PPAR Research
Volume 2008 (2008), Article ID 389507, 11 pages
doi:10.1155/2008/389507
Review Article

Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration

Alexandra A. Herzlich, Jingsheng Tuo, and Chi-Chao Chan

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda 20892-1857, MD, USA

Received 2 October 2007; Accepted 14 November 2007

Academic Editor: R. S. Chuck

Copyright © 2008 Alexandra A. Herzlich 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. D. S. Friedman, B. J. O'Colmain, and B. Muñoz, et al., “Prevalence of age-related macular degeneration in the United States,” Archives of Ophthalmology, vol. 122, no. 4, pp. 564–572, 2004. View at Publisher · View at Google Scholar · View at PubMed
  2. S. Kersten, B. Desvergne, and W. Wahli, “Roles of PPARS in health and disease,” Nature, vol. 405, no. 6785, pp. 421–424, 2000. View at Publisher · View at Google Scholar · View at PubMed
  3. L. S. Forno, “Neuropathology of Parkinson's disease,” Journal of Neuropathology and Experimental Neurology, vol. 55, no. 3, pp. 259–272, 1996. View at Publisher · View at Google Scholar
  4. D. P. Perl, “Neuropathology of Alzheimer's disease and related disorders,” Neurologic Clinics, vol. 18, no. 4, pp. 847–864, 2000. View at Publisher · View at Google Scholar
  5. E. Friedman, “A hemodynamic model of the pathogenesis of age-related macular degeneration,” American Journal of Ophthalmology, vol. 124, no. 5, pp. 677–682, 1997.
  6. P. T. V. M. De Jong, “Age-related macular degeneration,” New England Journal of Medicine, vol. 355, no. 14, pp. 1474–1485, 2006. View at Publisher · View at Google Scholar · View at PubMed
  7. S. H. Sarks, J. J. Arnold, M. C. Killingsworth, and J. P. Sarks, “Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study,” British Journal of Ophthalmology, vol. 83, no. 3, pp. 358–368, 1999. View at Publisher · View at Google Scholar
  8. S. Beatty, H.-H. Koh, M. Phil, D. Henson, and M. Boulton, “The role of oxidative stress in the pathogenesis of age-related macular degeneration,” Survey of Ophthalmology, vol. 45, no. 2, pp. 115–134, 2000. View at Publisher · View at Google Scholar
  9. J. P. SanGiovanni and E. Y. Chew, “The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina,” Progress in Retinal and Eye Research, vol. 24, no. 1, pp. 87–138, 2005. View at Publisher · View at Google Scholar · View at PubMed
  10. B. S. Winkler, M. E. Boulton, J. D. Gottsch, and P. Sternberg, “Oxidative damage and age-related macular degeneration,” Molecular Vision, vol. 5, p. 32, 1999.
  11. W. G. Christen, R. J. Glynn, J. E. Manson, U. A. Ajani, and J. E. Buring, “A prospective study of cigarette smoking and risk of age-related macular degeneration in men,” Journal of the American Medical Association, vol. 276, no. 14, pp. 1147–1151, 1996. View at Publisher · View at Google Scholar
  12. J. M. Seddon, W. C. Willett, F. E. Speizer, and S. E. Hankinson, “A prospective study of cigarette smoking and age-related macular degeneration in women,” Journal of the American Medical Association, vol. 276, no. 14, pp. 1141–1146, 1996. View at Publisher · View at Google Scholar
  13. J. M. Seddon, U. A. Ajani, and B. D. Mitchell, “Familial aggregation of age-related maculopathy,” American Journal of Ophthalmology, vol. 123, no. 2, pp. 199–206, 1997.
  14. J. M. Seddon, S. George, and B. Rosner, “Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US twin study of age-related macular degeneration,” Archives of Ophthalmology, vol. 124, no. 7, pp. 995–1001, 2006. View at Publisher · View at Google Scholar · View at PubMed
  15. J. M. Seddon, S. George, B. Rosner, and M. L. Klein, “CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration,” Human Heredity, vol. 61, no. 3, pp. 157–165, 2006. View at Publisher · View at Google Scholar · View at PubMed
  16. J. Tuo, C. M. Bojanowski, and C.-C. Chan, “Genetic factors of age-related macular degeneration,” Progress in Retinal and Eye Research, vol. 23, no. 2, pp. 229–249, 2004. View at Publisher · View at Google Scholar · View at PubMed
  17. J. J. Wang, R. J. Ross, and J. Tuo, et al., “The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration: a population-based case-control study,” to appear in Ophthalmology.
  18. R. J. Klein, C. Zeiss, and E. Y. Chew, et al., “Complement factor H polymorphism in age-related macular degeneration,” Science, vol. 308, no. 5720, pp. 385–389, 2005. View at Publisher · View at Google Scholar · View at PubMed
  19. A. O. Edwards, R. Ritter III, K. J. Abel, A. Manning, C. Panhuysen, and L. A. Farrer, “Complement factor H polymorphism and age-related macular degeneration,” Science, vol. 308, no. 5720, pp. 421–424, 2005. View at Publisher · View at Google Scholar · View at PubMed
  20. J. L. Haines, M. A. Hauser, and S. Schmidt, et al., “Complement factor H variant increases the risk of age-related macular degeneration,” Science, vol. 308, no. 5720, pp. 419–421, 2005. View at Publisher · View at Google Scholar · View at PubMed
  21. G. S. Hageman, D. H. Anderson, and L. V. Johnson, et al., “From The Cover GENETICS: a common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 20, pp. 7227–7232, 2005. View at Publisher · View at Google Scholar · View at PubMed
  22. Y. P. Conley, A. Thalamuthu, and J. Jakobsdottir, et al., “Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy,” Human Molecular Genetics, vol. 14, no. 14, pp. 1991–2002, 2005. View at Publisher · View at Google Scholar · View at PubMed
  23. E. H. Souied, N. Leveziel, and F. Richard, et al., “Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population,” Molecular Vision, vol. 11, pp. 1135–1140, 2005.
  24. R. J. Ross, C. M. Bojanowski, and J. J. Wang, et al., “The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples,” Investigative Ophthalmology and Visual Science, vol. 48, no. 3, pp. 1128–1132, 2007. View at Publisher · View at Google Scholar · View at PubMed
  25. J. Jakobsdottir, Y. P. Conley, D. E. Weeks, T. S. Mah, R. E. Ferrell, and M. B. Gorin, “Susceptibility genes for age-related maculopathy on chromosome 10q26,” American Journal of Human Genetics, vol. 77, no. 3, pp. 389–407, 2005. View at Publisher · View at Google Scholar · View at PubMed
  26. A. Rivera, S. A. Fisher, and L. G. Fritsche, et al., “Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk,” Human Molecular Genetics, vol. 14, no. 21, pp. 3227–3236, 2005. View at Publisher · View at Google Scholar · View at PubMed
  27. S. Schmidt, M. A. Hauser, and W. K. Scott, et al., “Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration,” American Journal of Human Genetics, vol. 78, no. 5, pp. 852–864, 2006. View at Publisher · View at Google Scholar · View at PubMed
  28. Z. Yang, N. J. Camp, and H. Sun, et al., “A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration,” Science, vol. 314, no. 5801, pp. 992–993, 2006. View at Publisher · View at Google Scholar · View at PubMed
  29. A. DeWan, M. Liu, and S. Hartman, et al., “HTRA1 promoter polymorphism in wet age-related macular degeneration,” Science, vol. 314, no. 5801, pp. 989–992, 2006. View at Publisher · View at Google Scholar · View at PubMed
  30. A. E. Hughes, N. Orr, H. Esfandiary, M. Diaz-Torres, T. Goodship, and U. Chakravarthy, “A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration,” Nature Genetics, vol. 38, no. 10, pp. 1173–1177, 2006. View at Publisher · View at Google Scholar · View at PubMed
  31. F. Simonelli, M. Margaglione, and F. Testa, et al., “Apolipoprotein E polymorphisms in age-related macular degeneration in an Italian population,” Ophthalmic Research, vol. 33, no. 6, pp. 325–328, 2001. View at Publisher · View at Google Scholar
  32. J. D. Smith, “Apolipoprotein E4: an allele associated with many diseases,” Annals of Medicine, vol. 32, no. 2, pp. 118–127, 2000. View at Publisher · View at Google Scholar
  33. S. Al-Shammri, H. Fatania, R. Al-Radwan, and A. O. Akanji, “The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects,” Clinica Chimica Acta, vol. 351, no. 1-2, pp. 203–207, 2005. View at Publisher · View at Google Scholar · View at PubMed
  34. S. Schmidt, J. L. Haines, and E. A. Postel, et al., “Joint effects of smoking history and APOE genotypes in age-related macular degeneration,” Molecular Vision, vol. 11, pp. 941–949, 2005.
  35. J. L. Haines, N. Schnetz-Boutaud, and S. Schmidt, et al., “Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6,” Investigative Ophthalmology and Visual Science, vol. 47, no. 1, pp. 329–335, 2006. View at Publisher · View at Google Scholar · View at PubMed
  36. A. J. Churchill, J. G. Carter, and H. C. Lovell, et al., “VEGF polymorphisms are associated with neovascular age-related macular degeneration,” Human Molecular Genetics, vol. 15, no. 19, pp. 2955–2961, 2006. View at Publisher · View at Google Scholar · View at PubMed
  37. N. Fiotti, M. Pedio, and M. B. Parodi, et al., “MMP-9 microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration,” Genetics in Medicine, vol. 7, no. 4, pp. 272–277, 2005. View at Publisher · View at Google Scholar
  38. A. Kassoff, J. Kassoff, and J. Buehler, et al., “A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8,” Archives of Ophthalmology, vol. 119, no. 10, pp. 1417–1436, 2001.
  39. J. M. Seddon, J. Cote, and B. Rosner, “Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake,” Archives of Ophthalmology, vol. 121, no. 12, pp. 1728–1737, 2003. View at Publisher · View at Google Scholar · View at PubMed
  40. C. V. Rojas, R. S. Greiner, L. C. Fuenzalida, J. I. Martínez, N. Salem Jr., and R. Uauy, “Long-term n-3 FA deficiency modifies peroxisome proliferator-activated receptor β mRNA abundance in rat ocular tissues,” Lipids, vol. 37, no. 4, pp. 367–374, 2002. View at Publisher · View at Google Scholar
  41. J. P. SanGiovanni, E. Y. Chew, and T. E. Clemons, et al., “The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS report No. 22,” Archives of Ophthalmology, vol. 125, no. 9, pp. 1225–1232, 2007. View at Publisher · View at Google Scholar · View at PubMed
  42. J. Kanki and S. Milewski, “Acquired macular disorders: age-related macular degeneration,” Diseases of the Macula, vol. 23, no. 1, pp. 57–59, 2002.
  43. D. A. Quillen, “Common causes of vision loss in elderly patients,” American Family Physician, vol. 60, no. 1, pp. 99–108, 1999.
  44. M. G. Maguire, S. B. Bressler, and N. M. Bresskr, et al., “Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration,” Archives of Ophthalmology, vol. 115, no. 6, pp. 741–747, 1997.
  45. D. H. Anderson, S. Ozaki, and M. Nealon, et al., “Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation,” American Journal of Ophthalmology, vol. 131, no. 6, pp. 767–781, 2001. View at Publisher · View at Google Scholar
  46. A. Abdelsalam, L. Del Priore, and M. A. Zarbin, “Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression,” Survey of Ophthalmology, vol. 44, no. 1, pp. 1–29, 1999. View at Publisher · View at Google Scholar
  47. T. Wong, U. Chakravarthy, and R. Klein, et al., “The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis,” to appear in Ophthalmology.
  48. M. Lu and A. P. Adamis, “Molecular biology of choroidal neovascularization,” Ophthalmology Clinics of North America, vol. 19, no. 3, pp. 323–334, 2006. View at Publisher · View at Google Scholar · View at PubMed
  49. P. A. D'Amore, “Mechanisms of retinal and choroidal neovascularization,” Investigative Ophthalmology and Visual Science, vol. 35, no. 12, pp. 3974–3979, 1994.
  50. E. C. Hirsch, T. Breidert, E. Rousselet, S. Hunot, A. Hartmann, and P. P. Michel, “The role of glial reaction and inflammation in Parkinson's disease,” Annals of the New York Academy of Sciences, vol. 991, no. 1, pp. 214–228, 2003.
  51. W. R. Green, “Histopathology of age-related macular degeneration,” Molecular Vision, vol. 5, no. 1, pp. 27–36, 1999.
  52. M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998. View at Publisher · View at Google Scholar · View at PubMed
  53. T. Murata, S. He, and M. Hangai, et al., “Peroxisome proliferator-activated receptor-γ ligands inhibit choroidal neovascularization,” Investigative Ophthalmology and Visual Science, vol. 41, no. 8, pp. 2309–2317, 2000.
  54. J. Auwerx, “PPARγ, the ultimate thrifty gene,” Diabetologia, vol. 42, no. 9, pp. 1033–1049, 1999. View at Publisher · View at Google Scholar
  55. A. B. Reiss and M. E. Vagell, “PPARγ activity in the vessel wall: anti-atherogenic properties,” Current Medicinal Chemistry, vol. 13, no. 26, pp. 3227–3238, 2006.
  56. S. A. Kliewer, J. M. Lenhard, T. M. Willson, I. Patel, D. C. Morris, and J. M. Lehmann, “A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation,” Cell, vol. 83, no. 5, pp. 813–819, 1995. View at Publisher · View at Google Scholar
  57. S. A. Kliewer, S. S. Sundseth, and S. A. Jones, et al., “Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4318–4323, 1997. View at Publisher · View at Google Scholar
  58. J.-B. Pialat, T.-H. Cho, and O. Beuf, et al., “MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated receptor (PPAR)-deficient mice,” NMR in Biomedicine, vol. 20, no. 3, pp. 335–342, 2007. View at Publisher · View at Google Scholar · View at PubMed
  59. R. Bordet, P. Gelé, P. Duriez, and J.-C. Fruchart, “PPARs: a new target for neuroprotection,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 77, no. 3, pp. 285–286, 2006. View at Publisher · View at Google Scholar · View at PubMed
  60. S. Green, “PPAR: a mediator of peroxisome proliferator action,” Mutation Research, vol. 333, no. 1-2, pp. 101–109, 1995. View at Publisher · View at Google Scholar
  61. X. Xin, S. Yang, J. Kowalski, and M. E. Gerritsen, “Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo,” Journal of Biological Chemistry, vol. 274, no. 13, pp. 9116–9121, 1999. View at Publisher · View at Google Scholar
  62. G. D. Girnun, F. E. Domann, S. A. Moore, and M. E. C. Robbins, “Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter,” Molecular Endocrinology, vol. 16, no. 12, pp. 2793–2801, 2002. View at Publisher · View at Google Scholar
  63. X. Zhao, Y. Zhang, R. Strong, J. C. Grotta, and J. Aronowski, “15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-γ, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats,” Journal of Cerebral Blood Flow and Metabolism, vol. 26, no. 6, pp. 811–820, 2006. View at Publisher · View at Google Scholar · View at PubMed
  64. M. Schrader and H. D. Fahimi, “Peroxisomes and oxidative stress,” Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1763, no. 12, pp. 1755–1766, 2006. View at Publisher · View at Google Scholar · View at PubMed
  65. S. J. Fliesler and R. E. Anderson, “Chemistry and metabolism of lipids in the vertebrate retina,” Progress in Lipid Research, vol. 22, no. 2, pp. 79–131, 1983. View at Publisher · View at Google Scholar
  66. J. R. Sparrow and M. Boulton, “RPE lipofuscin and its role in retinal pathobiology,” Experimental Eye Research, vol. 80, no. 5, pp. 595–606, 2005. View at Publisher · View at Google Scholar · View at PubMed
  67. E. R. Gaillard, S. J. Atherton, G. Eldred, and J. Dillon, “Photophysical studies on human retinal lipofuscin,” Photochemistry and Photobiology, vol. 61, no. 5, pp. 448–453, 1995. View at Publisher · View at Google Scholar
  68. M. A. Zarbin, “Current concepts in the pathogenesis of age-related macular degeneration,” Archives of Ophthalmology, vol. 122, no. 4, pp. 598–614, 2004. View at Publisher · View at Google Scholar · View at PubMed
  69. R. Klein, B. E. K. Klein, S. C. Tomany, and S. E. Moss, “Ten-year incidence of age-related maculopathy and smoking and drinking: the Beaver Dam Eye Study,” American Journal of Epidemiology, vol. 156, no. 7, pp. 589–598, 2002. View at Publisher · View at Google Scholar
  70. Q. Ding, E. Dimayuga, and J. N. Keller, “Oxidative damage, protein synthesis, and protein degradation in Alzheimer's disease,” Current Alzheimer Research, vol. 4, no. 1, pp. 73–79, 2007. View at Publisher · View at Google Scholar
  71. H. Sun, P. M. Smallwood, and J. Nathans, “Biochemical defects in ABCR protein variants associated with human retinopathies,” Nature Genetics, vol. 26, no. 2, pp. 242–246, 2000. View at Publisher · View at Google Scholar · View at PubMed
  72. Z. S. Tan, A. S. Beiser, and R. S. Vasan, et al., “Inflammatory markers and the risk of Alzheimer disease: the Framingham study,” Neurology, vol. 68, no. 22, pp. 1902–1908, 2007. View at Publisher · View at Google Scholar · View at PubMed
  73. V. M. Victor and M. Rocha, “Targeting antioxidants to mitochondria: a potential new therapeutic strategy for cardiovascular diseases,” Current Pharmaceutical Design, vol. 13, no. 8, pp. 845–863, 2007. View at Publisher · View at Google Scholar
  74. R. W. Young, “Solar radiation and age-related macular degeneration,” Survey of Ophthalmology, vol. 32, no. 4, pp. 252–269, 1988. View at Publisher · View at Google Scholar
  75. J. Tuo, C. M. Bojanowski, and M. Zhou, et al., “Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration,” Investigative Ophthalmology and Visual Science, vol. 48, no. 8, pp. 3827–3836, 2007. View at Publisher · View at Google Scholar · View at PubMed
  76. K. Daub, S. Lindemann, and H. Langer, et al., “The evil in atherosclerosis: adherent platelets induce foam cell formation,” Seminars in Thrombosis and Hemostasis, vol. 33, no. 2, pp. 173–178, 2007. View at Publisher · View at Google Scholar · View at PubMed
  77. R. Dirkx, I. Vanhorebeek, and K. Martens, et al., “Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities,” Hepatology, vol. 41, no. 4, pp. 868–878, 2005. View at Publisher · View at Google Scholar · View at PubMed
  78. S. M. Weber, K. T. Chambers, K. G. Bensch, A. L. Scarim, and J. A. Corbett, “PPARγ ligands induce ER stress in pancreatic β-cells: ER stress activation results in attenuation of cytokine signaling,” American Journal of Physiology - Endocrinology and Metabolism, vol. 287, no. 6 50-6, pp. E1171–E1177, 2004. View at Publisher · View at Google Scholar · View at PubMed
  79. G. S. Hageman, P. J. Luthert, N. H. Victor Chong, L. V. Johnson, D. H. Anderson, and R. F. Mullins, “An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration,” Progress in Retinal and Eye Research, vol. 20, no. 6, pp. 705–732, 2001. View at Publisher · View at Google Scholar
  80. D. M. Moshfeghi and M. S. Blumenkranz, “Role of genetic factors and inflammation in age-related macular degeneration,” Retina, vol. 27, no. 3, pp. 269–275, 2007. View at Publisher · View at Google Scholar · View at PubMed
  81. R. F. Mullins, S. R. Russell, D. H. Anderson, and G. S. Hageman, “Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease,” FASEB Journal, vol. 14, no. 7, pp. 835–846, 2000.
  82. L. A. Donoso, D. Kim, A. Frost, A. Callahan, and G. Hageman, “The role of inflammation in the pathogenesis of age-related macular degeneration,” Survey of Ophthalmology, vol. 51, no. 2, pp. 137–152, 2006. View at Publisher · View at Google Scholar · View at PubMed
  83. D. Colville, R. Guyner, R. Sinclair, and J. Savige, “Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type 2 (“dense deposit disease”),” American Journal of Kidney Diseases, vol. 42, no. 2, pp. E2–E5, 2003. View at Publisher · View at Google Scholar
  84. S. J. Huang, D. L. L. Costa, N. E. Gross, and L. A. Yannuzzi, “Peripheral drusen in membranoproliferative glomerulonephritis type II,” Retina, vol. 23, no. 3, pp. 429–431, 2003. View at Publisher · View at Google Scholar
  85. M. A. Grassi, J. C. Folk, T. E. Scheetz, C. M. Taylor, V. C. Sheffield, and E. M. Stone, “Complement factor H polymorphism p.Tyr402His and cuticular drusen,” Archives of Ophthalmology, vol. 125, no. 1, pp. 93–97, 2007. View at Publisher · View at Google Scholar · View at PubMed
  86. D. H. Anderson, R. F. Mullins, G. S. Hageman, and L. V. Johnson, “A role for local inflammation in the formation of drusen in the aging eye,” American Journal of Ophthalmology, vol. 134, no. 3, pp. 411–431, 2002. View at Publisher · View at Google Scholar
  87. L. V. Johnson, W. P. Leitner, M. K. Staples, and D. H. Anderson, “Complement activation and inflammatory processes in drusen formation and age related macular degeneration,” Experimental Eye Research, vol. 73, no. 6, pp. 887–896, 2001. View at Publisher · View at Google Scholar · View at PubMed
  88. P. L. McGeer and E. G. McGeer, “Inflammation and the degenerative diseases of aging,” Annals of the New York Academy of Sciences, vol. 1035, pp. 104–116, 2004. View at Publisher · View at Google Scholar · View at PubMed
  89. Z. S. Galis and J. J. Khatri, “Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly,” Circulation Research, vol. 90, no. 3, pp. 251–262, 2002.
  90. O. Tatar, A. Adam, and K. Shinoda, et al., “Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy,” British Journal of Ophthalmology, vol. 91, no. 9, pp. 1183–1189, 2007. View at Publisher · View at Google Scholar · View at PubMed
  91. G. S. Hageman, D. H. Anderson, and L. V. Johnson, et al., “A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 20, pp. 7227–7232, 2005. View at Publisher · View at Google Scholar · View at PubMed
  92. R. J. Ross, V Verma, KI Rosenberg, C.-C. Chan, and J. Tuo, “Genetic markers and biomarkers for age-related macular degeneration,” Expert Review of Ophthalmology, vol. 2, no. 3, pp. 443–457, 2007. View at Publisher · View at Google Scholar · View at PubMed
  93. G. S. Hageman, P. J. Luthert, N. H. Victor Chong, L. V. Johnson, D. H. Anderson, and R. F. Mullins, “An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration,” Progress in Retinal and Eye Research, vol. 20, no. 6, pp. 705–732, 2001. View at Publisher · View at Google Scholar
  94. J. M. Seddon, P. J. Francis, S. George, D. W. Schultz, B. Rosner, and M. L. Klein, “Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration,” Journal of the American Medical Association, vol. 297, no. 16, pp. 1793–1800, 2007. View at Publisher · View at Google Scholar · View at PubMed
  95. N. Ferrara and R. S. Kerbel, “Angiogenesis as a therapeutic target,” Nature, vol. 438, no. 7070, pp. 967–974, 2005. View at Publisher · View at Google Scholar · View at PubMed
  96. S. A. Vinores, W.-H. Xiao, and S. Aslam, et al., “Implication of the hypoxia response element of the Vegf promoter in mouse models of retinal and choroidal neovascularization, but not retinal vascular development,” Journal of Cellular Physiology, vol. 206, no. 3, pp. 749–758, 2006. View at Publisher · View at Google Scholar · View at PubMed
  97. T. Mustonen and K. Alitalo, “Endothelial receptor tyrosine kinases involved in angiogenesis,” Journal of Cell Biology, vol. 129, no. 4, pp. 895–898, 1995. View at Publisher · View at Google Scholar
  98. J. Kroll and J. Waltenberger, “The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells,” Journal of Biological Chemistry, vol. 272, no. 51, pp. 32521–32527, 1997. View at Publisher · View at Google Scholar
  99. A. Parenti, L. Morbidelli, and X.-L. Cui, et al., “Nitric oxide is an upstream signal of vascular endothelial growth factor-induced extracellular signal-regulated kinase( 1/4 ) activation in postcapillary endothelium,” Journal of Biological Chemistry, vol. 273, no. 7, pp. 4220–4226, 1998. View at Publisher · View at Google Scholar
  100. U. M. Schmidt-Erfurth and C. Pruente, “Management of neovascular age-related macular degeneration,” Progress in Retinal and Eye Research, vol. 26, no. 4, pp. 437–451, 2007. View at Publisher · View at Google Scholar · View at PubMed
  101. P. J. Rosenfeld, D. M. Brown, and J. S. Heier, et al., “Ranibizumab for neovascular age-related macular degeneration,” New England Journal of Medicine, vol. 355, no. 14, pp. 1419–1431, 2006. View at Publisher · View at Google Scholar · View at PubMed
  102. E. S. Gragoudas, A. P. Adamis, E. T. Cunningham Jr., M. Feinsod, and D. R. Guyer, “Pegaptanib for neovascular age-related macular degeneration,” New England Journal of Medicine, vol. 351, no. 27, pp. 2805–2816, 2004. View at Publisher · View at Google Scholar · View at PubMed
  103. M. Kliffen, H. S. Sharma, C. M. Mooy, S. Kerkvliet, and P. T. V. M. De Jong, “Increased expression of angiogenic growth factors in age-related maculopathy,” British Journal of Ophthalmology, vol. 81, no. 2, pp. 154–162, 1997. View at Publisher · View at Google Scholar
  104. W. Y. Shen, M. J. T. Yu, C. J. Barry, I. J. Constable, and P. E. Rakoczy, “Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat,” British Journal of Ophthalmology, vol. 82, no. 9, pp. 1063–1071, 1998. View at Publisher · View at Google Scholar
  105. A. R. Folgueras, A. M. Pendás, L. M. Sánchez, and C. López-Otín, “Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies,” International Journal of Developmental Biology, vol. 48, no. 5-6, pp. 411–424, 2004. View at Publisher · View at Google Scholar · View at PubMed
  106. N. Marx, J. Froehlich, and L. Siam, et al., “Antidiabetic PPARγ-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 2, pp. 283–288, 2003. View at Publisher · View at Google Scholar
  107. A. R. Collins, W. P. Meehan, and U. Kintscher, et al., “Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 3, pp. 365–371, 2001.
  108. K. Y. Chau and N. Patel, “Plasma levels of matrix metalloproteinase - 2 and -9 in age-related macular degeneration,” to appear in Eye.
  109. L. Guo, A. A. Hussain, G. A. Limb, and J. Marshall, “Age-dependent variation in metalloproteinase activity of isolated human Bruch's membrane and choroid,” Investigative Ophthalmology and Visual Science, vol. 40, no. 11, pp. 2676–2682, 1999.
  110. V. Lambert, B. Wielockx, and C. Munaut, et al., “MMP-2 and MMP-9 synergize in promoting choroidal neovascularization,” FASEB Journal, vol. 17, no. 15, pp. 2290–2292, 2003. View at Publisher · View at Google Scholar · View at PubMed
  111. N. G. Bazan, “Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors,” Trends in Neurosciences, vol. 29, no. 5, pp. 263–271, 2006. View at Publisher · View at Google Scholar · View at PubMed
  112. N. Marx, T. Bourcier, G. K. Sukhova, P. Libby, and J. Plutzky, “PPARγ activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARγ as a potential mediator in vascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 3, pp. 546–551, 1999.
  113. M. R. Gralinski, P. E. Rowse, and M. A. Breider, “Effects of troglitazone and pioglitazone on cytokine-mediated endothelial cell proliferation in vitro,” Journal of Cardiovascular Pharmacology, vol. 31, no. 6, pp. 909–913, 1998. View at Publisher · View at Google Scholar
  114. P. Delerive, F. Martin-Nizard, and G. Chinetti, et al., “Peroxisome proliferator-activated receptor activators inhibit thrombin- induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway,” Circulation Research, vol. 85, no. 5, pp. 394–402, 1999.
  115. R. M. Touyz and E. L. Schiffrin, “Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications,” Vascular Pharmacology, vol. 45, no. 1, pp. 19–28, 2006. View at Publisher · View at Google Scholar · View at PubMed
  116. N. Marx, G. Sukhova, C. Murphy, P. Libby, and J. Plutzky, “Macrophages in human atheroma contain PPARγ: differentiation-dependent peroxisomal proliferator-activated receptor γ (PPARγ) expression and reduction of MMP-9 activity through PPARγ activation in mononuclear phagocytes in vitro,” American Journal of Pathology, vol. 153, no. 1, pp. 17–23, 1998.
  117. K.-J. Lee, H.-A. Kim, and P.-H. Kim, et al., “Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-γ,” Experimental and Molecular Medicine, vol. 36, no. 6, pp. 534–544, 2004.
  118. S. Qin, A. P. McLaughlin, and G. W. De Vries, “Protection of RPE cells from oxidative injury by 15-deoxy-Δ12,14-prostaglandin J2 by augmenting GSH and activating MAPK,” Investigative Ophthalmology and Visual Science, vol. 47, no. 11, pp. 5098–5105, 2006. View at Publisher · View at Google Scholar · View at PubMed