Inflammation and the pathogenesis of age-related macular degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. Many changes occur in various areas of the eye as it ages. These include choroidal thinning, thickening of Bruch's membrane and drusen formation. Each of these is associated with the onset of AMD. Methods: Recent findings on how those changes contribute to the pathogenesis of AMD with a focus on inflammation are examined. Results: There is evidence suggesting that all changes identified so far as being involved in the pathogenesis of AMD are not able to cause AMD alone. Instead, susceptibility genes, and in particular a coding variant of a gene on chromosome 1 result in dysfunction of the immune system. This leads to an inappropriate inflammatory response, which then sets the stage for AMD onset. Conclusions: It is now well-known that AMD is a multi-factorial disease, with environmental causes and genetics all playing a role.

[1]  Hermann b. Pagenstecher,et al.  Atlas der pathologischen Anatomie des Augapfels , 2011 .

[2]  E. Souied,et al.  [Epidemiology of age related macular degeneration]. , 2009, Journal francais d'ophtalmologie.

[3]  B. Klein,et al.  Combined effects of complement factor H genotypes, fish consumption, and inflammatory markers on long-term risk for age-related macular degeneration in a cohort. , 2008, American journal of epidemiology.

[4]  R. Klein,et al.  Inflammation, complement factor h, and age-related macular degeneration: the Multi-ethnic Study of Atherosclerosis. , 2008, Ophthalmology.

[5]  K. Tsubota,et al.  Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. , 2008, Investigative ophthalmology & visual science.

[6]  P. Mitchell,et al.  The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration. A population-based case-control study. , 2008, Ophthalmology.

[7]  Joe G Hollyfield,et al.  Oxidative damage–induced inflammation initiates age-related macular degeneration , 2008, Nature Medicine.

[8]  P. Debré,et al.  CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. , 2007, The Journal of clinical investigation.

[9]  A. Hofman,et al.  C-reactive protein level and risk of aging macula disorder: The Rotterdam Study. , 2007, Archives of ophthalmology.

[10]  Lois E. H. Smith,et al.  Overstaying their welcome: defective CX3CR1 microglia eyed in macular degeneration. , 2007, The Journal of clinical investigation.

[11]  H. Hense,et al.  Modeling smoking history: a comparison of different approaches in the MARS study on age-related maculopathy. , 2007, Annals of epidemiology.

[12]  E. B. Rodrigues,et al.  Inflammation in Dry Age-Related Macular Degeneration , 2007, Ophthalmologica.

[13]  R. Apte,et al.  Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration , 2006, PLoS medicine.

[14]  Usha Chakravarthy,et al.  Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). , 2006, Archives of ophthalmology.

[15]  Alston Callahan,et al.  The role of inflammation in the pathogenesis of age-related macular degeneration. , 2006, Survey of ophthalmology.

[16]  P. Mcgeer,et al.  Inflammation, the complement system and the diseases of aging , 2005, Neurobiology of Aging.

[17]  M. Tso,et al.  Activation of microglia and chemokines in light-induced retinal degeneration. , 2005, Molecular vision.

[18]  P. Mitchell,et al.  Smoking and age-related macular degeneration: a review of association , 2005, Eye.

[19]  R. T. Smith,et al.  A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Ning Zhang,et al.  Neutrophils promote experimental choroidal neovascularization. , 2005, Molecular vision.

[21]  J. Gilbert,et al.  Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration , 2005, Science.

[22]  A. Edwards,et al.  Complement Factor H Polymorphism and Age-Related Macular Degeneration , 2005, Science.

[23]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[24]  S. Daiger,et al.  Was the Human Genome Project Worth the Effort? , 2005, Science.

[25]  B. Munoz,et al.  Racial variations in causes of vision loss in nursing homes: The Salisbury Eye Evaluation in Nursing Home Groups (SEEING) Study. , 2004, Archives of ophthalmology.

[26]  R. Klein,et al.  Causes and prevalence of visual impairment among adults in the United States. , 2004, Archives of ophthalmology.

[27]  Benita J. O’Colmain,et al.  Prevalence of age-related macular degeneration in the United States. , 2004, Archives of ophthalmology.

[28]  T. Peto,et al.  The epidemiology of age-related macular degeneration. , 2004, American journal of ophthalmology.

[29]  Eiji Sakurai,et al.  An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice , 2003, Nature Medicine.

[30]  J. Ambati,et al.  Macrophage depletion inhibits experimental choroidal neovascularization. , 2003, Investigative ophthalmology & visual science.

[31]  K. Csaky,et al.  Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. , 2003, Investigative ophthalmology & visual science.

[32]  Robert F. Mullins,et al.  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 , 2001, Progress in Retinal and Eye Research.

[33]  J. Neitz,et al.  Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation. , 2001, American journal of ophthalmology.

[34]  M. Gillies,et al.  Immunological and Aetiological Aspects of Macular Degeneration , 2001, Progress in Retinal and Eye Research.

[35]  R. Klein,et al.  Sunlight and the 5-year incidence of early age-related maculopathy: the beaver dam eye study. , 2001, Archives of ophthalmology.

[36]  N. Bressler Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. , 2001 .

[37]  M. Boulton,et al.  The role of oxidative stress in the pathogenesis of age-related macular degeneration. , 2000, Survey of ophthalmology.

[38]  L. V. Johnson,et al.  A potential role for immune complex pathogenesis in drusen formation. , 2000, Experimental eye research.

[39]  J D Gottsch,et al.  Oxidative damage and age-related macular degeneration. , 1999, Molecular vision.

[40]  H. Hammes,et al.  Nε(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration , 1999 .

[41]  R. Guymer,et al.  Changes in Bruch’s membrane and related structures with age , 1999, Progress in Retinal and Eye Research.

[42]  S. Horiuchi,et al.  Advanced glycation end products in age-related macular degeneration. , 1998, Archives of ophthalmology.

[43]  E. Rodriguez-Boulan,et al.  Morphogenesis of the Retinal Pigment Epithelium: Toward Understanding Retinal Degenerative Diseases a , 1998, Annals of the New York Academy of Sciences.

[44]  A. Kijlstra,et al.  Polarized secretion of IL‐6 and IL‐8 by human retinal pigment epithelial cells , 1998, Clinical and experimental immunology.

[45]  S. Line,et al.  Trace Element Status and Free Radical Defense in Elderly Rhesus Macaques (Macaca mulatta) with Macular Drusen , 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[46]  P T de Jong,et al.  Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. , 1994, Investigative ophthalmology & visual science.

[47]  A. Bird,et al.  Correlation between biochemical composition and fluorescein binding of deposits in Bruch's membrane. , 1992, Ophthalmology.

[48]  V. Sorrenti,et al.  Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age , 1992, Neurochemical Research.

[49]  A. Bird,et al.  Aging changes in Bruch's membrane. A histochemical and morphologic study. , 1990, Ophthalmology.

[50]  L. E. Rikans,et al.  Effect of aging on aqueous-phase antioxidants in tissues of male Fischer rats. , 1988, Biochimica et biophysica acta.

[51]  Robert B Sim,et al.  Assignment of complement components C4 binding protein (C4BP) and factor H (FH) to human chromosome 1q, using cDNA probes , 1988, Annals of human genetics.

[52]  Robert B Sim,et al.  The complete amino acid sequence of human complement factor H. , 1988, The Biochemical journal.

[53]  M. Vandewoude,et al.  Vitamin E status in a normal population: the influence of age. , 1987, Journal of the American College of Nutrition.

[54]  L. Feeney-Burns,et al.  Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. , 1984, Investigative ophthalmology & visual science.

[55]  C. Clemente HISTOLOGY OF THE HUMAN EYE : An Atlas and Textbook , 1973 .

[56]  K. Sandvig CENTRAL, AREOLAR CHOROIDAL ATROPHY , 1959, Acta ophthalmologica.

[57]  Neil M Bressler,et al.  Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2. , 2002, American journal of ophthalmology.

[58]  V. Perry,et al.  Dendritic cells in inflammatory responses in the CNS. , 1997, Advances in experimental medicine and biology.

[59]  F S Rosenthal,et al.  The long-term effects of visible light on the eye. , 1992, Archives of ophthalmology.

[60]  A. Augustin,et al.  Intestinal, hepatic and renal production of thiobarbituric acid reactive substances and myeloperoxidase activity after temporary aortic occlusion and reperfusion. , 1991, Life sciences.

[61]  R. W. Young Solar radiation and age-related macular degeneration. , 1988, Survey of ophthalmology.

[62]  A. Bird,et al.  Retinal pigment epithelial detachments in the elderly. , 1986, Transactions of the ophthalmological societies of the United Kingdom.