Pigment epithelial cell of the eye, its production and use in therapy of an eye or CNS disease

Abstract

The present invention relates to a pigment epithelial cell of the eye containing vector DNA of an adenoviral vector with large DNA capacity, to the improved isolation and cultivation of these cells and to methods for production and the use in the therapy of an eye or nerve disease.

1 . A pigment epithelial cell of the eye, which comprises vector DNA of an adenoviral vector with large DNA capacity comprising at least one expressed nucleic acid operatively linked to a promoter.  
   
   
       2 . The pigment epithelial cell of the eye as claimed in  claim 1 , which is a retinal pigment epithelial cell or an iris pigment epithelial cell.  
   
   
       3 . The pigment epithelial cell of the eye as claimed in  claim 1 , where the vector DNA comprises at least one therapeutic nucleic acid, in particular a therapeutic gene, preferably for a neurotrophic factor such as GDNF, PEDF, NGF, BDNF, CNTF, bFGF or neurotrophin 3,4-5, an antiangiogenetic factor such as a soluble VEGF receptor-1 (sflt-1), a dominant-negative VEGF receptor-2 (KDR) or PEDF, an antioxidative factor such as superoxide dismutase, catalase or various peroxydases, a lysosomal factor such as alpha-mannosidase, beta-galactosidase, N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, and lipase, or a vasodilating factor such as NO synthase.  
   
   
       4 . The pigment epithelial cell of the eye as claimed in  claim 1 , where the vector DNA comprises any one or more of a constitutively active, a regulatable or a tissue-specific promoter, or a regulatable expression system.  
   
   
       5 . The pigment epithelial cell of the eye as claimed in  claim 1 , where the cell produces at least one therapeutic protein.  
   
   
       6 . The pigment epithelial cell as claimed in  claim 1 , where the cell is in a fixed assemblage of cells.  
   
   
       7 . A pigment epithelial cell of the eye in the form of a fixed assemblage of cells.  
   
   
       8 . A cultivation system comprising at least one pigment epithelial cell of the eye and a feeder layer.  
   
   
       9 . A method for producing a pigment epithelial cell of the eye as claimed in  claim 1 , which comprises genetically modifying the cell with the aid of an adenoviral vector with large DNA capacity.  
   
   
       10 . A method for producing a pigment epithelial cell of the eye as claimed in  claim 1 , which comprises cultivating the cell in serum-free medium or in the presence of a feeder layer.  
   
   
       11 . A method for producing pigment epithelial cells of the eye in the form of a fixed assemblage of cells as claimed in  claim 7 , which comprises separating the assemblage of cells, in particular enzymatically, from surrounding tissue.  
   
   
       12 . A method for producing pigment epithelial cells, which comprises cultivating the cells in a cultivation system as claimed in  claim 8 .  
   
   
       13 . A method of treating an eye disease, in particular of AMD, a glaucoma, diabetic retinopathy or a genetic disease of the pigment epithelium, which comprises using a pigment epithelial cell as claimed in  claim 1 .  
   
   
       14 . A method of treating an eye disease, in particular of AMD, a glaucoma, diabetic retinopathy or a genetic disease of the pigment epithelium, which comprises using a pigment epithelial cell as claimed in  claim 7 .  
   
   
       15 . A method of treating as claimed in  claim 13  or 14, where the pigment epithelial cell is transplanted into the eye, in particular the choroid, into the papilla and/or into the vitreous.  
   
   
       16 . A method of treating a nerve disease, in particular a disease of the nervous system, preferably of the CNS, especially of Parkinson's disease, which comprises using a pigment epithelial cell.  
   
   
       17 . The method of treating as claimed in  claim 16 , wherein the pigment epithelial cell is a pigment epithelial cell as claimed in  claim 1 .  
   
   
       18 . The method of treating as claimed in  claim 16 , wherein the pigment epithelial cell is transplanted into the nervous system, in particular the CNS.  
   
   
       19 . The method of treating as claimed in  claim 13  or  14 , wherein the pigment epithelial cell is an autologous pigment epithelial cell.  
   
   
       20 . The method of treating as claimed in  claim 16 , wherein the pigment epithelial cell is an autologous pigment epithelial cell.  
   
   
       21 . A medicament or diagnostic aid comprising a pigment epithelial cell of the eye as claimed in  claim 1  and other excipients or additives.  
   
   
       22 . The pigment epithelial cell of the eye as claimed in  claim 1 , where the cell produces at least one therapeutic RNA.  
   
   
       23 . The pigment epithelial cell as claimed in  claim 1 , where the cell has been cultivated in the presence of a feeder layer.  
   
   
       24 . The pigment epithelial cell as claimed in  claim 1 , where the cell has been cultivated in serum-free medium.