Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

Biji Mathew, Jacqueline N. Poston, John C. Dreixler, Leianne Torres, Jasmine Lopez, Ruth Zelkha, Irina Balyasnikova, Maciej S. Lesniak, Steven Roth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Purpose: Ischemia-associated retinal degeneration is one of the leading causes of vision loss, and to date, there are no effective treatment options. We hypothesized that delayed injection of bone-marrow stem cells (BMSCs) 24 h after the onset of ischemia could effectively rescue ischemic retina from its consequences, including apoptosis, inflammation, and increased vascular permeability, thereby preventing retinal cell loss. Methods: Retinal ischemia was induced in adult Wistar rats by increasing intraocular pressure (IOP) to 130–135 mmHg for 55 min. BMSCs harvested from rat femur were injected into the vitreous 24 h post-ischemia. Functional recovery was assessed 7 days later using electroretinography (ERG) measurements of the a-wave, b-wave, P2, scotopic threshold response (STR), and oscillatory potentials (OP). The retinal injury and anti-ischemic effects of BMSCs were quantitated by measuring apoptosis, autophagy, inflammatory markers, and retinal–blood barrier permeability. The distribution and fate of BMSC were qualitatively examined using real-time fundus imaging, and retinal flat mounts. Results: Intravitreal delivery of BMSCs significantly improved recovery of the ERG a- and b-waves, OP, negative STR, and P2, and attenuated apoptosis as evidenced by decreased TUNEL and caspase-3 protein levels. BMSCs significantly increased autophagy, decreased inflammatory mediators (TNF-α, IL-1β, IL-6), and diminished retinal vascular permeability. BMSCs persisted in the vitreous and were also found within ischemic retina. Conclusions: Taken together, our results indicate that intravitreal injection of BMSCs rescued the retina from ischemic damage in a rat model. The mechanisms include suppression of apoptosis, attenuation of inflammation and vascular permeability, and preservation of autophagy.

Original languageEnglish (US)
Pages (from-to)1581-1592
Number of pages12
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume255
Issue number8
DOIs
StatePublished - Aug 1 2017

Keywords

  • Apoptosis
  • Autophagy
  • Bone-marrow mesenchymal stem cells
  • Electroretinography
  • Inflammation
  • Ischemia
  • Retinal vascular permeability

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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