Deletion of toll-like receptor 4 ameliorates diabetic retinopathy in mice

Arch Physiol Biochem. 2023 Apr;129(2):519-525. doi: 10.1080/13813455.2020.1841795. Epub 2020 Nov 6.

Abstract

Background: Diabetic retinopathy is a common and specific microvascular complication of diabetes, which is also the leading cause of preventable blindness. Therefore, we aimed to find a promising therapeutic strategy for diabetic retinopathy.

Methods: To investigate the role of toll-like receptor 4 (TLR4) in the diabetic retinopathy, we injected streptozotocin (STZ) into wild-type (wt) and TLR4 knock-out mice to induce diabetes.

Results: While STZ induced diabetes both in wt and TLR4-/- mice, deletion of TLR4 in diabetic mice significantly improved diabetic retinopathy compared to diabetic wt mice, as judged by the enhanced thickness of retinal tissue. Furthermore, TLR4-dependent NF-κB pathway, inflammatory cytokine release and the expressions of vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP), which were all remarkably stimulated in STZ-injected wt mice, were inhibited in STZ-injected TLR4-/- mice.

Conclusion: TLR4 could serve as an independent target for treating diabetic retinopathy.

Keywords: TLR4; diabetes; mice; retinopathy; therapy.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Retinopathy* / genetics
  • Mice
  • Retina / metabolism
  • Toll-Like Receptor 4 / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Toll-Like Receptor 4
  • Vascular Endothelial Growth Factor A