| First Author | Gubitosi-Klug RA | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 5 | Pages | 1387-93 |
| PubMed ID | 18346986 | Mgi Jnum | J:136092 |
| Mgi Id | MGI:3795073 | Doi | 10.2337/db07-1217 |
| Citation | Gubitosi-Klug RA, et al. (2008) 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes 57(5):1387-93 |
| abstractText | OBJECTIVE: Lipoxygenases are regulators of chronic inflammation and oxidative stress generation. We evaluated the role of 5- and 12-lipoxygenases in the development of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Wild-type mice, 5-lipoxygenase-deficient mice, and 12/15-lipoxygenase-deficient mice were assessed 1) after 9 months of diabetes for retinal histopathology and leukotriene receptor expression and 2) after 3 months of diabetes for leukostasis and retinal superoxide generation. RESULTS: Diabetic wild-type mice developed the expected degeneration of retinal capillaries and pericytes and increases in both leukostasis and superoxide production (P < 0.006). We found no evidence of diabetes-induced degeneration of retinal ganglion cells in these animals. The vascular histopathology was significantly inhibited in 5-lipoxygenase-deficient mice, but not in 12/15-lipoxygenase-deficient mice. Retinas from diabetic 5-lipoxygenase-deficient mice also had significantly less leukostasis, superoxide production, and nuclear factor-kappaB (NF-kappaB) expression (all P < 0.006), whereas retinas from diabetic 12/15-lipoxygenase-deficient mice had significantly less leukostasis (P < 0.005) but not superoxide production or NF- kappaB expression. Retinas from diabetic wild-type mice were enriched with receptors for the 5-lipoxygenase metabolite leukotriene B(4). Diabetes-induced histological and biochemical alterations were significantly reduced in 5-lipoxygenase-deficient mice, but not 12/15-lipoxygenase-deficient mice. CONCLUSIONS: 5-Lipoxygenase represents a novel pathway for therapeutic intervention of diabetic retinopathy. |
