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Klin Monbl Augenheilkd 2019; 236(05): 672-681
DOI: 10.1055/s-0043-109891
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Autofluoreszenz des humanen retinalen Pigmentepithels in der normalen Alterung und bei altersbedingter Makuladegeneration: Histologie und Klinik

Autofluorescence of the Human Retinal Pigment Epithelium in Normal Aging and in Age-Related Macular Degeneration: Histology and Clinical Correlation
Thomas Ach
Augenklinik und Poliklinik, Universitätsklinikum Würzburg
,
Katharina Bermond
Augenklinik und Poliklinik, Universitätsklinikum Würzburg
› Author Affiliations
Further Information

Publication History

eingereicht 31 December 2016

akzeptiert 14 February 2017

Publication Date:
06 July 2017 (online)

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Zusammenfassung

Fundusautofluoreszenz(FAF)-Aufnahmen zählen seit beinahe 2 Jahrzehnten zur Routinediagnostik des menschlichen Augenhintergrunds. Die stetigen Weiterentwicklungen der Aufnahmetechniken ermöglichen heute eine sichere, nicht invasive, einfach durchführbare und reproduzierbare Darstellung des Augenhintergrunds. Die zugrunde liegende Technik macht sich die autofluoreszierenden Eigenschaften von Geweben, insbesondere des retinalen Pigmentepithels (RPE) und dessen Fluorophore, zunutze. Dadurch können FAF-Aufnahmen in hervorragender Weise Phänomene der normalen Alterung sowie krankheitsbedingte Veränderungen des Augenhintergrunds aufzeigen, aber auch Informationen zu Krankheitsverlauf und Therapiekontrolle liefern. In dieser Übersichtsarbeit sollen nach einer kurzen Einführung in die Basis der Fundusautofluoreszenz neueste grundlagenwissenschaftliche Kenntnisse zur Histologie im Hinblick auf altersbedingte und pathologische Veränderungen des RPE zusammengefasst werden, um so eine bessere Interpretation von FAF-Aufnahmen zu ermöglichen. Der Darstellung altersbedingter Veränderungen werden hierbei die pathologischen Veränderungen im Rahmen einer altersbedingten Makuladegeneration sowohl klinisch als auch auf histologischer Ebene gegenübergestellt.

Abstract

Autofluorescence images of the fundus have been part of the routine diagnostics of the human eye for almost two decades. Further development of imaging techniques makes fundus autofluorescence (FAF) imaging a safe, non-invasive, easy-to-perform and reproducible diagnostic tool. FAF uses the autofluorescent properties of tissues, in particular the retinal pigment epithelium (RPE) and its fluorophores. FAF images display phenomena of normal aging as well as disease-related changes of the fundus, but also can be used for monitoring retinal diseases and therapy. After a short introduction into the basics of FAF, the results of the latest histology studies regarding age-related and pathological changes of the human RPE will be summarized for a better understanding and interpretation of FAF images. The normal age-related changes of the RPE are contrasted with the pathological changes in age-related macular degeneration, both clinically and histologically.

Schlüsselwörter

retinales Pigmentepithel - Autofluoreszenz - Lipofuszin - altersbedingte Makuladegeneration - Mikroskopie - Histologie

Key words

retinal pigment epithelium - autofluorescence - lipofuscin - age-related macular degeneration - microscopy - histology
 

  • Literatur

  • 1 Delori FC, Dorey CK, Staurenghi G. et al. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci 1995; 36: 718-729
    Google Scholar
  • 2 Delori FC, Goger DG, Dorey CK. Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci 2001; 42: 1855-1866
    PubMedGoogle Scholar
  • 3 Von Ruckmann A, Fitzke FW, Bird AC. Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol 1995; 79: 407-412
    CrossrefPubMedGoogle Scholar
  • 4 Spaide R. Autofluorescence from the outer retina and subretinal space: hypothesis and review. Retina 2008; 28: 5-35
    CrossrefPubMedGoogle Scholar
  • 5 Sparrow JR, Gregory-Roberts E, Yamamoto K. et al. The bisretinoids of retinal pigment epithelium. Prog Retin Eye Res 2012; 31: 121-135
    CrossrefPubMedGoogle Scholar
  • 6 Tang PH, Kono M, Koutalos Y. et al. New insights into retinoid metabolism and cycling within the retina. Prog Retin Eye Res 2013; 32: 48-63
    CrossrefPubMedGoogle Scholar
  • 7 Katz ML, Robison jr. WG. What is lipofuscin? Defining characteristics and differentiation from other autofluorescent lysosomal storage bodies. Arch Gerontol Geriatr 2002; 34: 169-184
    CrossrefPubMedGoogle Scholar
  • 8 Katz ML, Gao CL, Rice LM. Formation of lipofuscin-like fluorophores by reaction of retinal with photoreceptor outer segments and liposomes. Mech Ageing Dev 1996; 92: 159-174
    CrossrefPubMedGoogle Scholar
  • 9 Ng KP, Gugiu B, Renganathan K. et al. Retinal pigment epithelium lipofuscin proteomics. Mol Cell Proteomics 2008; 7: 1397-1405
    CrossrefPubMedGoogle Scholar
  • 10 Feeney L. Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Invest Ophthalmol Vis Sci 1978; 17: 583-600
    PubMedGoogle Scholar
  • 11 Feeney-Burns L, Hilderbrand ES, Eldridge S. Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 1984; 25: 195-200
    PubMedGoogle Scholar
  • 12 Biesemeier A, Schraermeyer U, Eibl O. Chemical composition of melanosomes, lipofuscin and melanolipofuscin granules of human RPE tissues. Exp Eye Res 2011; 93: 29-39
    CrossrefPubMedGoogle Scholar
  • 13 Kim IT, Choi JB. Melanosomes of retinal pigment epithelium – distribution, shape, and acid phosphatase activity. Korean J Ophthalmol 1998; 12: 85-91
    CrossrefPubMedGoogle Scholar
  • 14 Keilhauer CN, Delori FC. Near-infrared autofluorescence imaging of the fundus: visualization of ocular melanin. Invest Ophthalmol Vis Sci 2006; 47: 3556-3564
    CrossrefPubMedGoogle Scholar
  • 15 Kellner U, Kellner S, Weber BH. et al. Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa. Eye 2009; 23: 1349-1359
    CrossrefPubMedGoogle Scholar
  • 16 Boulton M, Docchio F, Dayhaw-Barker P. et al. Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium. Vision Res 1990; 30: 1291-1303
    CrossrefPubMedGoogle Scholar
  • 17 Pollreisz A, Messinger JD, Sloan KR. et al. Visualizing retinal pigment epithelium (RPE) melanosomes, lipofuscin, melanolipofuscin (M, L, ML) in human eyes of different ages using 3-dimensional serial block face scanning electron microscopy (3D SBFSEM). Invest Ophthalmol Vis Sci 2016; 57
    PubMedGoogle Scholar
  • 18 Müller K, Heintzmann R, Hillenkamp J. et al. Intrazelluläre Autofluoreszenzspektren humaner retinaler Pigmentepithel-Zellen ex vivo beim normalen Altern und bei altersbedingter Makuladegeneration. Ophthalmologe 2016; DOG Abstracts.
    PubMedGoogle Scholar
  • 19 Schmitz-Valckenberg S, Holz FG, Bird AC. et al. Fundus autofluorescence imaging: review and perspectives. Retina 2008; 28: 385-409
    CrossrefPubMedGoogle Scholar
  • 20 Spaide RF. Autofluorescence imaging with the fundus camera. In: Holz FG, Schmitz-Valckenberg S, Spaide RF, Bird AC. eds. Atlas of Fundus Autofluorescence Imaging. Berlin, Heidelberg: Springer; 2007: 49-53
    Google Scholar
  • 21 Delori F, Greenberg JP, Woods RL. et al. Quantitative measurements of autofluorescence with the scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci 2011; 52: 9379-9390
    CrossrefPubMedGoogle Scholar
  • 22 Greenberg JP, Duncker T, Woods RL. et al. Quantitative fundus autofluorescence in healthy eyes. Invest Ophthalmol Vis Sci 2013; 54: 5684-5693
    CrossrefPubMedGoogle Scholar
  • 23 Delori FC. Spectrophotometer for noninvasive measurement of intrinsic fluorescence and reflectance of the ocular fundus. Appl Opt 1994; 33: 7439-7452
    CrossrefPubMedGoogle Scholar
  • 24 Polyak SL. The Retina: the Anatomy and the Histology of the Retina in Man, Ape, and Monkey, including the Consideration of visual Functions, the History of physiological Optics, and the histological Laboratory Technique. Chicago: University of Chicago; 1941
    Google Scholar
  • 25 Curcio CA, Sloan KR, Kalina RE. et al. Human photoreceptor topography. J Comp Neurol 1990; 292: 497-523
    CrossrefPubMedGoogle Scholar
  • 26 Ach T, Huisingh C, McGwin jr. G. et al. Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium. Invest Ophthalmol Vis Sci 2014; 55: 4832-4841
    CrossrefPubMedGoogle Scholar
  • 27 Ach T, Tolstik E, Messinger JD. et al. Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration. Invest Ophthalmol Vis Sci 2015; 56: 3242-3252
    CrossrefPubMedGoogle Scholar
  • 28 Starnes AC, Huisingh C, McGwin jr. G. et al. Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution. Vis Neurosci 2016; 33: e001
    CrossrefPubMedGoogle Scholar
  • 29 Feeney-Burns L, Berman ER, Rothman H. Lipofuscin of human retinal pigment epithelium. Am J Ophthalmol 1980; 90: 783-791
    CrossrefPubMedGoogle Scholar
  • 30 Delori FC, Fleckner MR, Goger DG. et al. Autofluorescence distribution associated with drusen in age-related macular degeneration. Invest Ophthalmol Vis Sci 2000; 41: 496-504
    PubMedGoogle Scholar
  • 31 Bindewald A, Bird AC, Dandekar SS. et al. Classification of fundus autofluorescence patterns in early age-related macular disease. Invest Ophthalmol Vis Sci 2005; 46: 3309-3314
    CrossrefPubMedGoogle Scholar
  • 32 Gliem M, Müller PL, Finger RP. et al. Quantitative fundus autofluorescence in early and intermediate age-related macular degeneration. JAMA Ophthalmol 2016; 134: 817-824
    CrossrefPubMedGoogle Scholar
  • 33 Brar M, Kozak I, Cheng L. et al. Correlation between spectral-domain optical coherence tomography and fundus autofluorescence at the margins of geographic atrophy. Am J Ophthalmol 2009; 148: 439-444
    CrossrefPubMedGoogle Scholar
  • 34 Bindewald A, Schmitz-Valckenberg S, Jorzik JJ. et al. Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration. Br J Ophthalmol 2005; 89: 874-878
    CrossrefPubMedGoogle Scholar
  • 35 Holz FG, Bellmann C, Margaritidis M. et al. Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1999; 237: 145-152
    CrossrefPubMedGoogle Scholar
  • 36 Holz FG, Bindewald-Wittich A, Fleckenstein M. et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol 2007; 143: 463-472
    CrossrefPubMedGoogle Scholar
  • 37 Zanzottera EC, Ach T, Huisingh C. et al. Visualizing retinal pigment epithelium phenotypes in the transition to atrophy in neovascular age-related macular degeneration. Retina 2016; 36 (Suppl. 01) S26-S39
    CrossrefPubMedGoogle Scholar
  • 38 Abdelfattah NS, Al-Sheikh M, Pitetta S. et al. Macular atrophy in neovascular age-related macular degeneration with monthly versus treat-and-extend ranibizumab: Findings from the TREX-AMD trial. Ophthalmology 2017; 124: 215-223
    CrossrefPubMedGoogle Scholar
  • 39 Zanzottera EC, Messinger JD, Ach T. et al. Subducted and melanotic cells in advanced age-related macular degeneration are derived from retinal pigment epithelium. Invest Ophthalmol Vis Sci 2015; 56: 3269-3278
    CrossrefPubMedGoogle Scholar
  • 40 Zanzottera EC, Messinger JD, Ach T. et al. The project MACULA retinal pigment epithelium grading system for histology and optical coherence tomography in age-related macular degeneration. Invest Ophthalmol Vis Sci 2015; 56: 3253-3268
    CrossrefPubMedGoogle Scholar
  • 41 Zanzottera EC, Ach T, Huisingh C. et al. Visualizing retinal pigment epithelium phenotypes in the transition to geographic atrophy in age-related macular degeneration. Retina 2016; 36 (Suppl. 01) S12-S25
    CrossrefPubMedGoogle Scholar
  • 42 Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 1988; 2: 552-577
    CrossrefPubMedGoogle Scholar
  • 43 Rudolf M, Vogt SD, Curcio CA. et al. Histologic basis of variations in retinal pigment epithelium autofluorescence in eyes with geographic atrophy. Ophthalmology 2013; 120: 821-828
    CrossrefPubMedGoogle Scholar
  • 44 Holz FG, Bellman C, Staudt S. et al. Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci 2001; 42: 1051-1056
    PubMedGoogle Scholar
  • 45 Sayegh RG, Simader C, Scheschy U. et al. A systematic comparison of spectral-domain optical coherence tomography and fundus autofluorescence in patients with geographic atrophy. Ophthalmology 2011; 118: 1844-1851
    CrossrefPubMedGoogle Scholar
  • 46 Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 2005; 80: 595-606
    CrossrefPubMedGoogle Scholar
  • 47 Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257
    CrossrefPubMedGoogle Scholar
  • 48 Von Ruckmann A, Fitzke FW, Bird AC. Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope. Invest Ophthalmol Vis Sci 1997; 38: 478-486
    PubMedGoogle Scholar
  • 49 Dunaief JL, Dentchev T, Ying G. et al. The role of apoptosis in age-related macular degeneration. Arch Ophthal 2002; 120: 1435-1442
    CrossrefPubMedGoogle Scholar
  • 50 Green WR. Key S3rd. Senile macular degeneration: a histopathologic study. Trans Am Ophthalmol Soc 1977; 75: 180
    PubMedGoogle Scholar
  • 51 Ooto S, Vongkulsiri S, Sato T. et al. Outer retinal corrugations in age-related macular degeneration. JAMA Ophthalmol 2014; 132: 806-813
    CrossrefPubMedGoogle Scholar