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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

Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama Department of Computer and Information Sciences, University of Alabama at Birmingham, Birmingham, Alabama
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
Department of Ophthalmology, New York University School of Medicine, New York, New York
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama
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:


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.

Research Article
Copyright © Cambridge University Press 2016 

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