Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes

Critical involvement of the leukocyte and 5-lipoxygenase metabolites in retinal capillary degeneration using a chimeric mouse model of diabetic retinopathy. Understanding the early pathogenesis of DR may uncover new therapeutic targets to prevent or slow the progression of this sight-threatening disorder. We investigated the role of leukocyte-mediated generation of LTs in regulation of retinal capillary degeneration and inflammation in the diabetic mouse. We generated (1) chimeric mice that lacked the ability to generate LTs by transplanting 5LO−/− bone marrow cells into ND.WT mice and into SD.WT mice and (2) “control” chimeric mice by transplanting WT bone marrow cells into 5LO−/− mice or into WT mice. Retinas from diabetic chimeric mice with WT marrow demonstrated capillary degeneration to the same extent as retinas from diabetic, nonchimeric WT mice. In contrast, retinas from diabetic chimeric mice with 5LO−/− marrow developed significantly less capillary degeneration and pericyte loss (P50% in diabetic chimeras containing 5LO−/− leukocytes (P