The Experts below are selected from a list of 4980 Experts worldwide ranked by ideXlab platform

Timothy S Kern - One of the best experts on this subject based on the ideXlab platform.

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, Yunpeng Du, L. Zheng, C. Miller, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E 2 , superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling–positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P P P

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, L. Zheng, C. Miller, M Kim, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E(2), superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling-positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P < 0.05). Diabetes-induced activation of caspase-3 and -6 in retina was partially inhibited by Nepafenac (all P < 0.05). Oscillatory potential latency was the only abnormality of Retinal function reproducibly detected in these diabetic animals, and Nepafenac significantly inhibited this defect (P < 0.05). Nepafenac did not have a significant effect on diabetes-induced loss of cells in the ganglion cell layer or in corneal protease activity. Topical ocular administration of Nepafenac achieved sufficient drug delivery to the retina and diabetes-induced alterations in Retinal vascular Metabolism, function, and morphology were inhibited. In contrast, little or no effect was observed on diabetes-induced alterations in Retinal ganglion cell survival. Local inhibition of inflammatory pathways in the eye offers a novel therapeutic approach toward inhibiting the development of lesions of diabetic retinopathy.

  • abnormalities of Retinal Metabolism in diabetes and experimental galactosemia vii effect of long term administration of antioxidants on the development of retinopathy
    Diabetes, 2001
    Co-Authors: Renu A Kowluru, Jie Tang, Timothy S Kern
    Abstract:

    Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and α-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, α-tocopherol, N -acetyl cysteine, ascorbic acid, β-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% ( P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited (∼55–65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats ( P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of Retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

  • abnormalities of Retinal Metabolism in diabetes and experimental galactosemia vii effect of long term administration of antioxidants on the development of retinopathy
    Diabetes, 2001
    Co-Authors: Renu A Kowluru, Jie Tang, Timothy S Kern
    Abstract:

    Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and alpha-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% (P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited ( approximately 55-65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of Retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia viii prevention by aminoguanidine
    Current Eye Research, 2000
    Co-Authors: Renu A Kowluru, Ronald L Engerman, Timothy S Kern
    Abstract:

    Purpose. Aminoguanidine has been found to inhibit the development of some Retinal lesions in diabetic rats and diabetic dogs, thereby raising a possibility that the formation of glycation end products (AGEs) may be an essential step in the pathogenesis of the retinopathy. The purpose of this study is to investigate the effect of aminoguanidine administration on other metabolic abnormalities which might be involved in the development of retinopathy in two models of the retinopathy, alloxan diabetes and experimental galactosemia. Methods. Oxidative stress, nitric oxide (NO) and the activity of protein kinase C (PKC, total activity) were measured in the retina of the rats experimentally diabetic or galactosemic for 2 months. Effect of aminoguanidine administration on the inhibition of hyperglycemia-induced Retinal dysMetabolism was investigated. Results. Two months of diabetes or experimental galactosemia in rats resulted in elevation of Retinal oxidative stress (increase in thiobarbituric acid reactive subs...

David P Bingaman - One of the best experts on this subject based on the ideXlab platform.

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, Yunpeng Du, L. Zheng, C. Miller, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E 2 , superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling–positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P P P

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, L. Zheng, C. Miller, M Kim, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E(2), superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling-positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P < 0.05). Diabetes-induced activation of caspase-3 and -6 in retina was partially inhibited by Nepafenac (all P < 0.05). Oscillatory potential latency was the only abnormality of Retinal function reproducibly detected in these diabetic animals, and Nepafenac significantly inhibited this defect (P < 0.05). Nepafenac did not have a significant effect on diabetes-induced loss of cells in the ganglion cell layer or in corneal protease activity. Topical ocular administration of Nepafenac achieved sufficient drug delivery to the retina and diabetes-induced alterations in Retinal vascular Metabolism, function, and morphology were inhibited. In contrast, little or no effect was observed on diabetes-induced alterations in Retinal ganglion cell survival. Local inhibition of inflammatory pathways in the eye offers a novel therapeutic approach toward inhibiting the development of lesions of diabetic retinopathy.

Renu A Kowluru - One of the best experts on this subject based on the ideXlab platform.

  • abnormalities of Retinal Metabolism in diabetes and experimental galactosemia vii effect of long term administration of antioxidants on the development of retinopathy
    Diabetes, 2001
    Co-Authors: Renu A Kowluru, Jie Tang, Timothy S Kern
    Abstract:

    Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and α-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, α-tocopherol, N -acetyl cysteine, ascorbic acid, β-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% ( P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited (∼55–65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats ( P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of Retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

  • abnormalities of Retinal Metabolism in diabetes and experimental galactosemia vii effect of long term administration of antioxidants on the development of retinopathy
    Diabetes, 2001
    Co-Authors: Renu A Kowluru, Jie Tang, Timothy S Kern
    Abstract:

    Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and alpha-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% (P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited ( approximately 55-65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of Retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia viii prevention by aminoguanidine
    Current Eye Research, 2000
    Co-Authors: Renu A Kowluru, Ronald L Engerman, Timothy S Kern
    Abstract:

    Purpose. Aminoguanidine has been found to inhibit the development of some Retinal lesions in diabetic rats and diabetic dogs, thereby raising a possibility that the formation of glycation end products (AGEs) may be an essential step in the pathogenesis of the retinopathy. The purpose of this study is to investigate the effect of aminoguanidine administration on other metabolic abnormalities which might be involved in the development of retinopathy in two models of the retinopathy, alloxan diabetes and experimental galactosemia. Methods. Oxidative stress, nitric oxide (NO) and the activity of protein kinase C (PKC, total activity) were measured in the retina of the rats experimentally diabetic or galactosemic for 2 months. Effect of aminoguanidine administration on the inhibition of hyperglycemia-induced Retinal dysMetabolism was investigated. Results. Two months of diabetes or experimental galactosemia in rats resulted in elevation of Retinal oxidative stress (increase in thiobarbituric acid reactive subs...

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia v relationship between protein kinase c and atpases
    Diabetes, 1998
    Co-Authors: Renu A Kowluru, Ronald L Engerman, Michael R Jirousek, Lawrence E Stramm, Nagy A Farid, Timothy S Kern
    Abstract:

    In the retinas of diabetic animals, protein kinase C (PKC) activity is elevated, and Na+-K+-ATPase and calcium ATPase activities are subnormal. These abnormalities are also present in another model of diabetic retinopathy, experimental galactosemia. We have investigated the relationship between hyperglycemia-induced abnormalities of PKC and ATPases using a selective inhibitor of beta isoform of PKC (LY333531). Diabetes or experimental galactosemia of 2 months' duration resulted in > 50% elevation of PKC activity in the retina, and administration of LY333531 prevented the elevation. In retinas of the same rats, the LY333531 prevented hyperglycemia-induced decreases of both Na+-K+-ATPase and calcium ATPase activities. Retinal microvessels, the main site of lesions in diabetic retinopathy, likewise showed elevated activity of PKC and inhibition of ATPases in diabetes and in experimental galactosemia, and administration of LY333531 to diabetic animals prevented these abnormalities. PKC activity in sciatic nerves, in contrast, became subnormal in diabetes and experimental galactosemia, and LY333531 had no effect on PKC activity in the sciatic nerve. PKC activity in the cerebral cortex was not affected by diabetes or experimental galactosemia. The results suggest that diabetes-induced reductions in Na+-K+-ATPase and calcium ATPase in the retina are mediated in large part by PKC-beta. The availability of an agent that can normalize the hyperglycemia-induced increase in PKC activity in the retina should facilitate investigation of the role of PKC in the development of diabetic retinopathy.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia iv antioxidant defense system
    Free Radical Biology and Medicine, 1997
    Co-Authors: Renu A Kowluru, Timothy S Kern, Ronald L Engerman
    Abstract:

    Activities of enzymes that protect the retina from reactive oxygen species were investigated in experimentally diabetic rats and experimentally galactosemic rats, two animal models known to develop vascular lesions consistent with diabetic retinopathy. Diabetes or experimental galactosemia of 2 months duration significantly decreased the activities of glutathione reductase and glutathione peroxidase in the retina while having no effect on the glutathione synthesizing enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase. Activities of two other important antioxidant defense enzymes-superoxide dismutase (SOD) and catalase-also were decreased (by more than 25%) in retinas of diabetic rats and galactosemic rats. Administration of supplemental antioxidants, vitamins C and E, for the 2 months prevented the diabetes-induced impairment of antioxidant defense system in the retina. In experimentally galactosemic rats, the supplemental antioxidants were not as effective: SOD activity was normalized, but the enzymes of the glutathione redox cycle were only partly restored, and the subnormal catalase activity was unaffected. Diabetes or experimental galactosemia results in significant impairment of the antioxidant defense system in the retina, and exogenous antioxidant supplementation can help alleviate the subnormal activities of antioxidant defense enzymes.

Ronald L Engerman - One of the best experts on this subject based on the ideXlab platform.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia viii prevention by aminoguanidine
    Current Eye Research, 2000
    Co-Authors: Renu A Kowluru, Ronald L Engerman, Timothy S Kern
    Abstract:

    Purpose. Aminoguanidine has been found to inhibit the development of some Retinal lesions in diabetic rats and diabetic dogs, thereby raising a possibility that the formation of glycation end products (AGEs) may be an essential step in the pathogenesis of the retinopathy. The purpose of this study is to investigate the effect of aminoguanidine administration on other metabolic abnormalities which might be involved in the development of retinopathy in two models of the retinopathy, alloxan diabetes and experimental galactosemia. Methods. Oxidative stress, nitric oxide (NO) and the activity of protein kinase C (PKC, total activity) were measured in the retina of the rats experimentally diabetic or galactosemic for 2 months. Effect of aminoguanidine administration on the inhibition of hyperglycemia-induced Retinal dysMetabolism was investigated. Results. Two months of diabetes or experimental galactosemia in rats resulted in elevation of Retinal oxidative stress (increase in thiobarbituric acid reactive subs...

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia v relationship between protein kinase c and atpases
    Diabetes, 1998
    Co-Authors: Renu A Kowluru, Ronald L Engerman, Michael R Jirousek, Lawrence E Stramm, Nagy A Farid, Timothy S Kern
    Abstract:

    In the retinas of diabetic animals, protein kinase C (PKC) activity is elevated, and Na+-K+-ATPase and calcium ATPase activities are subnormal. These abnormalities are also present in another model of diabetic retinopathy, experimental galactosemia. We have investigated the relationship between hyperglycemia-induced abnormalities of PKC and ATPases using a selective inhibitor of beta isoform of PKC (LY333531). Diabetes or experimental galactosemia of 2 months' duration resulted in > 50% elevation of PKC activity in the retina, and administration of LY333531 prevented the elevation. In retinas of the same rats, the LY333531 prevented hyperglycemia-induced decreases of both Na+-K+-ATPase and calcium ATPase activities. Retinal microvessels, the main site of lesions in diabetic retinopathy, likewise showed elevated activity of PKC and inhibition of ATPases in diabetes and in experimental galactosemia, and administration of LY333531 to diabetic animals prevented these abnormalities. PKC activity in sciatic nerves, in contrast, became subnormal in diabetes and experimental galactosemia, and LY333531 had no effect on PKC activity in the sciatic nerve. PKC activity in the cerebral cortex was not affected by diabetes or experimental galactosemia. The results suggest that diabetes-induced reductions in Na+-K+-ATPase and calcium ATPase in the retina are mediated in large part by PKC-beta. The availability of an agent that can normalize the hyperglycemia-induced increase in PKC activity in the retina should facilitate investigation of the role of PKC in the development of diabetic retinopathy.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia iv antioxidant defense system
    Free Radical Biology and Medicine, 1997
    Co-Authors: Renu A Kowluru, Timothy S Kern, Ronald L Engerman
    Abstract:

    Activities of enzymes that protect the retina from reactive oxygen species were investigated in experimentally diabetic rats and experimentally galactosemic rats, two animal models known to develop vascular lesions consistent with diabetic retinopathy. Diabetes or experimental galactosemia of 2 months duration significantly decreased the activities of glutathione reductase and glutathione peroxidase in the retina while having no effect on the glutathione synthesizing enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase. Activities of two other important antioxidant defense enzymes-superoxide dismutase (SOD) and catalase-also were decreased (by more than 25%) in retinas of diabetic rats and galactosemic rats. Administration of supplemental antioxidants, vitamins C and E, for the 2 months prevented the diabetes-induced impairment of antioxidant defense system in the retina. In experimentally galactosemic rats, the supplemental antioxidants were not as effective: SOD activity was normalized, but the enzymes of the glutathione redox cycle were only partly restored, and the subnormal catalase activity was unaffected. Diabetes or experimental galactosemia results in significant impairment of the antioxidant defense system in the retina, and exogenous antioxidant supplementation can help alleviate the subnormal activities of antioxidant defense enzymes.

  • abnormalities of Retinal Metabolism in diabetes or experimental galactosemia iii effects of antioxidants
    Diabetes, 1996
    Co-Authors: Renu A Kowluru, Timothy S Kern, Ronald L Engerman, Donald Armstrong
    Abstract:

    Effects of antioxidants on hyperglycemia-induced alterations of Retinal Metabolism were evaluated in rats diabetic or experimentally galactosemic for 2 months. Oxidative stress was estimated by measuring lipid peroxides (measured as thiobarbituric acid reactive substances [TEARS]) in retina and plasma. Erythrocyte osmotic fragility, another measure of oxidative stress, also was determined in the same groups of rats. In diabetic rats, TBARS were elevated by 74% in retina and 87% in plasma. In galactose-fed rats, TBARS were significantly elevated in retina ( P + -K +- ATPase and calcium ATPase activities in retinas of diabetic animals without having any beneficial effect on plasma TBARS. In galactosemic rats, these antioxidants had a partial beneficial effect on the activity of Retinal Na + -K +- ATPase, but failed to have any effect on calcium ATPase. The beneficial effects of antioxidants in diabetes and experimental galactosemia were not caused by the amelioration of hyperglycemia or Retinal polyol accumulation. Erythrocyte osmotic fragility was increased by more than twofold in diabetes, but was normal in experimental galactosemia, and antioxidants prevented diabetes- induced increases in erythrocyte osmotic fragility. Diabetes-induced increased oxidative stress and subnormal ATPase activities in the retina can be inhibited by dietary supplementation with antioxidants.

C. Miller - One of the best experts on this subject based on the ideXlab platform.

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, Yunpeng Du, L. Zheng, C. Miller, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E 2 , superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling–positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P P P

  • topical administration of nepafenac inhibits diabetes induced Retinal microvascular disease and underlying abnormalities of Retinal Metabolism and physiology
    Diabetes, 2007
    Co-Authors: Timothy S Kern, Susanne Mohr, Sherry L Ball, Jeffrey A Jamison, L. Zheng, C. Miller, M Kim, David P Bingaman
    Abstract:

    Pharmacologic treatment of diabetic retinopathy via eyedrops could have advantages but has not been successful to date. We explored the effect of topical Nepafenac, an anti-inflammatory drug known to reach the retina when administered via eyedrops, on the development of early stages of diabetic retinopathy and on metabolic and physiologic abnormalities that contribute to the Retinal disease. Streptozotocin-induced diabetic rats were assigned to three groups (0.3% Nepafenac eyedrops, vehicle eyedrops, and untreated control) for comparison to age-matched nondiabetic control animals. Eyedrops were administered in both eyes four times per day for 2 and 9 months. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in Retinal prostaglandin E(2), superoxide, vascular endothelial growth factor (VEGF), nitric oxide (NO), cyclooxygenase-2, and leukostasis within Retinal microvessels. All of these abnormalities except NO and VEGF were significantly inhibited by Nepafenac. At 9 months of diabetes, a significant increase in the number of transferase-mediated dUTP nick-end labeling-positive capillary cells, acellular capillaries, and pericyte ghosts were measured in control diabetic rats versus nondiabetic controls, and topical Nepafenac significantly inhibited all of these abnormalities (all P < 0.05). Diabetes-induced activation of caspase-3 and -6 in retina was partially inhibited by Nepafenac (all P < 0.05). Oscillatory potential latency was the only abnormality of Retinal function reproducibly detected in these diabetic animals, and Nepafenac significantly inhibited this defect (P < 0.05). Nepafenac did not have a significant effect on diabetes-induced loss of cells in the ganglion cell layer or in corneal protease activity. Topical ocular administration of Nepafenac achieved sufficient drug delivery to the retina and diabetes-induced alterations in Retinal vascular Metabolism, function, and morphology were inhibited. In contrast, little or no effect was observed on diabetes-induced alterations in Retinal ganglion cell survival. Local inhibition of inflammatory pathways in the eye offers a novel therapeutic approach toward inhibiting the development of lesions of diabetic retinopathy.