RT Journal Article
A1 Carido, Madalena
A1 Zhu, Yu
A1 Postel, Kai
A1 Benkner, Boris
A1 Cimalla, Peter
A1 Karl, Mike O.
A1 Kurth, Thomas
A1 Paquet-Durand, François
A1 Koch, Edmund
A1 Münch, Thomas A.
A1 Tanaka, Elly M.
A1 Ader, Marius
T1 Characterization of a Mouse Model With Complete RPE Loss and Its Use for RPE Cell Transplantation
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2014
DO 10.1167/iovs.14-14325
VO 55
IS 8
SP 5431
OP 5444
SN 1552-5783
AB    Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the usefulness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells.    Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell–derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were analyzed 3 weeks later.    Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abolished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments.    Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.  
RD 4/22/2021
UL https://doi.org/10.1167/iovs.14-14325