title: Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model.
abstract: OBJECTIVE
  The purpose of this study was to investigate the neuroprotective effects of bone marrow bone marrow-derived and adipose tissue-derived mesenchymal stromal cells (MSCs) that were intravitreally transplanted in an experimental ocular hypertension (OHT) model.
  
  
  METHODS
  An OHT rat model was generated by means of intracameral injection of hyaluronic acid into the anterior chamber. MSCs labeled with green fluorescence protein were transplanted intravitreally 1 week after OHT induction. At the end of the second and fourth weeks, retinal ganglion cells were visualized with the use of a flat-mount retina method and were evaluated by means of immunofluorescence staining against green fluorescence protein, vimentin, CD105, and cytokines (interleukin [IL]-1Ra, prostaglandin E2 receptor, IL-6, transforming growth factor-β1, interferon-γ and tumor necrosis factor-α).
  
  
  RESULTS
  The retinal ganglion cell numbers per area were significantly improved in stem cell-treated OHT groups compared with that in the non-treated OHT group (P < 0.05). The results of immunohistochemical analyses indicated that a limited number of stem cells had integrated into the ganglion cell layer and the inner nuclear layer. The number of cells expressing proinflammatory cytokines (interferon-γ and tumor necrosis factor-α) decreased in the MSC-transferred group compared with that in the OHT group after 4 weeks (P < 0.01). On the other hand, IL-1Ra and prostaglandin E2 receptor expressions were increased in the rat bone marrow-derived MSC group but were more significant in the rat adipose tissue-derived MSC group (P < 0.01).
  
  
  CONCLUSIONS
  After intravitreal transplantation, MSCs showed a neuroprotective effect in the rat OHT model. Therefore, MSCs promise an alternative therapy approach for functional recovery in the treatment of glaucoma.
authors.affiliation: Department of Ophthalmology, Çerkezköy State Hospital, Tekirdağ, Turkey. Electronic address: esra_degr@hotmail.com.
authors.forename: Esra
authors.initials: E
authors.lastname: Emre
authors.affiliation: Department of Ophthalmology, School of Medicine, Kocaeli University, Kocaeli, Turkey.
authors.forename: Nurşen
authors.initials: N
authors.lastname: Yüksel
authors.affiliation: Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Duruksu
authors.affiliation: Department of Ophthalmology, School of Medicine, Kocaeli University, Kocaeli, Turkey.
authors.forename: Dilara
authors.initials: D
authors.lastname: Pirhan
authors.affiliation: Liv Hospital, Center for Regenerative Medicine and Stem Cell Research & Manufacturing (Liv MedCell) Istanbul, Turkey.
authors.forename: Cansu
authors.initials: C
authors.lastname: Subaşi
authors.affiliation: Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.
authors.forename: Gülay
authors.initials: G
authors.lastname: Erman
authors.affiliation: Liv Hospital, Center for Regenerative Medicine and Stem Cell Research & Manufacturing (Liv MedCell) Istanbul, Turkey.
authors.forename: Erdal
authors.initials: E
authors.lastname: Karaöz
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D058449:Intravitreal Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D049452:Green Fluorescent Proteins
keywords: cytokines; mesenchymal stromal cells; neuroprotection; ocular hypertension; retinal ganglion cells