stimulation of leukocytes from diabetic wild-type mice showed a selective four-fold rise in LTB4 generation compared to leukocytes from non-diabetic mice and, as expected, leukocytes from diabetic mice deficient in LTB4 synthesis. Other pro-inflammatory eicosanoid levels, such as PGE2, were not altered by diabetes. Human leukocytes from young patients with diabetes duration of 5-15 years demonstrated as well an increase in LTB4 generation at 10-15 years diabetes duration compared to samples from non-diabetic patients and diabetic patients of shorter duration. (p < 0.009)
LTB4 plays an important role in the pathogenesis of diabetic retinopathy in our animal model. As in mice, LTB4 generation by leukocytes may be a potential biomarker for early diabetic retinopathy in humans.
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