title: Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina.
abstract: To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.
authors.affiliation: Biochemistry Doctoral Program, The Graduate School, City University of New York, New York, NY, USA.|Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.
authors.forename: Uchenna John
authors.initials: UJ
authors.lastname: Unachukwu
authors.affiliation: Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Warren
authors.affiliation: Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, City College of New York, City University of New York, NY, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.|Neuroscience Doctoral Program, The Graduate School, City University of New York, New York, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.
authors.forename: Moira
authors.initials: M
authors.lastname: Sauane
authors.affiliation: Departments of Physics and Biology, Hunter College of the City University of New York, New York, NY USA.
authors.forename: Hyungsik
authors.initials: H
authors.lastname: Lim
authors.affiliation: Department of Biomedical Engineering, City College of New York, City University of New York, NY, USA.
authors.forename: Maribel
authors.initials: M
authors.lastname: Vazquez
authors.affiliation: Biochemistry Doctoral Program, The Graduate School, City University of New York, New York, NY, USA.|Department of Biological Sciences, Lehman College, City University of New York, Bronx, NY, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Redenti
mesh_terms: D002465:Cell Movement; D005136:Eye Proteins / Q000096:biosynthesis*; D006801:Humans; D008954:Models, Biological; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000637:transplantation; D012164:Retinal Diseases / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction
chemical_list: D005136:Eye Proteins