This research examines how transplanted retinal pigment epithelium (RPE) and photoreceptors contribute to the restoration of structure and function in animal models of retinal degeneration. In RCS rats RPE transplants, bFGF and sham surgery retard the photoreceptor degeneration. We test a hypothesis that could explain these effects by the same mechanism, the removal by macrophages of a toxic factor produced by the pile up of outer segments in this genetic disease. We test whether bFGF recruits macrophages in the retina and whether these macrophages are related in space and time to the photoreceptor saving. We compare the ultrastructure of the photoreceptors rescued by bFGF, determine their proximity to macrophages; and compare them to photoreceptors saved by RPE transplants. Transplanted photoreceptors survive within the receptorless retinas of rd mice and RCS rats for at least three months. We determine whether transplants of retinal microaggregates lead to better photoreceptor preservation and function than dissociated photoreceptors when controlled for identical neonatal age. The ultrastructural morphology will be examined by electron microscopy, facilitated by a transgenic donor mouse with a reporter gene fused to a rhodopsin promotor; these transgenic rods uniquely express beta-galactosidase which allows their cytoplasm to be identified by electron microscopy. Photoreceptor function will be examined by the local ERG and trans-synaptic function by impulse recording and visually evoked cortical responses. A dye filled microelectrode will allow correlating responses with the transplant site in the retina.
| Gouras, Peter; Kong, Jian; Tsang, Stephen H (2002) Retinal degeneration and RPE transplantation in Rpe65(-/-) mice. Invest Ophthalmol Vis Sci 43:3307-11 |
| Ivert, Lena; Kjeldbye, Hild; Gouras, Peter (2002) Long-term effects of short-term retinal bleb detachments in rabbits. Graefes Arch Clin Exp Ophthalmol 240:232-7 |
| Ekesten, B; Gouras, P; Salchow, D J (2001) Ultraviolet and middle wavelength sensitive cone responses in the electroretinogram (ERG) of normal and Rpe65 -/- mice. Vision Res 41:2425-33 |
| Salchow, D J; Trokel, S L; Kjeldbye, H et al. (2001) Isolation of human fetal cones. Curr Eye Res 22:85-9 |
| Lai, C C; Gouras, P; Doi, K et al. (2000) Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer. Invest Ophthalmol Vis Sci 41:3134-41 |
| Ekesten, B; Gouras, P; Yamamoto, S (2000) Cone inputs to murine retinal ganglion cells. Vision Res 40:2573-7 |
| Lai, C C; Gouras, P; Doi, K et al. (1999) Tracking RPE transplants labeled by retroviral gene transfer with green fluorescent protein. Invest Ophthalmol Vis Sci 40:2141-6 |
| Sheng, Y; Gouras, P; Cao, H et al. (1995) Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. Invest Ophthalmol Vis Sci 36:381-90 |
| Perry, J; Du, J; Kjeldbye, H et al. (1995) The effects of bFGF on RCS rat eyes. Curr Eye Res 14:585-92 |
| Gouras, P; Cao, H; Sheng, Y et al. (1994) Patch culturing and transfer of human fetal retinal epithelium. Graefes Arch Clin Exp Ophthalmol 232:599-607 |
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