Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns

Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3513-3518. doi: 10.1167/iovs.17-21810.


Purpose: Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment.

Methods: Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified.

Results: AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins.

Conclusions: Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkalies
  • Amnion / drug effects*
  • Amnion / transplantation*
  • Animals
  • Burns, Chemical / metabolism
  • Burns, Chemical / surgery*
  • Corneal Ulcer / metabolism
  • Corneal Ulcer / surgery*
  • Disease Models, Animal
  • Eye Burns / chemically induced*
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Keratolytic Agents / pharmacology*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Tissue Engineering
  • Transplants
  • Tretinoin / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / physiology


  • Alkalies
  • Keratolytic Agents
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Tretinoin
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse