title: Alteration of Neurotrophic Factors After Transplantation of Bone Marrow Derived Lin-ve Stem Cell in NMDA-Induced Mouse Model of Retinal Degeneration.
abstract: Retinal ganglion cell layer (RGCs) is one of the important layers of retina, depleted in Glaucoma. Loss of RGC neurons is a major cellular mechanism involved in its pathogenesis resulting in severe vision loss. Stem cell therapy has emerged as a potential strategy to arrest the apoptotic loss of RGCs and also replace the degenerative cells in damaged retina. Here, we have investigated the incorporation and survival of mouse bone marrow derived Lin-ve stem cells in N-methyl-d-aspartate (NMDA)-induced mouse model of retinal degeneration. Two days after intravitreal injection of NMDA (100 mM) showed significant decrease in ganglion cell number and increase in TUNEL positive apoptotic cells in retinal layers. The injury was further characterized by immunohistochemical expression of Brn3b, GFAP, Bcl2, pCREB, CNTF, GDNF, and BDNF in retinal layers. Lin-ve cells (100,000 dose) were intravitreally transplanted after 2 days of injury and evaluated after 7, 14, and 21 days of transplantation. Transplanted cells were found to have migrated from intravitreal space and incorporated into injured retina at 7, 14, and 21 days post-transplantation. At 21 days Brn3b, CNTF, and BDNF expression was found to be upregulated whereas GDNF was downregulated when compared to respective injury time points. Molecular data showed decrease in the expression of Brn3b, BDNF, CNTF, and GDNF post transplantation when compared with injury groups. This study reveals that Lin-ve stem cells may exert neuroprotective effect in damaged retina mediated by participation of neurotrophic factors induced by stem cell transplantation at the site of injury. J. Cell. Biochem. 118: 1699-1711, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Neuroscience Research Lab, Department of Neurology, PGIMER, Chandigarh 160012, India.
authors.forename: Neeru
authors.initials: N
authors.lastname: Jindal
authors.affiliation: Neuroscience Research Lab, Department of Neurology, PGIMER, Chandigarh 160012, India.
authors.forename: Avijit
authors.initials: A
authors.lastname: Banik
authors.affiliation: Neuroscience Research Lab, Department of Neurology, PGIMER, Chandigarh 160012, India.
authors.forename: Sudesh
authors.initials: S
authors.lastname: Prabhakar
authors.affiliation: Department of Histopathology, PGIMER, Chandigarh 160012, India.
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphie
authors.affiliation: Neuroscience Research Lab, Department of Neurology, PGIMER, Chandigarh 160012, India.
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000633:toxicity*; D009414:Nerve Growth Factors / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D050820:Transcription Factor Brn-3B / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; C085559:Pou4f2 protein, mouse; D050820:Transcription Factor Brn-3B; D016202:N-Methylaspartate
keywords: BDNF; BONE MARROW; CNTF; LIN-VE; NMDA; STEM CELL