title: Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.
abstract: A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes. In theory, therefore, continuous intraocular administration of a normal form of a soluble lysosomal enzyme should be able to cure the molecular defect in the retinas of subjects lacking this enzyme. Experiments were conducted to determine whether genetically modified bone marrow-derived stem cells implanted into the vitreous could be used as -vehicles for continuous delivery of such enzymes to the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice were implanted into the vitreous of mice undergoing retinal degeneration as a result of a mutation in the PPT1 gene. The implanted cells appeared to survive indefinitely in the vitreous without proliferating or invading the retina. This indicates that intravitreal implantation of MSCs is likely a safe means of long-term delivery of proteins synthesized by the implanted cells. Experiments have been initiated to test the efficacy of using genetically modified autologous MSCs to inhibit retinal degeneration in a canine model of neuronal ceroid lipofuscinosis.
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, 65212, Columbia, MO, USA. cjtrvd@mail.missouri.edu.|Genetics Area Program, University of Missouri, Columbia, MO, 65211, USA. cjtrvd@mail.missouri.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Tracy
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, 65212, Columbia, MO, USA. douglas.n.sanders@gmail.com.|Department of Diagnostics Division, Novartis Pharmaceutical Inc., 02139, Cambridge, MA, USA. douglas.n.sanders@gmail.com.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Sanders
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri College of Veterinary Medicine, 65211, Columbia, MO, USA. bryanjn@missouri.edu.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bryan
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, 65212, Columbia, MO, USA. jensenc@health.missouri.edu.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Jensen
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, 65212, Columbia, MO, USA. castanerl@missouri.edu.
authors.forename: Leilani J
authors.initials: LJ
authors.lastname: Castaner
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, 65211, MO, USA. KirkM@missouri.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kirk
authors.affiliation: Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, 65212, Columbia, MO, USA. katzm@health.missouri.edu.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Katz
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D004285:Dogs; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D058449:Intravitreal Injections; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000628:therapy*; D014182:Transplantation, Autologous; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D049452:Green Fluorescent Proteins; D010447:Peptide Hydrolases
keywords: Autologous, therapy; Intravitreal implantation; Lysosomal storage disease; Mesenchymal stem cells; Retinal degeneration; Trophic effects