Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model

Cytotherapy. 2015 May;17(5):543-59. doi: 10.1016/j.jcyt.2014.12.005. Epub 2015 Jan 22.

Abstract

Background aims: 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.

Keywords: cytokines; mesenchymal stromal cells; neuroprotection; ocular hypertension; retinal ganglion cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Separation
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • Intraocular Pressure / drug effects
  • Intravitreal Injections
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Ocular Hypertension / drug therapy
  • Ocular Hypertension / physiopathology
  • Ocular Hypertension / therapy*
  • Rats, Wistar
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / pathology

Substances

  • Cytokines
  • Neuroprotective Agents
  • Green Fluorescent Proteins