|Functional analyses of TNFR2 in physiological and pathological retina angiogenesis.|
|PMID: 23188724 Owner: NLM Status: MEDLINE|
|PURPOSE: To determine the function of tumor necrosis factor receptor-2 (TNFR2) in retinal development and ischemia-induced revascularization in an oxygen-induced retinopathy (OIR) model.
METHODS: Mice with a global deletion of TNFR2 (TNFR2-KO) or with a vascular endothelial cell (EC)-specific TNFR2 transgene (TNFR2-TG) were compared to wild-type C57BL/6 mice (WT). Retinal vasculature development was visualized by whole-mount and cross-sectional isolectin staining. In the OIR model, neonatal mice were subjected to 75% oxygen from postnatal day (P)7 to P12 and then returned to normoxia from P12 to P17. Immunostaining and biochemical analyses were performed to assess the effects of TNFR2 deletion and TNFR2 transgenesis on retinal vascular repair.
RESULTS: TNFR2 deletion slightly delayed, while TNFR2 transgenesis weakly promoted, intraretinal vascular development and intraretinal vessel growth. TNFR2 deletion enhanced, while TNFR2 transgene reduced, hyperoxia-induced vaso-obliteration. However, hypoxia-induced revascularization and development of deep intraretinal vessels at P17 were reduced in TNFR2-KO but increased in TNFR2-TG mice without significant increase in preretinal neovascularization (NV). Moreover, TNFR2-TG/KO mice in which only vascular EC express TNFR2 sufficiently rescued the vascular defects of TNFR2-KO in the OIR model. Biochemical analyses of retina tissues showed that the phenotypic changes in retina correlated with TNFR2-dependent activation of Nuclear factor-κB (NF-κB) survival and bone marrow kinase (Bmx)-VEGFR2 angiogenic pathways.
CONCLUSIONS: TNFR2 plays a marginal role during retinal vascular development. TNFR2 in vascular EC strongly prevents hyperoxia-induced vaso-obliteration by inhibiting cell apoptosis, and promotes retinal repair by enhancing hypoxia-induced revascularization without increasing pathological neovascular tufts. Therefore, activation of TNFR2 signaling may be an ideal strategy for the treatment of OIR.
|Ting Wan; Zhe Xu; Huanjiao Jenny Zhou; Haifeng Zhang; Yan Luo; Yonghao Li; Wang Min|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-09|
|Title: Investigative ophthalmology & visual science Volume: 54 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2013 Jan|
|Created Date: 2013-01-10 Completed Date: 2013-03-12 Revised Date: 2014-04-22|
Medline Journal Info:
|Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States|
|Languages: eng Pagination: 211-21 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Anoxia / metabolism
Disease Models, Animal
Endothelium, Vascular / metabolism
Epithelial Cells / cytology, metabolism
Mice, Inbred C57BL
NF-kappa B / metabolism
Oxygen / adverse effects
Protein-Tyrosine Kinases / genetics
Receptor, TIE-2 / genetics
Receptors, Tumor Necrosis Factor, Type II / deficiency, genetics, metabolism*
Retina / pathology
Retinal Neovascularization / metabolism*
Retinopathy of Prematurity / metabolism*
Vascular Endothelial Growth Factor Receptor-2 / metabolism
|R0 HL085789/HL/NHLBI NIH HHS; R01 HL109420/HL/NHLBI NIH HHS; R01 HL115148/HL/NHLBI NIH HHS; R01HL065978/HL/NHLBI NIH HHS; R01HL109420/HL/NHLBI NIH HHS|
|0/Angiopoietin-2; 0/NF-kappa B; 0/Receptors, Tumor Necrosis Factor, Type II; EC 2.7.1.-/Bmx protein, mouse; EC 184.108.40.206/Protein-Tyrosine Kinases; EC 220.127.116.11/Receptor, TIE-2; EC 18.104.22.168/Vascular Endothelial Growth Factor Receptor-2; S88TT14065/Oxygen|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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