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

Graefes Arch Clin Exp Ophthalmol. 2017 Aug;255(8):1581-1592. doi: 10.1007/s00417-017-3690-1. Epub 2017 May 18.


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.

Keywords: Apoptosis; Autophagy; Bone-marrow mesenchymal stem cells; Electroretinography; Inflammation; Ischemia; Retinal vascular permeability.

MeSH terms

  • Animals
  • Apoptosis
  • Blood-Retinal Barrier
  • Bone Marrow Cells / cytology*
  • Capillary Permeability
  • Disease Models, Animal
  • Electroretinography
  • In Situ Nick-End Labeling
  • Intravitreal Injections
  • Ischemia / diagnosis
  • Ischemia / metabolism
  • Ischemia / therapy*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Rats
  • Rats, Wistar
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / therapy*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*
  • Retinal Vessels / physiopathology