It is planned to limit the deleterious consequences of retinal dystrophy in RCS rats in transgenic rats with human rhodopsin mutation by introducing cells to the subretinal space. There are five specific aims. 1) To study efficacy of alternatives to fresh RPE cells in preventing photoreceptor degeneration resulting from a defect in the photoreceptors themselves or in the adjacent RPE. Immortalized human RPE cell lines and Schwann cells will be used as donor cells, transplanting them either to RCS rats or to transgenic rats with mutations in the rhodopsin gene causing a moderate rate of degeneration. 2) To examine how grafted cells settle in the subretinal space, how they interrelate with adjacent cells and how long they survive. 3) To examine how numbers and distribution of grafted cells correspond with the degree of photoreceptor rescue. 4) To examine how photoreceptor rescue correlates with spared central visual function. 5) To use grafted cells as vectors for introduced molecules. The purpose of the work is twofold. First, it will provide essential background data necessary in assessing the feasibility of developing a transplantation approach for patients with retinal degenerative diseases such as retinitis pigmentosa and age related macular degeneration. Second, it will also approach the basic biology of degeneration and repair, which in itself will provide insights into factors that may influence photoreceptor survival and perhaps obviate the need for transplantation as a potential therapy.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VISC (01))
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Dudley, Peter A
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Wang, Shaomei; Girman, Sergej; Lu, Bin et al. (2008) Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration. Invest Ophthalmol Vis Sci 49:3201-6
Wang, Shaomei; Lu, Bin; Girman, Sergej et al. (2008) Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration. Invest Ophthalmol Vis Sci 49:416-21
Pinilla, Isabel; Cuenca, Nicolas; Sauve, Yves et al. (2007) Preservation of outer retina and its synaptic connectivity following subretinal injections of human RPE cells in the Royal College of Surgeons rat. Exp Eye Res 85:381-92
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Zambarakji, H J; Keegan, D J; Holmes, T M et al. (2006) High resolution imaging of fluorescein patterns in RCS rat retinae and their direct correlation with histology. Exp Eye Res 82:164-71
King, Carolyn; Bartlett, Carole; Sauve, Yves et al. (2006) Retinal ganglion cell axons regenerate in the presence of intact sensory fibres. Neuroreport 17:195-9
Sauve, Y; Pinilla, I; Lund, R D (2006) Partial preservation of rod and cone ERG function following subretinal injection of ARPE-19 cells in RCS rats. Vision Res 46:1459-72
Pinilla, I; Lund, R D; Lu, B et al. (2005) Measuring the cone contribution to the ERG b-wave to assess function and predict anatomical rescue in RCS rats. Vision Res 45:635-41

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