Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy

Mol Med Rep. 2017 Feb;15(2):573-580. doi: 10.3892/mmr.2016.6048. Epub 2016 Dec 14.

Abstract

Tumor necrosis factor (TNF) ligand related molecule 1A (TL1A), also termed TNF superfamily member 15 and vascular endothelial growth inhibitor is important for tumorigenicity and autoimmunity. However, the function of TL1A in diabetic retinopathy (DR) remains to be elucidated. The present study established a diabetes mellitus (DM) rat model to investigate TL1A, vascular endothelial growth factor (VEGF), tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) expression levels in the retina, vitreous and serum of rats with DM at different stages (1 month group, 3 month group and 6 month group). The present study determined that TL1A expression levels in the retina and vitreous from the DM 1 month group were significantly lower compared with the control group. However, TL1A levels in the retina and vitreous were significantly increased in advanced stages of DM compared with the control group. Furthermore, the levels of VEGF in the retina and vitreous were significantly higher in the DM groups compared with the control group. The expression levels of TNF‑α and IL‑1β in the retina and vitreous were significantly higher in DM 3 month and 6 month groups compared with the control group. It is of note that the expression levels of TL1A were significantly lower in the DM 1 and 3 month groups compared with the control group; however, they were significantly increased in the DM 6 month group compared with the DM 3 month group. The expression levels of VEGF, TNF‑α and IL‑1β in blood serum have been observed to exhibit similar expression change dynamics as those of the retina and vitreous. Therefore, these findings suggest that TL1A may be a protective factor of DR, and may provide a rationale for the development of novel therapeutic strategies to treat DR.

MeSH terms

  • Animals
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Interleukin-1beta / blood*
  • Male
  • Rats
  • Rats, Wistar
  • Retina / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / blood
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism*
  • Tumor Necrosis Factor-alpha / blood*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Interleukin-1beta
  • Tnfsf15 protein, rat
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A