Abstract

DO.05.04

Retinal function following application of neural stem cells into a Rhodopsin knock-in mouse model of retinal dystrophy

Rüther K.¹, Skosyrski S.¹, Bartsch U.^2
1Charité - Universitätsmedizin Berlin, Augenklinik, Campus Virchow-Klinikum; ²Transplantationslabor der UKE-Augenklinik Hamburg

Objective: A rhodopsin knock-in (KI) mouse model* was investigated concerning the effects of intraretinal transplantation of neural stem cells (NSCs) on retinal function. In a first step we were interested in the safety of the transplantation procedure. *Provided by Wim de Grip, Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University of Nijmegen Medical School
Methods: NSCs were isolated from the striatum of embryonic EGFP*-transgenic mice. Cells from the fifth passage were intraretinally injected into 10 days old (9 KI and 9 wild-type (WT) mice) and 30 days old (8 KI and 8 WT) mice. The contralateral eyes of each animal received vehicle injections, and served as controls. Mice were examined with 2,5 and 4,5 months of age by full-field electroretinogram (ERG) recordings. *Enhanced green fluorescent protein
Results: Four out of 16 mice that received injections at 30 days of age developed phtisis bulbi in either a cell- or a sham-injected eye. Interestingly, this was not observed in any of the 18 mice that were manipulated at 10 days of age. Some mice from both, the 10-days-old group and the 30-days-old group developed transparency defects. While WT mice from the 10-days-old group showed lower ERG responses in the cell- than in the vehicle-injected eyes, the opposite was true for KI mice. In the 30-days-old group, in comparison, both WT and mutant mice showed slightly lower ERG responses in cell-injected eyes when compared to vehicle-injected eyes. However, none of these differences reached statistical significance.
Conclusions: Intraretinal injections may lead to opacities of the transparent media of the mouse eye. ERG recordings allow the functional characterisation of experimental animals that develop such secondary complications. Altogether, we did not observe any significant beneficial effect of intraretinal neural stem cell transplantations on retinal function in rhodopsin knock-in mice. However, in the 10-days-old group, there was a slight increase in the ERG response in cell-injected eyes when compared to vehicle-injected eyes. Supported by the Foundation of the Pro Retina Deutschland e.V.

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