The effect of biodegradable silk fibroin-based scaffolds containing glial cell line-derived neurotrophic factor (GDNF) on the corneal regeneration process

Int J Biol Macromol. 2021 Aug 31:185:264-276. doi: 10.1016/j.ijbiomac.2021.06.040. Epub 2021 Jun 10.

Abstract

Corneal injury due to ocular trauma or infection is one of the most challenging vision impairing pathologies. The aim of the work was to study the effect of biodegradable silk fibroin-based scaffolds containing GDNF on the corneal regeneration process. During cultivate the highest keratocytes proliferative activity was registered with scaffolds containing 250 ng/ml and 500 ng/ml GDNF. In mice with an experimental model of epithelial-stromal damage to the cornea, silk fibroin-based scaffolds containing GDNF in various concentrations were used (in groups 1, 2 and 3 silk fibroin-based scaffolds containing GDNF in a concentration of 50 ng/ml, 250 ng/ml and 500 ng/ml, respectively; in group 4 - silk fibroin-based scaffolds without GDNF; in group 5 - a solution of GDNF with concentration of 500 ng/ml; group 6- control). The area of the corneal epithelial defect in groups 2, 3, and 5 was less than in the other groups. The most pronounced positive immunohistochemical reaction with antibodies to Bcl2, Bax, phosphoERK1/2 and phospho-JNK1/2, Ki67, Gap43 was observed in groups 2 and 3. Thus, silk fibroin-based scaffolds with GDNF stimulate the epithelialization process, proliferative activity of epithelial cells and keratocytes, accelerate the formation of the stromal nerve plexus and exhibit anti-apoptotic activity.

Keywords: Epithelial-stromal damage to the cornea; Glial neurotrophic factor; Silk fibroin.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Proliferation
  • Corneal Injuries / metabolism
  • Corneal Injuries / therapy*
  • Fibroins / chemistry*
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Keratinocytes / transplantation*
  • Male
  • Mice
  • Primary Cell Culture
  • Tissue Scaffolds

Substances

  • Biomarkers
  • Glial Cell Line-Derived Neurotrophic Factor
  • Fibroins