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 journalArticle

12 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 ; 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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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; 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

TY - JOUR

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

AU - Lesniak, Maciej S.

AU - Roth, Steven

PY - 2017/8/1

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AB - 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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KW - Autophagy

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KW - Electroretinography

KW - Inflammation

KW - Ischemia

KW - Retinal vascular permeability

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