PURPOSE: To determine whether multivariate, functional principal component analysis of the size and shape of retinal pigment epithelial (RPE) cell morphology allows discrimination of mouse RPE genotypes and age. METHODS: Flatmounts of RPE sheets obtained from C57BL/6J (n = 50) and rd10 (n = 61) mice at postnatal days 30 to 720 were stained for zonula occludens-1 (ZO-1) and imaged with confocal microscopy. A total of 111 flatmounts were prepared. Twenty-one morphometric measurements were made on tiled, composite images of complete flatmounts, including cell location, area, and eccentricity, using automated image analysis software for quantitatively measuring cell phenotypes. RESULTS: In young (≤61-day-old) C57BL/6J mice, the RPE morphology resembled a regular hexagonal array of cells of uniform size throughout the retina, except near the ciliary body, where the shapes of RPE resembled a soft network. Old (≥180-day-old) C57BL/6J eyes had a subpopulation of large cells. A clear disruption of the regular cell size and shape appeared in rd10 mutants. Aspect ratio and cell area gave rise to principal components that predictively classified mouse age and genotype. CONCLUSIONS: Quantitative differences in the RPE sheet morphology allowed discrimination of rd10 from C57BL/6J strains despite the confounding effect of aging. This has implications for RPE sheet morphology as a potential early biomarker for diagnosis of eye disease and prognosis of the eye at early stages when disease is subtle. We conclude that an RPE cell's area and aspect ratio are very early quantitative indicators that predict progression to advanced RPE disease as manifested in rd10.
PURPOSE: To determine whether multivariate, functional principal component analysis of the size and shape of retinal pigment epithelial (RPE) cell morphology allows discrimination of mouse RPE genotypes and age. METHODS: Flatmounts of RPE sheets obtained from C57BL/6J (n = 50) and rd10 (n = 61) mice at postnatal days 30 to 720 were stained for zonula occludens-1 (ZO-1) and imaged with confocal microscopy. A total of 111 flatmounts were prepared. Twenty-one morphometric measurements were made on tiled, composite images of complete flatmounts, including cell location, area, and eccentricity, using automated image analysis software for quantitatively measuring cell phenotypes. RESULTS: In young (≤61-day-old) C57BL/6J mice, the RPE morphology resembled a regular hexagonal array of cells of uniform size throughout the retina, except near the ciliary body, where the shapes of RPE resembled a soft network. Old (≥180-day-old) C57BL/6J eyes had a subpopulation of large cells. A clear disruption of the regular cell size and shape appeared in rd10 mutants. Aspect ratio and cell area gave rise to principal components that predictively classified mouse age and genotype. CONCLUSIONS: Quantitative differences in the RPE sheet morphology allowed discrimination of rd10 from C57BL/6J strains despite the confounding effect of aging. This has implications for RPE sheet morphology as a potential early biomarker for diagnosis of eye disease and prognosis of the eye at early stages when disease is subtle. We conclude that an RPE cell's area and aspect ratio are very early quantitative indicators that predict progression to advanced RPE disease as manifested in rd10.
Authors: B Chang; N L Hawes; M T Pardue; A M German; R E Hurd; M T Davisson; S Nusinowitz; K Rengarajan; A P Boyd; S S Sidney; M J Phillips; R E Stewart; R Chaudhury; J M Nickerson; J R Heckenlively; J H Boatright Journal: Vision Res Date: 2007-01-30 Impact factor: 1.886
Authors: Luis M Escudero; Luciano da F Costa; Anna Kicheva; James Briscoe; Matthew Freeman; M Madan Babu Journal: Nat Commun Date: 2011-11-08 Impact factor: 14.919
Authors: Alia Rashid; Shagun K Bhatia; Karina I Mazzitello; Micah A Chrenek; Qing Zhang; Jeffrey H Boatright; Hans E Grossniklaus; Yi Jiang; John M Nickerson Journal: Adv Exp Med Biol Date: 2016 Impact factor: 2.622
Authors: Lena Iwai-Takekoshi; Anna Ramos; Ari Schaler; Samuel Weinreb; Richard Blazeski; Carol Mason Journal: J Comp Neurol Date: 2016-05-19 Impact factor: 3.215
Authors: K J Donaldson; W F Wu; H Skelton; S Markand; S Ferdous; J Sellers; M A Chrenek; I Gefke; S M Kim; J Rha; K L Liao; H E Grossniklaus; Y Jiang; J Kong; J H Boatright; John M Nickerson Journal: Adv Exp Med Biol Date: 2019 Impact factor: 2.622
Authors: Jeffrey H Boatright; Nupur Dalal; Micah A Chrenek; Christopher Gardner; Alison Ziesel; Yi Jiang; Hans E Grossniklaus; John M Nickerson Journal: Mol Vis Date: 2015-01-15 Impact factor: 2.367
Authors: Loris Nanni; Michelangelo Paci; Florentino Luciano Caetano dos Santos; Heli Skottman; Kati Juuti-Uusitalo; Jari Hyttinen Journal: PLoS One Date: 2016-02-19 Impact factor: 3.240
Authors: J Alan Gambril; Kenneth R Sloan; Thomas A Swain; Carrie Huisingh; Anna V Zarubina; Jeffrey D Messinger; Thomas Ach; Christine A Curcio Journal: Invest Ophthalmol Vis Sci Date: 2019-06-03 Impact factor: 4.799
Authors: Qing Zhang; Micah A Chrenek; Shagun Bhatia; Alia Rashid; Salma Ferdous; Kevin J Donaldson; Henry Skelton; Wenfei Wu; Thonnie Rose O See; Yi Jiang; Nupur Dalal; John M Nickerson; Hans E Grossniklaus Journal: Mol Vis Date: 2019-02-07 Impact factor: 2.367
Authors: Xian Zhang; Preston E Girardot; Jana T Sellers; Ying Li; Jiaxing Wang; Micah A Chrenek; Wenfei Wu; Henry Skelton; John M Nickerson; Machelle T Pardue; Jeffrey H Boatright Journal: Mol Vis Date: 2019-08-21 Impact factor: 2.367
Authors: Yong-Kyu Kim; Hanyi Yu; Vivian R Summers; Kevin J Donaldson; Salma Ferdous; Debresha Shelton; Nan Zhang; Micah A Chrenek; Yi Jiang; Hans E Grossniklaus; Jeffrey H Boatright; Jun Kong; John M Nickerson Journal: Invest Ophthalmol Vis Sci Date: 2021-02-01 Impact factor: 4.799