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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY014038-01
Application #
6460359
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Dudley, Peter A
Project Start
2002-05-01
Project End
2006-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
1
Fiscal Year
2002
Total Cost
$363,420
Indirect Cost
Name
University of Utah
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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
McGill, Trevor J; Prusky, Glen T; Douglas, Robert M et al. (2007) Intraocular CNTF reduces vision in normal rats in a dose-dependent manner. Invest Ophthalmol Vis Sci 48:5756-66
Girman, S V; Lund, R D (2007) Most superficial sublamina of rat superior colliculus: neuronal response properties and correlates with perceptual figure-ground segregation. J Neurophysiol 98:161-77
McGill, Trevor J; Lund, Raymond D; Douglas, Robert M et al. (2007) Syngeneic Schwann cell transplantation preserves vision in RCS rat without immunosuppression. Invest Ophthalmol Vis Sci 48:1906-12
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
Wang, Shaomei; Lu, Bin; Lund, Raymond D (2005) Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell-based therapy. J Comp Neurol 491:400-17

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