July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Transcriptional regulation of TL1A expression and its protection mechanism on pathological vascular permeability in nonproliferative diabetic retinopathy
Author Affiliations & Notes
  • Hua Yan
    Tianjin Medical University, Tianjin, China
  • Jianan Li
    Tianjin Medical University, Tianjin, China
  • Footnotes
    Commercial Relationships   Hua Yan, None; Jianan Li, None
  • Footnotes
    Support  National Natural Science Foundation of China (Grant Numbers 81830026, 8167086)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5363. doi:
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      Hua Yan, Jianan Li; Transcriptional regulation of TL1A expression and its protection mechanism on pathological vascular permeability in nonproliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5363.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Pathological vascular permeability participates the whole process of diabetic retinopathy (DR) and contributes to the progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). We sought a relationship between TL1A and pathological vascular permeability, illustrate transcriptional regulation of TL1A expression, and detect its protective effect and mechanism in NPDR.

Methods : In vitro experiments, pathological vascular permeability was confirmed by phosphorylation of VE-cadherin at Tyr685. TL1A gene expression was assessed by RT-qPCR and Western blot. We performed motif analysis to identify transcription factor binding sites and verified transcriptional regulation by ChIP-qPCR, luciferase assay, and small interfering RNA (siRNA). Transendothelial electrical resistance (TER), FITC-labeled dextran perfusion, and immunofluorescence (IF) were used to identify TL1A protection. In vivo experiments, after intravitreous injection of TL1A in normal or diabetic retinopathy models induced by streptozotocin, fluorescence angiography (FA) combining indocyanine green angiography (ICGA) was used to identify pathological degree and its improvement. Miles assay, IF and Evens blue staining were also used to proof protective effect. Co-immunoprecipitation was used to illustrate protection mechanism.

Results : Retinal microvascular endothelial cells were responsive to high glucose at 2 hours after stimulating, TL1A expression began to decrease in the meantime, and phosphorylation Tyr685 of VE-cadherin was increased at 8 hours. FOXP1 was the only one which can bind exactly and regulate TL1A expression. 250ng/mL TL1A could improve endothelial cells permeability and morphology of VE-cadherin. Overexpress or knock out TL1A by siRNA could delay or accelerate these pathological changes. Intravitreous injection of 0.5ng TL1A could improve pathological vascular permeability in DR models without side effects compared with the same dose of VEGF and IgG. Death receptor 3 could bind SHP-1 to dephosphorylation of VEGFR2 and decrease phosphorylation of VE-cadherin.

Conclusions : Decreasing of TL1A in the early stage may promote pathological vascular permeability. A low dose of TL1A could delay and anesis the progression of disease. These findings may lead to new approaches in clinical interventions or treatment target in NPDR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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