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Austin Starnes, Carrie E Huisingh, Kristen M Hammack, Jeffrey D Messinger, Gerald McGwin, Kenneth R Sloan, Christine A Curcio, Thomas Ach; Multinucleate RPE cells in normal human macula exhibit exquisite regional specificity. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2371.
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© ARVO (1962-2015); The Authors (2016-present)
Human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated, determined in a limited series of eyes (PMID 4963693). To assess the potential importance to human vision of multinucleated (MN) RPE cells, we report frequencies and spatial distribution from RPE flatmounts.
Nineteen RPE flatmounts (PMID 25034602; 9<51yrs, 10>80 yrs) were imaged at 12 predefined locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, and nasal). At each location, image stacks were taken using a confocal fluorescence microscope (488 nm excitation for lipofuscin AF and 647 nm excitation for the phalloidin labeled F-actin cytoskeleton). Cell nuclei, devoid of AF, were manually marked using a custom FIJI plug-in. Cell borders were defined by Voronoi regions. Poisson regression models using generalized estimating equations (GEE) were used to compare the mean number of nuclei per cell among eccentricity/quadrant groups and by age.
A total of 11403 RPE cells at 200 locations were analyzed: 94.66 % mono-, 5.31% bi-, 0.02% trinucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant spatial differences. Highest frequencies of MN cells were found in the perifovea (9.9%) and periphery (6.8%), while the fovea lacked MN cells almost entirely (Figure). Nasal quadrant had significantly more MN cells compared to other quadrants, at all eccentricities.
This is the first study to demonstrate that the human macula contains MN RPE cells, which might be due to endoreplication, cell fusion, or incomplete cell division. Their near-absence in the fovea suggests that this seemingly homogenous epithelium actually reflects the specialized needs of foveal cones in sustaining high-acuity vision. The perifovea is where rod photoreceptor density and AF are both high. Nasal quadrant contains the papillomacular area and closure of optic fissure. High frequency of MN cells in perifovea might reflect specific requirements of retinal metabolism, markers of past developmental processes, and other mechanisms to be explored in further studies.
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