Retinal Pigment Epithelial Stem Cells

Abstract

The present invention relates to a retinal pigment epithelial stem cell isolated from a posterior region of the retinal pigment epithelium of an adult mammal. The invention also relates to a method of inducing differentiation of retinal epithelial stem and progenitor cells in vitro, wherein the cells of the invention are highly plastic, multipotential stem cells. The invention also includes methods for the treatment of retinal diseases and vision loss involving the transplantation of retinal pigment epithelial stem cells or cells differentiated from retinal pigment epithelial stern cells to the retina of a patient in need of treatment.

1 .- 47 . (canceled) 
     
     
         48 . A method for treating a retinal disease or disorder, selected from a group consisting of macular degeneration, age-related macular degeneration, retinitis pigmentosa, Leber's hereditary optic neuropathy and cone dystrophy, which method comprises activating retinal pigment epithelial stem cells (RPESCs) in situ to obtain retinal pigment eipthelial progeny cells, by administration to the eye of a subject of one or more factors suitable to stimulate proliferation of endogenous RPESCs of the subject 
     
     
         49 . The method of  claim 48 , wherein the one or more factors include one or more growth factors selected from the group consisting of nerve growth factor, glial cell-line derived growth factor, neurotropin 3, neurotropin 4/5, neurotropin 6, ciliary neurotropic factor, interleukin 6, interleukin 11, cardiotropin 1, a growth factor hormone, hyaluronidase, chondroitinase ABC, fibroblast growth factor 2 (FGF2), epidermal growth factor and sonic hedgehog. 
     
     
         50 . The method of  claim 49 , wherein the one or more factors include at least FGF2. 
     
     
         51 . The method of  claim 48 , wherein said administration provides sustained delivery of said one or more factors to the eye. 
     
     
         52 . The method of  claim 51 , wherein said sustained delivery is provided by incorporating the one or more factors in a delivery vehicle selected from the group consisting of a polymer matrix, microspheres and liposomes and combinations thereof. 
     
     
         53 . The method of  claim 52 , wherein the polymer matrix is poly(lactide-co-glycolide) (PLGA). 
     
     
         54 . The method of  claim 52 , wherein the microspheres comprises PLGA and polyvinyl alcohol. 
     
     
         55 . The method of  claim 54 , wherein the microspheres are suspended in alginate hydrogel. 
     
     
         56 . The method of  claim 51 , wherein said microspheres have a diameter of between 10 and 40μ. 
     
     
         57 . The method of  claim 56 , wherein said microspheres have an average diameter of 20μ. 
     
     
         58 . The method of  claim 48 , wherein said administration is by intraocular injection. 
     
     
         59 . The method of  claim 48 , wherein the retinal disease or disorder is macular degeneration or retinitis pigmentosa. 
     
     
         60 . The method of  claim 48 , wherein the retinal disease or disorder is age-related macular degeneration. 
     
     
         61 . The method of  claim 51 , wherein each delivery vehicle contains a single factor. 
     
     
         62 . The method of  claim 51 , wherein each delivery vehicles contains more than one factor. 
     
     
         63 . The method of  claim 61 , wherein two or more delivery vehicles are administered in combination. 
     
     
         64 . The method of  claim 51 , wherein said factor is provided at a concentration of from 1 ng/ml to 20 ng/ml of delivery vehicle. 
     
     
         65 . The method of  claim 64 , wherein upon administration to the eye said delivery vehicle releases about 5 ng/ml over a course of at least 7 days.