title: Age-dependent differences in recovered visual responses in Royal College of Surgeons rats transduced with the Channelrhodopsin-2 gene.
abstract: The objective of this study is to investigate age-related differences in recovered visual function in Royal College of Surgeons (RCS) rats transduced with the Channelrhodopsin-2 (ChR2) gene. An adeno-associated virus vector that contained ChR2 was injected intravitreously into young or aged RCS rats. After 4 months, visual evoked potentials were recorded. To estimate the transduction efficiencies, ChR2V-expressing cells and retrograde labeled retinal ganglion cells (RGCs) were counted. After photoreceptor degradation, immunohistochemistry was used to detect glial fibrillary acidic protein (GFAP) in the retinas. The amplitudes and latencies from young RCS rats were higher and shorter, respectively, than those from aged RCS rats. ChR2V was expressed in the RGCs of both groups of rats; there was no significant difference in the transduction efficiency of either group. However, the number of RGCs in aged RCS rats was significantly less than that in young RCS rats. In addition, strong GFAP immunoreactivity was observed after photoreceptor degeneration, whereas it was weaker in ChR2V-expressing RGCs. ChR2 transduction produced photosensitive RGCs in both young and aged rats. However, the degree of recovery depended on the age at the time of transduction.
authors.affiliation: Institute for International Advanced Interdisciplinary Research, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Isago
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugano
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Namie
authors.initials: N
authors.lastname: Murayama
authors.forename: Eri
authors.initials: E
authors.lastname: Koyanagi
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomita
mesh_terms: D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D005074:Evoked Potentials, Visual; D005136:Eye Proteins / Q000032:analysis; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D023421:Models, Animal; D009410:Nerve Degeneration / Q000473:pathology* / Q000517:prevention & control; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D011930:Reaction Time; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D058499:Retinal Dystrophies / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D014161:Transduction, Genetic; D000076202:c-Mer Tyrosine Kinase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C523009:channelopsin-2, Chlamydomonas reinhardtii; C490765:Mertk protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase