Abstract
Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.
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References
Ajami B, Bennett JL, Krieger C et al (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543
Albini TA, Wang RC, Reiser B et al (2005) Microglial stability and repopulation in the retina. Br J Ophthalmol 89:901–903
Buschini E, Piras A, Nuzzi R et al (2011) Age related macular degeneration and drusen: neuroinflammation in the retina. Prog Neurobiol 95:14–25
Chen M, Muckersie E, Forrester JV et al (2010) Immune activation in retinal aging: a gene expression study. Invest Ophthalmol Vis Sci 51:5888–5896
Chinnery HR, McLenachan S, Humphries T et al (2012) Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX3CR1. Neurobiol Aging 33:1769–1776
Congdon NG, Friedman DS, Lietman T (2003) Important causes of visual impairment in the world today. JAMA 290:2057–2060
Congdon N, O’Colmain B, Klaver CC et al (2004) Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122:477–485
Damani MR, Zhao L, Fontainhas AM et al (2011) Age-related alterations in the dynamic behavior of microglia. Aging Cell 10:263–276
Friedman DS, O’Colmain BJ, Munoz B et al (2004a) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572
Friedman DS, Wolfs RC, O’Colmain BJ et al (2004b) Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol 122:532–538
Hefendehl JK, Neher JJ, Suhs RB et al (2014) Homeostatic and injury-induced microglia behavior in the aging brain. Aging Cell 13:60–69
Lee JE, Liang KJ, Fariss RN et al (2008) Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy. Invest Ophthalmol Vis Sci 49:4169–4176
Ma W, Zhao L, Fontainhas AM et al (2009) Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD. PLoS ONE 4:e7945
Ma W, Zhao L, Wong WT (2012) Microglia in the outer retina and their relevance to pathogenesis of age-related macular degeneration. Adv Exp Med Biol 723:37–42
Ma W, Coon S, Zhao L et al (2013a) A2E accumulation influences retinal microglial activation and complement regulation. Neurobiol Aging 34:943–960
Ma W, Cojocaru R, Gotoh N et al (2013b) Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation. Neurobiol Aging 34:2310–2321
Mouton PR, Long JM, Lei DL et al (2002) Age and gender effects on microglia and astrocyte numbers in brains of mice. Brain Res 956:30–35
Rutar M, Natoli R, Kozulin P et al (2011) Analysis of complement expression in light-induced retinal degeneration: synthesis and deposition of C3 by microglia/macrophages is associated with focal photoreceptor degeneration. Invest Ophthalmol Vis Sci 52:5347–5358
Santos AM, Calvente R, Tassi M et al (2008) Embryonic and postnatal development of microglial cells in the mouse retina. J Comp Neurol 506:224–239
Streit WJ, Xue QS (2009) Life and death of microglia. J Neuroimmune Pharmacol 4:371–379
Wang M, Wong WT (2014) Microglia-Muller cell interactions in the retina. Adv Exp Med Biol 801:333–338
Wang M, Ma W, Zhao L et al (2011) Adaptive Muller cell responses to microglial activation mediate neuroprotection and coordinate inflammation in the retina. J Neuroinflammation 8:173
Wang M, Wang X, Zhao L et al (2014) Macroglia–microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. J Neurosci 34:3793–3806
Wax MB, Tezel G (2009) Immunoregulation of retinal ganglion cell fate in glaucoma. Exp Eye Res 88:825–830
Wong WT (2013) Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation. Front Cell Neurosci 7:22
Xu H, Chen M, Manivannan A et al (2008) Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice. Aging Cell 7:58–68
Xu H, Chen M, Forrester JV (2009) Para-inflammation in the aging retina. Prog Retin Eye Res 28:348–368
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Ma, W., Wong, W. (2016). Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease. In: Bowes Rickman, C., LaVail, M., Anderson, R., Grimm, C., Hollyfield, J., Ash, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 854. Springer, Cham. https://doi.org/10.1007/978-3-319-17121-0_11
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DOI: https://doi.org/10.1007/978-3-319-17121-0_11
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