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 V Balyasnikova, Maciej S Lesniak, Steven Roth*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

Mesenchymal Stromal Cells
Bone Marrow Cells
Stem Cells
Ischemia
Bone Marrow
Autophagy
Capillary Permeability
Electroretinography
Retina
Apoptosis
Inflammation
Retinal Vessels
Retinal Degeneration
Intravitreal Injections
In Situ Nick-End Labeling
Intraocular Pressure
Interleukin-1
Evoked Potentials
Caspase 3
Femur

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

Cite this

Mathew, Biji ; Poston, Jacqueline N. ; Dreixler, John C. ; Torres, Leianne ; Lopez, Jasmine ; Zelkha, Ruth ; Balyasnikova, Irina V ; Lesniak, Maciej S ; Roth, Steven. / Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats. In: Graefe's Archive for Clinical and Experimental Ophthalmology. 2017 ; Vol. 255, No. 8. pp. 1581-1592.
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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.",
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Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats. / Mathew, Biji; Poston, Jacqueline N.; Dreixler, John C.; Torres, Leianne; Lopez, Jasmine; Zelkha, Ruth; Balyasnikova, Irina V; Lesniak, Maciej S; Roth, Steven.

In: Graefe's Archive for Clinical and Experimental Ophthalmology, Vol. 255, No. 8, 01.08.2017, p. 1581-1592.

Research output: Contribution to journalArticle

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T1 - Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

AU - Mathew, Biji

AU - Poston, Jacqueline N.

AU - Dreixler, John C.

AU - Torres, Leianne

AU - Lopez, Jasmine

AU - Zelkha, Ruth

AU - Balyasnikova, Irina V

AU - Lesniak, Maciej S

AU - Roth, Steven

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