Intravitreal injection of mesenchymal stem cells evokes retinal vascular damage in rats

FASEB J. 2019 Dec;33(12):14668-14679. doi: 10.1096/fj.201901500R. Epub 2019 Nov 5.

Abstract

The aim of this study is to investigate the vascular outcome after intravitreal mesenchymal stem cell (MSC) administration in rats without or with damage to the neurovascular unit [transgenic (TGR) rats]. Male Sprague-Dawley (SD) and TGR rats received an intravitreal injection of 2 × 104 rat bone marrow-derived MSCs (BMSCs) or human adipose-derived stem cells (ASCs) at postnatal d 30. After 4 wk, vasculature, neuronal function, and gene expression in the retinas were evaluated using retinal morphometry, electroretinography, immunofluorescence, Western blot, and quantitative PCR. Intravitreal administration of rat BMSCs and human ASCs in both SD and TGR eyes induced cataract, loss of pericytes, and increased formation of acellular capillaries. BMSCs remained in the vitreous cavity and did not migrate into the retinas. Intravitreal administration of BMSCs impacted retinal neuronal function in neither SD nor TGR rats. Retinal glial activation, elevation of IL-1β, C3, arginase 1, and heat shock protein 90 were detected in BMSC-injected SD rats. Intravitreal administration of MSCs induces cataract, retinal vasoregression, activation of retinal glial cells, and inflammatory response in rat eyes.-Huang, H., Kolibabka, M., Eshwaran, R., Chatterjee, A., Schlotterer, A., Willer, H., Bieback, K., Hammes, H.-P., Feng, Y. Intravitreal injection of mesenchymal stem cells evokes retinal vascular damage in rats.

Keywords: inflammation; retina; vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Arginase / metabolism
  • Cataract / etiology*
  • Cataract / pathology
  • Cell Movement
  • Cells, Cultured
  • HSP90 Heat-Shock Proteins / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation / adverse effects*
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Pericytes / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*

Substances

  • HSP90 Heat-Shock Proteins
  • Interleukin-1beta
  • Arginase