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Biju Thomas, Cindy H. Shih, Danhong Zhu, Juan Carlos Martinez, David R Hinton, Mark S Humayun; A New Immunodeficient Dystrophic RCS Rat Model for Transplantation Studies Using Human Derived Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3735. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To introduce the mutation of Mertk gene present in dystrophic Royal College of Surgeon (RCS) rat into non-dystrophic Athymic nude rat to develop an immunodeficient RCS rat model with retinal degeneration (nude dystrophic RCS rats). This model can be used to minimize the adverse effects of xenograft transplantation.
Female homozygous Pigmented dystrophic RCS rats (RCS-p+/ RCS-p+) were crossed with male pigmented non-dystrophic Athymic nude rats (Hsd:RH-Fox1^rnu/Fox1^rnu, no T-cells). Genotyping for Fox1 and RCS-p+ gene were determined by PCR analysis. Retinal degenerative disease condition was assessed by OCT imaging and optokinetic (OKN) visual behavioral testing. Morphological analysis of the retina was based on haematoxylin and eosin (H&E) staining . Age-matched normal pigmented non-dystrophic Athymic Nude rats were used as controls for the above experiments.
The homozygous Fox1 gene was identified based on the hairless phenotype. The homozygous RCS-p+ gene was identified based on PCR analysis. Approximately 6% of the F2 pups (11/172) were homozygous for both RCS-p+ gene and Foxn1 gene (nude dystrophic RCS rats). OCT imaging at 12 weeks of age demonstrated significant loss of retinal thickness in double homozygous RCS rats (p<0.0001, 254.10±3.06 µm non-dystrophic nude retina vs 197.20±2.61 µm nude dystrophic retina). This was further confirmed by histological evaluation of the eye. Based on H&E staining, photoreceptor layer thickness in 12 week old nude dystrophic RCS rats was limited to two to three layers in the peripheral region of the retina and to a single layer in the central region of the retina. Visual functional deficit in nude dystrophic RCS rats was evidenced by severe loss of OKN visual acuity.
A new immunodeficient nude dystrophic RCS rat model is developed by crossing female homozygous Pigmented dystrophic RCS rats with male pigmented non-dystrophic Athymic nude rats. This newly created rat model can be extremely useful to test the effect of human cell transplantation studies without interference of immunosuppression.
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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