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Microglia in the Aging Retina

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

In the healthy retina, microglial cells represent a self-renewing population of innate immune cells, which constantly survey their microenvironment. Equipped with receptors, a microglial cell detects subtle cellular damage and rapidly responds with activation, migration, and increased phagocytic activity. While the involvement of microglial cells has been well characterized in monogenic retinal disorders, it is still unclear how they contribute to the onset of retinal aging disorders including age-related macular degeneration (AMD). There is evidence, that microglial activation is not solely a secondary manifestation of retinal tissue damage in age-related disorders. Thus, work in the aging rodent and human retina suggests that long-lived and genetically predisposed microglia transform into a dystrophic state, with loss of neuroprotective functions. In this concept, malfunction of aging microglia can trigger a chronic low-grade inflammatory environment that favors the onset and progression of retinal degeneration.

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References

  1. Stone J, Maslim J, Valter-Kocsi K, Mervin K, Bowers F, Chu Y et al (1999) Mechanisms of photoreceptor death and survival in mammalian retina. Prog Retin Eye Res 18(6):689–735

    Article  PubMed  CAS  Google Scholar 

  2. Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358(24):2606–2617

    Article  PubMed  CAS  Google Scholar 

  3. Swaroop A, Branham KEH, Chen W, Abecasis G (2007) Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. Hum Mol Genet 16:R174–182

    Google Scholar 

  4. Karlstetter M, Ebert S, Langmann T (2010) Microglia in the healthy and degenerating retina: insights from novel mouse models. Immunobiology 215(9–10):685–691

    Article  PubMed  CAS  Google Scholar 

  5. Gupta N, Brown KE, Milam AH (2003) Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res 76(4):463–471

    Article  PubMed  CAS  Google Scholar 

  6. Ma W, Zhao L, Fontainhas AM, Fariss RN, Wong WT (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(11):e7945

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Chen M, Forrester J (2009) Para-inflammation in the aging retina. Prog Retin Eye Res 28(5):348–368

    Article  PubMed  CAS  Google Scholar 

  8. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Flanary BE, Sammons NW, Nguyen C, Walker D, Streit WJ (2007) Evidence that aging and amyloid promote microglial cell senescence. Rejuvenation Res 10(1):61–74

    Article  PubMed  CAS  Google Scholar 

  10. Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120(4):437–447

    Article  PubMed  CAS  Google Scholar 

  11. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318

    Article  PubMed  CAS  Google Scholar 

  12. Damani MR, Zhao L, Fontainhas AM, Amaral J, Fariss RN, Wong WT (2010) Age-related alterations in the dynamic behavior of microglia. Glia 10:263–276

    Google Scholar 

  13. Streit WJ (2006) Microglial senescence: does the brain’s immune system have an expiration date? Trends Neurosci 29(9):506–510

    Article  PubMed  CAS  Google Scholar 

  14. Glenn JV, Stitt AW (2009) The role of advanced glycation end products in retinal ageing and disease. Biochim Biophys Acta 1790(10):1109–1116

    Article  PubMed  CAS  Google Scholar 

  15. Ma W, Coon S, Zhao L, Fariss RN, Wong WT (2012) A2E accumulation influences retinal microglial activation and complement regulation. Neurobiol Aging 34(3):943–960

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Fang F, Lue LF, Yan S, Xu H, Luddy JS, Chen D et al (2010) RAGE-dependent signaling in microglia contributes to neuroinflammation, Aβ accumulation, and impaired learning/memory in a mouse model of Alzheimer’s disease. FASEB J 24(4):1043–1055

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Shanmugam N, Figarola JL, Li Y, Swiderski PM, Rahbar S, Natarajan R (2008) Proinflammatory effects of advanced lipoxidation end products in monocytes. Diabetes 57(4):879–888

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C et al (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308(5720):385–389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Weismann D, Hartvigsen K, Lauer N, Bennett KL, Scholl HPN, Charbel Issa P et al (2011) Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478(7367):76–81

    Article  PubMed  CAS  Google Scholar 

  20. Linnartz B, Neumann H (2013) Microglial activatory (immunoreceptor tyrosine-based activation motif)- and inhibitory (immunoreceptor tyrosine-based inhibition motif)-signaling receptors for recognition of the neuronal glycocalyx. Glia 61(1):37–46

    Article  PubMed  Google Scholar 

  21. Moseley R, Waddington RJ, Embery G (1997) Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim Biophys Acta 1362(2–3):221–231

    Article  PubMed  CAS  Google Scholar 

  22. Moseley R, Waddington R, Evans P, Halliwell B, Embery G (1995) The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro. Biochim Biophys Acta 1244(2–3):245–252

    Article  PubMed  Google Scholar 

  23. Linnartz B, Kopatz J, Tenner AJ, Neumann H (2012) Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by microglia. J Neurosci 32(3):946–952

    Article  PubMed  CAS  Google Scholar 

  24. Takahashi K (2005) Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med 201(4):647–657

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E et al (2012) TREM2 variants in Alzheimer’s disease. N Engl J Med 368(2):117–127

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Jonsson T, Stefansson H, Ph D SS, Jonsdottir I, Jonsson PV, Snaedal J et al (2012) Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 368(2):107–116

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Chen M, Muckersie E, Forrester JV, Xu H (2010) Immune activation in retinal aging: a gene expression study. Invest Ophthalmol Vis Sci 51(11):5888–5896

    Article  PubMed  Google Scholar 

  28. Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K (2007) Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 55(4):412–424

    Article  PubMed  Google Scholar 

  29. Mustafi D, Maeda T, Kohno H, Nadeau JH, Palczewski K (2012) Inflammatory priming predisposes mice to age-related retinal degeneration. J Clin Invest 122(8):2989–3001

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Ebert S, Walczak Y, Remé C, Langmann T (2012) Microglial activation and transcriptomic changes in the blue light-exposed mouse retina. Adv Exp Med Biol 723:619–632

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, University of Cologne, Kerpener Straße 62, D-50924, Cologne, Germany

    Marcus Karlstetter & Thomas Langmann

Authors
  1. Marcus Karlstetter
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  2. Thomas Langmann
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Corresponding author

Correspondence to Thomas Langmann .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Karlstetter, M., Langmann, T. (2014). Microglia in the Aging Retina. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_27

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_27

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

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