September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
ABCB5 identifies RPE progenitor cells required for normal retinal development and aging
Author Affiliations & Notes
  • Bruce Ksander
    Harvard Medical School, Boston, Massachusetts, United States
    Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States
  • Andrew Hertsenberg
    Harvard Medical School, Boston, Massachusetts, United States
    Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States
  • Ruth Y Lewis
    Harvard Medical School, Boston, Massachusetts, United States
    Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States
  • Brian Wilson
    Transplant Research Program, Boston Children's Hospital, Boston, Massachusetts, United States
  • Gretchen Berg
    Division of Genetics, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Markus Hermann Frank
    Transplant Research Program, Boston Children's Hospital, Boston, Massachusetts, United States
    Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts, United States
  • Natasha Y Frank
    Division of Genetics, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Bruce Ksander, Rheacell GmbH & Co. KG (P), Rheacell GmbH & Co. KG (F), Ticeba GmbH (P); Andrew Hertsenberg, None; Ruth Lewis, None; Brian Wilson, None; Gretchen Berg, None; Markus Frank, Rheacell GmbH & Co. KG (P), Rheacell GmbH & Co. KG (C), Rheacell GmbH & Co. KG (R), Rheacell GmbH & Co. KG (S), Rheacell GmbH & Co. KG (F), Ticeba GmbH (P), Ticeba GmbH (C), Ticeba GmbH (R), Ticeba GmbH (S); Natasha Frank, Rheacell GmbH & Co. KG (P), Ticeba GmbH (P)
  • Footnotes
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Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Bruce Ksander, Andrew Hertsenberg, Ruth Y Lewis, Brian Wilson, Gretchen Berg, Markus Hermann Frank, Natasha Y Frank; ABCB5 identifies RPE progenitor cells required for normal retinal development and aging. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : RPE might contain subpopulations of progenitor cells with multipotent differentiation potential; however, no specific molecular marker for such subpopulations has been described to date. Recently, we identified ATP binding cassette member B5 (ABCB5) as a marker for mammalian limbal stem cells, with essential roles in normal corneal development and repair. In the current study, we describe that ABCB5 also identifies a novel progenitor subpopulation among RPE with essential functions in retinal development and regeneration.

Methods : RPE cells were recovered from choroidal flat mounts isolated from 2 months-old C57BL/6J mice and from human cadaveric donors. Analysis of ABCB5 expression in mouse and human RPE was done by dual-color flow cytometry using two distinct murine and human anti-ABCB5 monoclonal antibodies (mAb) described previously (Ksander et al., Nature 2014). Abcb5 knock out (KO) mice were generated as previously described (Ksander et al., Nature 2014) and maintained on a 129S6/SvEvTac/C57BL/6 mixed genetic background. Gender-matched littermates were used as controls for experimental analyses. Comparative histopathology of Abcb5 WT and Abcb5 KO retinas was done by examination of H&E-stained sections of 9 months old mice.

Results : Flow cytometric analyses of human and murine RPE cell suspensions revealed that ABCB5 was expressed in 2-8% of RPE cells. Additional studies demonstrated that a portion of ABCB5-positive cells did not express the marker of differentiated RPE cells, RPE65. Moreover, histological examination of Abcb5 KO mice revealed significantly reduced RPE cell numbers associated with abnormal RPE morphology and vacuolization. Additionally, Abcb5 KO animals also exhibited thinning and attenuation of the overlaying photoreceptor outer and inner segments, and reduced cell numbers in the outer nuclear layer.

Conclusions : ABCB5 identifies a novel progenitor cell population in RPE, which lacks expression of the RPE differentiation marker RPE65, but is essential for retinal development and regeneration.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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