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Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution

Published online by Cambridge University Press:  12 January 2016

AUSTIN C. STARNES ,
CARRIE HUISINGH ,
GERALD MCGWIN JR. ,
KENNETH R. SLOAN ,
ZSOLT ABLONCZY ,
R. THEODORE SMITH ,
CHRISTINE A. CURCIO  and
THOMAS ACH
AUSTIN C. STARNES
Affiliation:
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
CARRIE HUISINGH
Affiliation:
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
GERALD MCGWIN JR.
Affiliation:
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
KENNETH R. SLOAN
Affiliation:
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama Department of Computer and Information Sciences, University of Alabama at Birmingham, Birmingham, Alabama
ZSOLT ABLONCZY
Affiliation:
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
R. THEODORE SMITH
Affiliation:
Department of Ophthalmology, New York University School of Medicine, New York, New York
CHRISTINE A. CURCIO
Affiliation:
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
THOMAS ACH*
Affiliation:
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama Department of Ophthalmology, University Hospital Würzburg, Würzburg, Bavaria, Germany
*
*Address correspondence to: Thomas Ach, MD, University Hospital Würzburg, Department of Ophthalmology, Josef-Schneider-Straße 11, 97080 Würzburg, Germany, E-mail: ach_t@ukw.de
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Abstract

Background: The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Methods: Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. Results: A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. Conclusion: This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.

Keywords

Retinal pigment epitheliumCell nucleusBi-nucleateMulti-nucleate
Type
Research Article
Information
Visual Neuroscience , Volume 33 , 2016 , E001
Copyright
Copyright © Cambridge University Press 2016 

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References

Ablonczy, Z., Higbee, D., Anderson, D.M., Dahrouj, M., Grey, A.C., Gutierrez, D., Koutalos, Y., Schey, K.L., Hanneken, A. & Crouch, R.K. (2013). Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium. Investigative Ophthalmology & Visual Science 54, 5535–5542.Google Scholar
Abmayr, S.M. & Pavlath, G.K. (2012). Myoblast fusion: Lessons from flies and mice. Development 139, 641–656.Google Scholar
Ach, T., Huisingh, C., McGwin, G. Jr., Messinger, J.D., Zhang, T., Bentley, M.J., Gutierrez, D.B., Ablonczy, Z., Smith, R.T., Sloan, K.R. & Curcio, C.A. (2014). Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium. Investigative Ophthalmology & Visual Science 55, 4832–4841.Google Scholar
Al-Hussaini, H., Kam, J.H., Vugler, A., Semo, M. & Jeffery, G. (2008). Mature retinal pigment epithelium cells are retained in the cell cycle and proliferate in vivo. Molecular Vision 14, 1784–1791.Google Scholar
Al-Hussaini, H., Schneiders, M., Lundh, P. & Jeffery, G. (2009). Drusen are associated with local and distant disruptions to human retinal pigment epithelium cells. Experimental Eye Research 88, 610–612.Google Scholar
Bodenstein, L. & Sidman, R.L. (1987). Growth and development of the mouse retinal pigment epithelium. I. Cell and tissue morphometrics and topography of mitotic activity. Developmental Biology 121, 192–204.Google Scholar
Bone, R.A., Gibert, J.C. & Mukherjee, A. (2012). Light distributions on the retina: Relevance to macular pigment photoprotection. Acta Biochimica Polonica 59, 91–96.Google Scholar
Celton-Morizur, S., Merlen, G., Couton, D., Margall-Ducos, G. & Desdouets, C. (2009). The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. The Journal of Clinical Investigation 119, 1880–1887.Google ScholarPubMed
Comai, L. (2005). The advantages and disadvantages of being polyploid. Nature Reviews Genetics 6, 836–846.CrossRefGoogle ScholarPubMed
Curcio, C.A., Sloan, K.R., Kalina, R.E. & Hendrickson, A.E. (1990). Human photoreceptor topography. The Journal of Comparative Neurology 292, 497–523.CrossRefGoogle ScholarPubMed
Ding, J.D., Johnson, L.V., Herrmann, R., Farsiu, S., Smith, S.G., Groelle, M., Mace, B.E., Sullivan, P., Jamison, J.A., Kelly, U., Harrabi, O., Bollini, S.S., Dilley, J., Kobayashi, D., Kuang, B., Li, W., Pons, J., Lin, J.C. & Bowes Rickman, C.. (2011). Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proceedings of the National Academy of Sciences of the United States of America 108, E279–E287.Google Scholar
Duncker, T., Greenberg, J.P., Sparrow, J.R., Smith, R.T., Quigley, H.A. & Delori, F.C. (2012). Visualization of the optic fissure in short-wavelength autofluorescence images of the fundus. Investigative Ophthalmology & Visual Science 53, 6682–6686.CrossRefGoogle ScholarPubMed
Feeney, L. (1978). Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Investigative Ophthalmology & Visual Science 17, 583–600.Google Scholar
Fleming, P.A., Harman, A.M. & Beazley, L.D. (1997). Changing topography of the RPE resulting from experimentally induced rapid eye growth. Visual Neuroscience 14, 449–461.CrossRefGoogle ScholarPubMed
Hirsch, J. & Curcio, C.A. (1989). The spatial resolution capacity of human foveal retina. Vision Research 29, 1095–1101.CrossRefGoogle ScholarPubMed
Joubès, J. & Chevalier, C. (2000). Endoreduplication in higher plants. In Inzé, Dirk The Plant Cell Cycle, pp. 191–201. Springer: The Netherlands.Google Scholar
Kooijman, A.C. (1983). Light distribution on the retina of a wide-angle theoretical eye. Journal of the Optical Society of America 73, 1544–1550.Google Scholar
Kudryavtsev, B., Kudryavtseva, M., Sakuta, G. & Stein, G. (1993). Human hepatocyte polyploidization kinetics in the course of life cycle. Virchows Archiv B 64, 387–393.Google Scholar
Lacroix, B. & Maddox, A.S. (2012). Cytokinesis, ploidy and aneuploidy. The Journal of pathology 226, 338–351.Google Scholar
Pandit, S.K., Westendorp, B. & de Bruin, A. (2013). Physiological significance of polyploidization in mammalian cells. Trends in Cell Biology 23, 556–566.Google Scholar
Pflibsen, K.P., Pomerantzeff, O. & Ross, R.N. (1988). Retinal illuminance using a wide-angle model of the eye. Journal of the Optical Society of America. A, Optics and Image Science 5, 146–150.Google Scholar
Provis, J.M., Dubis, A.M., Maddess, T. & Carroll, J. (2013). Adaptation of the central retina for high acuity vision: Cones, the fovea and the avascular zone. Progress in Retinal and Eye Research 35, 63–81.CrossRefGoogle ScholarPubMed
Rapaport, D.H., Rakic, P., Yasamura, D. & LaVail, M.M. (1995). Genesis of the retinal pigment epithelium in the macaque monkey. The Journal of Comparative Neurology 363, 359–376.Google Scholar
Robb, R.M. (1985). Regional changes in retinal pigment epithelial cell density during ocular development. Investigative Ophthalmology & Visual Science 26, 614–620.Google Scholar
Scoles, D., Sulai, Y.N., Langlo, C.S., Fishman, G.A., Curcio, C.A., Carroll, J. & Dubra, A. (2014). In vivo imaging of human cone photoreceptor inner segments. Investigative Ophthalmology & Visual Science 55, 4244–4251.Google Scholar
Shi, G., Maminishkis, A., Banzon, T., Jalickee, S., Li, R., Hammer, J. & Miller, S.S. (2008). Control of chemokine gradients by the retinal pigment epithelium. Investigative Ophthalmology & Visual Science 49, 4620–4630.Google Scholar
Storchova, Z. & Pellman, D. (2004). From polyploidy to aneuploidy, genome instability and cancer. Nature Reviews Molecular Cell Biology 5, 45–54.CrossRefGoogle ScholarPubMed
Strauss, O. (2005). The retinal pigment epithelium in visual function. Physiological Reviews 85, 845–881.Google Scholar
Teitelbaum, S.L. & Ross, F.P. (2003). Genetic regulation of osteoclast development and function. Nature Reviews Genetics 4, 638–649.CrossRefGoogle Scholar
Ts'o, M.O. & Friedman, E. (1967). The retinal pigment epithelium. I. Comparative histology. Archives of Ophthalmology 78, 641–649.Google Scholar
Ts'o, M.O. & Friedman, E. (1968). The retinal pigment epithelium. 3. Growth and development. Archives of Ophthalmology 80, 214–216.Google Scholar
Vignery, A. (2000). Osteoclasts and giant cells: Macrophage-macrophage fusion mechanism. International Journal of Experimental Pathology 81, 291–304.Google Scholar
Vignery, A. (2005). Macrophage fusion the making of osteoclasts and giant cells. The Journal of Experimental Medicine 202, 337–340.Google Scholar
Walsh, S., Ponten, A., Fleischmann, B.K. & Jovinge, S. (2010). Cardiomyocyte cell cycle control and growth estimation in vivo–an analysis based on cardiomyocyte nuclei. Cardiovascular Research 86, 365–373.Google Scholar
Wang, L., Li, C.M., Rudolf, M., Belyaeva, O.V., Chung, B.H., Messinger, J.D., Kedishvili, N.Y. & Curcio, C.A. (2009). Lipoprotein particles of intraocular origin in human bruch membrane: An unusual lipid profile. Investigative Ophthalmology & Visual Science 50, 870–877.Google Scholar
Williams, D.R. (1985). Aliasing in human foveal vision. Vision Research 25, 195–205.Google Scholar
Ziegler, A., Kastner, C. & Blettner, M. (1998). The Generalised estimating equations: An annotated bibliography. Biometrical Journal 40, 115–139.Google Scholar