The Role of the Immune Response in Age-Related Macular Degeneration

Allergan, Inc., 2525 Dupont Drive, Irvine, CA 92612, USA.
International journal of inflammation 05/2013; 2013(5):348092. DOI: 10.1155/2013/348092
Source: PubMed


Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD.

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Available from: John P Atkinson, Sep 17, 2014
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    • "Several studies support the hypothesis that the immune system is involved in the pathogenesis of AMD, in concert with, or in addition to, other factors (Ambati et al., 2013; Whitcup et al., 2013). One factor that has captured our interest is bA3/A1-crystallin, which has been reported to be present in human drusen (Crabb et al., 2002), a precursor to AMD. "
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    ABSTRACT: Although chronic inflammation is believed to contribute to the pathology of age-related macular degeneration (AMD), knowledge regarding the events that elicit the change from para-inflammation to chronic inflammation in the pathogenesis of AMD is lacking. We propose here that lipocalin-2 (LCN2), a mammalian innate immunity protein that is trafficked to the lysosomes, may contribute to this process. It accumulates significantly with age in retinal pigment epithelial (RPE) cells of Cryba1 conditional knockout (cKO) mice, but not in control mice. We have recently shown that these mice, which lack βA3/A1-crystallin specifically in RPE, have defective lysosomal clearance. The age-related increase in LCN2 in the cKO mice is accompanied by increases in chemokine (C-C motif) ligand 2 (CCL2), reactive gliosis, and immune cell infiltration. LCN2 may contribute to induction of a chronic inflammatory response in this mouse model with AMD-like pathology.
    Aging cell 09/2014; 13(6). DOI:10.1111/acel.12274 · 6.34 Impact Factor
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    • "Whitcup et al. [33] pointed out that in general, protective variants result in less alternative pathway activity, whereas risk variants result in more alternative pathway activity. For example, a CFH polymorphism, which resulted in an amino acid substitution of histidine for tyrosine (Y402H), is strongly associated with the risk of AMD [29, 34, 35]. "
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    ABSTRACT: Inflammaging refers to a continuous, low-grade inflammation associated with aging. Such chronic inflammatory response could build up with time and gradually causes tissue damage. It is considered as one of the driving forces for many age-related diseases such as diabetes, atherosclerosis, age-related macular degeneration (AMD), and skin aging. There is mounting evidence that indicates aging is driven by the pro-inflammatory cytokines and substances produced by our body’s innate immune system. The macrophage and complement system, two important components of innate immune system, have attracted more and more attention since they appear to be involved in the pathogenesis of several inflammaging-associated diseases, such as AMD and atherosclerosis. This paper will review what we know about these two innate immune systems in the pathogenesis of AMD, atherosclerosis and skin aging.
    Inflammation & Allergy - Drug Targets (Formerly ?Current Drug Targets - Inflammation & Allergy) 07/2014; 13(3). DOI:10.2174/1871528113666140522112003
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    • "Second, there is evidence for immune surveillance in the subretinal space, and the retina becomes much more pro-inflammatory in acquired or inherited photoreceptor degenerations (1,28,29). There is a particularly extensive body of literature demonstrating a major role for inflammation in the pathogenesis of age-related macular degeneration (30,31). There is also some evidence that genetic or pharmacological modulation of the immune response may be beneficial in some types of photoreceptor disease (32). "
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    ABSTRACT: Vision is the most important human sense. It facilitates every major activity of daily living ranging from basic communication, mobility and independence to an appreciation of art and nature. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through some type of drug, gene or cell-based transplantation approach. In this review, we will discuss the current literature pertaining to retinal transplantation. We will focus on the use of induced pluripotent stem cells for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell replacement.
    Human Molecular Genetics 03/2014; 23(R1). DOI:10.1093/hmg/ddu124 · 6.39 Impact Factor
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