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Graefe's Archive for Clinical and Experimental Ophthalmology

Published in:

01-11-2018 | Basic Science

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells

Authors: Biju B. Thomas, Danhong Zhu, Tai-Chi Lin, Young Chang Kim, Magdalene J. Seiler, Juan Carlos Martinez-Camarillo, Bin Lin, Yousuf Shad, David R. Hinton, Mark S. Humayun

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 11/2018

Abstract

Purpose

To create new immunodeficient Royal College of Surgeons (RCS) rats by introducing the defective MerTK gene into athymic nude rats.

Methods

Female homozygous RCS (RCS-p+/RCS-p+) and male nude rats (Hsd:RH-Foxn1^mu, mutation in the foxn1 gene; no T cells) were crossed to produce heterozygous F1 progeny. Double homozygous F2 progeny obtained by crossing the F1 heterozygotes was identified phenotypically (hair loss) and genotypically (RCS-p+ gene determined by PCR). Retinal degenerative status was confirmed by optical coherence tomography (OCT) imaging, electroretinography (ERG), optokinetic (OKN) testing, superior colliculus (SC) electrophysiology, and by histology. The effect of xenografts was assessed by transplantation of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and human-induced pluripotent stem cell-derived RPE (iPS-RPE) into the eye. Morphological analysis was conducted based on hematoxylin and eosin (H&E) and immunostaining. Age-matched pigmented athymic nude rats were used as control.

Results

Approximately 6% of the F2 pups (11/172) were homozygous for RCS-p+ gene and Foxn1^mu gene. Homozygous males crossed with heterozygous females resulted in 50% homozygous progeny for experimentation. OCT imaging demonstrated significant loss of retinal thickness in homozygous rats. H&E staining showed photoreceptor thickness reduced to 1–3 layers at 12 weeks of age. Progressive loss of visual function was evidenced by OKN testing, ERG, and SC electrophysiology. Transplantation experiments demonstrated survival of human-derived cells and absence of apparent immune rejection.

Conclusions

This new rat animal model developed by crossing RCS rats and athymic nude rats is suitable for conducting retinal transplantation experiments involving xenografts.

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Title: A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells
Authors: Biju B. Thomas
Danhong Zhu
Tai-Chi Lin
Young Chang Kim
Magdalene J. Seiler
Juan Carlos Martinez-Camarillo
Bin Lin
Yousuf Shad
David R. Hinton
Mark S. Humayun
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 11/2018
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-018-4134-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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