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Journal of Diabetes Research
Volume 2013 (2013), Article ID 425854, 8 pages
http://dx.doi.org/10.1155/2013/425854
Review Article

Zinc and Diabetic Retinopathy

1The Second Hospital of Jilin University, Changchun 130021, China
2Department of Ophthalmology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
3The First Hospital of Jilin University, Changchun 130021, China
4Department of Cardiovascular Disease, The First Hospital of Jilin University, Changchun, Jilin 130021, China

Received 11 January 2013; Accepted 8 February 2013

Academic Editor: Weiping Jia

Copyright © 2013 Xiao Miao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. E. Coleman, “Zinc Proteins: enzymes, storage proteins, transcription factors, and replication proteins,” Annual Review of Biochemistry, vol. 61, pp. 897–946, 1992. View at Scopus
  2. B. L. Vallee and K. H. Falchuk, “The biochemical basis of zinc physiology,” Physiological Reviews, vol. 73, no. 1, pp. 79–118, 1993. View at Scopus
  3. L. Cai, X. K. Li, Y. Song, and M. G. Cherian, “Essentiality, toxicology and chelation therapy of zinc and copper,” Current Medicinal Chemistry, vol. 12, no. 23, pp. 2753–2763, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. R. D. Palmiter and S. D. Findley, “Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc,” EMBO Journal, vol. 14, no. 4, pp. 639–649, 1995. View at Scopus
  5. L. A. Gaither and D. J. Eide, “The human zip1 transporter mediates zinc uptake in human k562 erythroleukemia cells,” Journal of Biological Chemistry, vol. 276, no. 25, pp. 22258–22264, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Kambe, Y. Yamaguchi-Iwai, R. Sasaki, and M. Nagao, “Overview of mammalian zinc transporters,” Cellular and Molecular Life Sciences, vol. 61, no. 1, pp. 49–68, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. R. D. Palmiter, “Protection against zinc toxicity by metallothionein and zinc transporter 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 14, pp. 4918–4923, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. J. P. Liuzzi and R. J. Cousins, “Mammalian zinc transporters,” Annual Review of Nutrition, vol. 24, pp. 151–172, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. Z. Zhou, X. Sun, and Y. James Kang, “Metallothionein protection against alcoholic liver injury through inhibition of oxidative stress,” Experimental Biology and Medicine, vol. 227, no. 3, pp. 214–222, 2002. View at Scopus
  10. L. Cai, “Metallothionein as an adaptive protein prevents diabetes and its toxicity,” Nonlinearity in Biology, Toxicology and Medicine, vol. 2, pp. 89–103, 2004.
  11. P. Lefèbvre, “Diabetes yesterday, today and tomorrow. The action of the Internation Diabetes Federation,” Revue Medicale de Liege, vol. 60, no. 5-6, pp. 273–277, 2005. View at Scopus
  12. National Estimates and General Information on Diabetes and Prediabetes in the United States, Centers for Disease Control and Prevention, Atlanta, Ga, USA, 2011.
  13. R. Klein, B. E. K. Klein, S. E. Moss, and K. J. Cruickshanks, “The wisconsin epidemiologic study of diabetic retinopathy: XVII. The 14- year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes,” Ophthalmology, vol. 105, no. 10, pp. 1801–1815, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. N. Cheung, P. Mitchell, and T. Y. Wong, “Diabetic retinopathy,” The Lancet, vol. 376, no. 9735, pp. 124–136, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. S. R. Powell, “The antioxidant properties of zinc,” Journal of Nutrition, vol. 130, pp. 1447S–1454S, 2000.
  16. Y. Adachi, J. Yoshida, Y. Kodera et al., “Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes,” Biochemical and Biophysical Research Communications, vol. 351, no. 1, pp. 165–170, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. D. M. Alscher, N. Braun, D. Biegger et al., “Induction of metallothionein in proximal tubular cells by zinc and its potential as an endogenous antioxidant,” Kidney and Blood Pressure Research, vol. 28, no. 3, pp. 127–133, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. J. W. Baynes and S. R. Thorpe, “Role of oxidative stress in diabetic complications: a new perspective on an old paradigm,” Diabetes, vol. 48, no. 1, pp. 1–9, 1999. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Piconi, L. Quagliaro, and A. Ceriello, “Oxidative stress in diabetes,” Clinical Chemistry and Laboratory Medicine, vol. 41, no. 9, pp. 1144–1149, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. R. A. Kowluru, J. Tang, and T. S. Kern, “Abnormalities of retinal metabolism in diabetes and experimental galactosemia. Vii. Effect of long-term administration of antioxidants on the development of retinopathy,” Diabetes, vol. 50, no. 8, pp. 1938–1942, 2001. View at Scopus
  21. R. A. Kowluru and A. Kennedy, “Therapeutic potential of anti-oxidants and diabetic retinopathy,” Expert Opinion on Investigational Drugs, vol. 10, no. 9, pp. 1665–1676, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Brownlee, “The pathobiology of diabetic complications: a unifying mechanism,” Diabetes, vol. 54, no. 6, pp. 1615–1625, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. S. E. Bursell, A. C. Clermont, L. P. Aiello et al., “High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes,” Diabetes Care, vol. 22, no. 8, pp. 1245–1251, 1999. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Nebbioso, M. Federici, D. Rusciano, M. Evangelista, and N. Pescosolido, “Oxidative stress in preretinopathic diabetes subjects and antioxidants,” Diabetes Technology and Therapeutics, vol. 14, no. 3, pp. 257–263, 2012. View at Publisher · View at Google Scholar
  25. A. E. Millen, M. Gruber, R. Klein, B. E. K. Klein, M. Palta, and J. A. Mares, “Relations of serum ascorbic acid and α-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey,” American Journal of Epidemiology, vol. 158, no. 3, pp. 225–233, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Kanwar, P. S. Chan, T. S. Kern, and R. A. Kowluru, “Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase,” Investigative Ophthalmology and Visual Science, vol. 48, no. 8, pp. 3805–3811, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. T. M. Bray and W. J. Bettger, “The physiological role of zinc as an antioxidant,” Free Radical Biology and Medicine, vol. 8, no. 3, pp. 281–291, 1990. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Jomova and M. Valko, “Advances in metal-induced oxidative stress and human disease,” Toxicology, vol. 283, no. 2-3, pp. 65–87, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. A. S. Prasad, “Zinc: role in immunity, oxidative stress and chronic inflammation,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 12, no. 6, pp. 646–652, 2009. View at Publisher · View at Google Scholar
  30. A. S. Prasad, “Clinical, immunological, anti-inflammatory and antioxidant roles of zinc,” Experimental Gerontology, vol. 43, no. 5, pp. 370–377, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. R. M. Walter, J. Y. Uriu-Hare, K. L. Olin et al., “Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus,” Diabetes Care, vol. 14, no. 11, pp. 1050–1056, 1991. View at Scopus
  32. S. A. Moustafa, “Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats,” Toxicology and Applied Pharmacology, vol. 201, no. 2, pp. 149–155, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. A. M. Roussel, A. Kerkeni, N. Zouari, S. Mahjoub, J. M. Matheau, and R. A. Anderson, “Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus,” Journal of the American College of Nutrition, vol. 22, no. 4, pp. 316–321, 2003. View at Scopus
  34. B. D. A. Calesnick, “Zinc deficiency and zinc toxicity,” American Family Physician, vol. 37, pp. 267–270, 1988.
  35. M. Ugarte, G. W. Grime, G. Lord et al., “Concentration of various trace elements in the rat retina and their distribution in different structures,” Metallomics, vol. 4, pp. 1245–1254, 2012.
  36. J. M. Rogers and L. S. Hurley, “Effects of zinc deficiency on morphogenesis of the fetal rat eye,” Development, vol. 99, no. 2, pp. 231–238, 1987. View at Scopus
  37. B. H. Grahn, P. G. Paterson, K. T. Gottschall-Pass, and Z. Zhang, “Zinc and the eye,” Journal of the American College of Nutrition, vol. 20, no. 2, pp. 106–118, 2001. View at Scopus
  38. S. J. Muga and A. Grider, “Partial characterization of a human zinc-deficiency syndrome by differential display,” Biological Trace Element Research, vol. 68, no. 1, pp. 1–12, 1999. View at Scopus
  39. S. K. Pati and R. Mukherji, “Serum zinc in corneal ulcer—a preliminary report,” Indian Journal of Ophthalmology, vol. 39, no. 3, pp. 134–135, 1991. View at Scopus
  40. M. B. Berman and R. Manabe, “Corneal collagenases: evidence for zinc metalloenzymes,” Annals of Ophthalmology, vol. 5, no. 11, pp. 1193–1209, 1973. View at Scopus
  41. S. A. Morrison, R. M. Russell, E. A. Carney, and E. V. Oaks, “Zinc deficiency: a cause of abnormal dark adaptation in cirrhotics,” American Journal of Clinical Nutrition, vol. 31, no. 2, pp. 276–281, 1978. View at Scopus
  42. H. I. Afridi, T. G. Kazi, N. Kazi et al., “Evaluation of status of zinc, copper, and iron levels in biological samples of normal children and children with night blindness with age groups of 3–7 and 8–12 years,” Biological Trace Element Research, vol. 142, pp. 323–334, 2011.
  43. K. Mochizuki, H. Murase, M. Imose, H. Kawakami, and A. Sawada, “Improvement of scotopic electroretinograms and night blindness with recovery of serum zinc levels,” Japanese Journal of Ophthalmology, vol. 50, no. 6, pp. 532–536, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. A. M. Huber and S. N. Gershoff, “Effects of zinc deficiency on the oxidation of retinol and ethanol in rats,” Journal of Nutrition, vol. 105, no. 11, pp. 1486–1490, 1975. View at Scopus
  45. D. Bok, “Retinal photoreceptor-pigment epithelium interactions,” Investigative Ophthalmology and Visual Science, vol. 26, no. 12, pp. 1659–1694, 1985. View at Scopus
  46. S. Redenti, H. Ripps, and R. L. Chappell, “Zinc release at the synaptic terminals of rod photoreceptors,” Experimental Eye Research, vol. 85, no. 4, pp. 580–584, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. I. Jeru, “The role of zinc in the appearance of cataract,” Oftalmologia, vol. 41, no. 4, pp. 329–332, 1997. View at Scopus
  48. A. Kassoff, J. Kassoff, J. Buehler et al., “A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins c and e and beta carotene for age-related cataract and vision loss: AREDS report no. 9,” Archives of Ophthalmology, vol. 119, no. 10, pp. 1439–1452, 2001.
  49. M. Sato and I. Bremner, “Oxygen free radicals and metallothionein,” Free Radical Biology and Medicine, vol. 14, no. 3, pp. 325–337, 1993. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Tsuruma, H. Shimazaki, Y. Ohno et al., “Metallothionein-iii deficiency exacerbates light-induced retinal degeneration,” Investigative Ophthalmology & Visual Science, vol. 53, pp. 7896–7903, 2012.
  51. J. C. Erie, J. A. Good, J. A. Butz, and J. S. Pulido, “Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration,” American Journal of Ophthalmology, vol. 147, no. 2, pp. 276–282, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. D. Organisciak, P. Wong, C. Rapp, A. Ziesel, R. Rangarajan, and J. Lang, “Light-induced retinal degeneration is prevented by zinc, a component in the age-related eye disease study formulation,” Photochemistry and Photobiology, vol. 88, no. 6, pp. 1396–1407, 2012. View at Publisher · View at Google Scholar
  53. D. J. Tate, D. A. Newsome, and P. D. Oliver, “Metallothionein shows an age-related decrease in human macular retinal pigment epithelium,” Investigative Ophthalmology and Visual Science, vol. 34, no. 7, pp. 2348–2351, 1993. View at Scopus
  54. M. G. Nicolas, K. Fujiki, K. Murayama et al., “Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress,” Experimental Eye Research, vol. 62, no. 4, pp. 399–408, 1996. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Sasaki, H. Shinoda, T. Koto, A. Uchida, K. Tsubota, and Y. Ozawa, “Use of micronutrient supplement for preventing advanced age-related macular degeneration in Japan,” Archives of Ophthalmology, vol. 130, no. 2, pp. 254–255, 2012. View at Publisher · View at Google Scholar
  56. J. H. Olson, J. C. Erie, and S. J. Bakri, “Nutritional supplementation and age-related macular degeneration,” Seminars in Ophthalmology, vol. 26, no. 3, pp. 131–136, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. N. A. Hasan, “Effects of trace elements on albumin and lipoprotein glycation in diabetic retinopathy,” Saudi Medical Journal, vol. 30, no. 10, pp. 1263–1271, 2009. View at Scopus
  58. E. Rudolf, J. Peychl, J. Radocha, and M. Cervinka, “Zinc and its role in the regulation of cell death,” Ceskoslovenska Fysiologie, vol. 50, no. 4, pp. 201–210, 2001. View at Scopus
  59. P. M. Hanna, M. B. Kadiiska, S. J. Jordan, and R. P. Mason, “Role of metallothionein in zinc(II) and chromium(III) mediated tolerance to carbon tetrachloride hepatotoxicity: evidence against a trichloromethyl radical-scavenging mechanism,” Chemical Research in Toxicology, vol. 6, no. 5, pp. 711–717, 1993. View at Scopus
  60. S. A. Moustafa, “Effect of glutathione (GSH) depletion on the serum levels of triiodothyronine (T3), thyroxine (T4), and T3/T4 ratio in allyl alcohol-treated male rats and possible protection with zinc,” International Journal of Toxicology, vol. 20, no. 1, pp. 15–20, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Provinciali, A. Donnini, K. Argentati, G. Di Stasio, B. Bartozzi, and G. Bernardini, “Reactive oxygen species modulate Zn2+-induced apoptosis in cancer cells,” Free Radical Biology and Medicine, vol. 32, no. 5, pp. 431–445, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. J. R. Evans, “Antioxidant vitamin and mineral supplements for age-related macular degeneration.,” Cochrane Database of Systematic Reviews, no. 1, Article ID CD000254, 2002. View at Scopus
  63. V. Duzguner and S. Kaya, “Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits,” Free Radical Biology and Medicine, vol. 42, no. 10, pp. 1481–1486, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Puig and D. J. Thiele, “Molecular mechanisms of copper uptake and distribution,” Current Opinion in Chemical Biology, vol. 6, no. 2, pp. 171–180, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Y. Uriu-Adams and C. L. Keen, “Copper, oxidative stress, and human health,” Molecular Aspects of Medicine, vol. 26, no. 4-5, pp. 268–298, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. N. H. Ansari, W. Zhang, E. Fulep, and A. Mansour, “Prevention of pericyte loss by trolox in diabetic rat retina,” Journal of Toxicology and Environmental Health A, vol. 54, no. 6, pp. 467–475, 1998. View at Scopus
  67. R. A. Kowluru, R. L. Engerman, G. L. Case, and T. S. Kern, “Retinal glutamate in diabetes and effect of antioxidants,” Neurochemistry International, vol. 38, no. 5, pp. 385–390, 2001. View at Publisher · View at Google Scholar · View at Scopus
  68. I. G. Obrosova, A. G. Minchenko, V. Marinescu et al., “Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats,” Diabetologia, vol. 44, no. 9, pp. 1102–1110, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. C. D. Agardh, E. Agardh, B. Hultberg, Y. Qian, and C. G. Östenson, “The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment,” Current Eye Research, vol. 17, no. 3, pp. 251–256, 1998. View at Publisher · View at Google Scholar · View at Scopus
  70. R. A. Kowluru, R. L. Engerman, and T. S. Kern, “Abnormalities of retinal metabolism in diabetes or experimental galactosemia VIII. Prevention by aminoguanidine,” Current Eye Research, vol. 21, no. 4, pp. 814–819, 2000. View at Publisher · View at Google Scholar · View at Scopus
  71. A. C. S. Woollard, Z. A. Bascal, G. R. Armstrong, and S. P. Wolff, “Abnormal redox status without increased lipid peroxidation in sugar cataract,” Diabetes, vol. 39, no. 11, pp. 1347–1352, 1990. View at Scopus
  72. S. A. Moustafa, “Effect of glutathione depletion on carbohydrate metabolism in the rat,” Research Communications in Pharmacology and Toxicology, vol. 3, no. 1-2, pp. 55–64, 1998.
  73. R. I. Fink, T. Huecksteadt, and Z. Karaoghlanian, “The effects of aging on glucose metabolism in adipocytes from Fischer rats,” Endocrinology, vol. 118, no. 3, pp. 1139–1147, 1986. View at Scopus
  74. S. A. Moustafa, J. E. Webster, and F. E. Mattar, “Effects of aging and antioxidants on glucose transport in rat adipocytes,” Gerontology, vol. 41, no. 6, pp. 301–307, 1995. View at Scopus
  75. A. Kowald and T. B. L. Kirkwood, “Towards a new theory of aging and the protein error theory,” Journal of Theoretical Biology, vol. 168, pp. 75–94, 1994.
  76. J. P. Thomas, G. J. Bachowski, and A. W. Girotti, “Inhibition of cell membrane lipid peroxidation by cadmium- and zinc-metallothioneins,” Biochimica et Biophysica Acta, vol. 884, no. 3, pp. 448–461, 1986. View at Scopus
  77. Z. E. Suntres and E. M. K. Lui, “Biochemical mechanism of metallothionein-carbon tetrachloride interaction in vitro,” Biochemical Pharmacology, vol. 39, no. 5, pp. 833–840, 1990. View at Publisher · View at Google Scholar · View at Scopus
  78. P. J. Thornalley and M. Vasak, “Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals,” Biochimica et Biophysica Acta, vol. 827, no. 1, pp. 36–44, 1985. View at Publisher · View at Google Scholar · View at Scopus
  79. C. M. St Croix, K. J. Wasserloos, K. E. Dineley, I. J. Reynolds, E. S. Levitan, and B. R. Pitt, “Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein,” American Journal of Physiology, vol. 282, no. 2, pp. L185–L192, 2002. View at Scopus
  80. Y. Zhang, W. Zhao, H. J. Zhang, F. E. Domann, and L. W. Oberley, “Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth,” Cancer Research, vol. 62, no. 4, pp. 1205–1212, 2002. View at Scopus
  81. S. I. Yamagishi, S. Amano, Y. Inagaki et al., “Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes,” Biochemical and Biophysical Research Communications, vol. 290, no. 3, pp. 973–978, 2002. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Kim, K. M. Kim, C.-S. Kim et al., “Puerarin inhibits the retinal pericyte apoptosis induced by advanced glycation end products in vitro and in vivo by inhibiting NADPH oxidase-related oxidative stress,” Free Radical Biology and Medicine, vol. 53, no. 2, pp. 357–365, 2012. View at Publisher · View at Google Scholar
  83. A. C. Clermont, L. P. Aiello, F. Mori, L. M. Aiello, and S. E. Bursell, “Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo: a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy,” American Journal of Ophthalmology, vol. 124, no. 4, pp. 433–446, 1997. View at Scopus
  84. X. Wang, G. Wang, and Y. Wang, “Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy,” American Journal of Ophthalmology, vol. 148, no. 6, pp. 883–889, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. A. P. Adamis, J. W. Miller, M. T. Bernal et al., “Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy,” American Journal of Ophthalmology, vol. 118, no. 4, pp. 445–450, 1994. View at Scopus
  86. C. M. Andreoli and J. W. Miller, “Anti-vascular endothelial growth factor therapy for ocular neovascular disease,” Current Opinion in Ophthalmology, vol. 18, no. 6, pp. 502–508, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. R. G. Uzzo, P. L. Crispen, K. Golovine, P. Makhov, E. M. Horwitz, and V. M. Kolenko, “Diverse effects of zinc on NF-κB and AP-1 transcription factors: implications for prostate cancer progression,” Carcinogenesis, vol. 27, no. 10, pp. 1980–1990, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. M. DeNiro and F. A. Al-Mohanna, “Zinc transporter 8 (znt8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy,” PLoS ONE, vol. 7, no. 11, Article ID e50360, 2012. View at Publisher · View at Google Scholar
  89. T. Adachi, M. Teramachi, H. Yasuda, T. Kamiya, and H. Hara, “Contribution of p38 MAPK, NF-κB and glucocorticoid signaling pathways to ER stress-induced increase in retinal endothelial permeability,” Archives of Biochemistry and Biophysics, vol. 520, no. 1, pp. 30–35, 2012. View at Publisher · View at Google Scholar
  90. Y. Zhao, Y. Tan, J. Dai et al., “Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice,” Toxicology Letters, vol. 200, no. 1-2, pp. 100–106, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. L. Scheppke, E. Aguilar, R. F. Gariano et al., “Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits,” Journal of Clinical Investigation, vol. 118, no. 6, pp. 2337–2346, 2008. View at Publisher · View at Google Scholar · View at Scopus