Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution
Open accessAbstract
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.
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RPE multinucleation could result from a cytokinesis defect.
“RPE multinucleation, which has been reported for humans ( 54 ), could result from a cytokinesis defect.”
From Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration (2017) · cites this paper as [54]
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“RPE multinucleation, which has been reported for humans (54), could result from a cytokinesis defect.”
Background
- Authors
- STARNES, A. C., HUISINGH, C., MCGWIN, G., SLOAN, K. R., ABLONCZY, Z., SMITH, R. T., CURCIO, C. A., & ACH, T.
- Affiliations
- University of Alabama at Birmingham (US)
- Medical University of South Carolina (US)
- NYU Langone Health (US)
- Corresponding author
- ACH, THOMAS
- ORCID
- Venue
- Visual Neuroscience
- Publisher
- Maximum Academic Press
- Published
- 2016
- Volume
- 33
- Pages
- e001-e001
- ISSN
- 0952-5238 (ISSN-L)
- 1469-8714
- PMC
- PMC4798426
- OpenAlex
- W2234999838
- Cited by
- 46
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 11 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 1
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Visual Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- EyeSight Foundation of Alabama
- Deutsche Forschungsgemeinschaft
- National Eye Institute (R01EY019065, EY019065, R01EY015520, R01EY06109, R01EY006109)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- retinal pigment epithelium, multinucleated cells, macula, fovea, perifovea, retinal eccentricity, lipofuscin autofluorescence, F-actin cytoskeleton, endoreplication, cell fusion, retinal aging
- MeSH terms
- Aged, Aged, 80 and over, Cell Nucleus, Humans, Macula Lutea, Middle Aged, Tissue Banks, Retinal Pigment Epithelium
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