5-Lipoxygenase, but not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy. Export

@article{citeulike:2569391, abstract = {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 (WT) mice, 5-lipoxygenase-deficient (5-LO) mice, and 12/15-lipoxygenase-deficient (12-LO) 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 WT 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-LO-deficient mice, but not in 12-LO-deficient mice. Retinas from diabetic 5-LO deficient mice also had significantly less leukostasis, superoxide production and NF-kappaB expression (all p<0.006), whereas retinas from diabetic 12-LO-deficient mice had significantly less leukostasis (P<0.005) but not superoxide production or NF-kappaB expression. Retinas from diabetic wt mice were enriched with receptors for the 5-lo metabolite leukotriene b(4). Conclusions: Diabetes-induced histological and biochemical alterations were significantly reduced in 5-LO-deficient mice, but not 12-LO-deficient mice. 5-LO represents a novel pathway for therapeutic intervention of diabetic retinopathy.}, address = {Department of Pediatrics, Case Western Reserve University/Rainbow Babies and Children's Hospital, Cleveland, OH.}, author = {Gubitosi-Klug, Rose A A. and Talahalli, Ramaprasad and Du, Yunpeng and Nadler, Jerry L L. and Kern, Timothy S S.}, citeulike-article-id = {2569391}, citeulike-linkout-0 = {http://dx.doi.org/10.2337/db07-1217}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18346986}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18346986}, day = {17}, doi = {10.2337/db07-1217}, issn = {1939-327X}, journal = {Diabetes}, keywords = {5-lox, angiogenesis, diabetes}, month = {March}, posted-at = {2008-03-31 03:22:34}, priority = {2}, title = {5-Lipoxygenase, but not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy.}, url = {http://dx.doi.org/10.2337/db07-1217}, year = {2008} }

TY - JOUR ID - citeulike:2569391 L3 - citeulike-article-id:2569391 N2 - 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 (WT) mice, 5-lipoxygenase-deficient (5-LO) mice, and 12/15-lipoxygenase-deficient (12-LO) 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 WT 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-LO-deficient mice, but not in 12-LO-deficient mice. Retinas from diabetic 5-LO deficient mice also had significantly less leukostasis, superoxide production and NF-kappaB expression (all p<0.006), whereas retinas from diabetic 12-LO-deficient mice had significantly less leukostasis (P<0.005) but not superoxide production or NF-kappaB expression. Retinas from diabetic wt mice were enriched with receptors for the 5-lo metabolite leukotriene b(4). Conclusions: Diabetes-induced histological and biochemical alterations were significantly reduced in 5-LO-deficient mice, but not 12-LO-deficient mice. 5-LO represents a novel pathway for therapeutic intervention of diabetic retinopathy. JF - Diabetes SN - 1939-327X AD - Department of Pediatrics, Case Western Reserve University/Rainbow Babies and Children's Hospital, Cleveland, OH. TI - 5-Lipoxygenase, but not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy. KW - 5-lox KW - angiogenesis KW - diabetes AU - Gubitosi-Klug, Rose A AU - Talahalli, Ramaprasad AU - Du, Yunpeng AU - Nadler, Jerry L AU - Kern, Timothy S PY - 2008/03/17/ UR - http://dx.doi.org/10.2337/db07-1217 ER -