title: Autologous transplantation of genetically modified iris pigment epithelial cells: a promising concept for the treatment of age-related macular degeneration and other disorders of the eye.
abstract: Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.
authors.affiliation: Center for Molecular Medicine Cologne (ZMMK), Center of Ophthalmology, Department of Retinal Surgery, Institute for Anatomy, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Semkova
authors.forename: Florian
authors.initials: F
authors.lastname: Kreppel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Welsandt
authors.forename: Thomas
authors.initials: T
authors.lastname: Luther
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kozlowski
authors.forename: Hanna
authors.initials: H
authors.lastname: Janicki
authors.forename: Stefan
authors.initials: S
authors.lastname: Kochanek
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000375:Aging; D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D005128:Eye Diseases / Q000628:therapy*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D007498:Iris / Q000166:cytology* / Q000378:metabolism*; D007834:Lasers; D008164:Luminescent Proteins / Q000378:metabolism; D008268:Macular Degeneration / Q000628:therapy*; D008856:Microscopy, Fluorescence; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000628:therapy; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins