Tags

Type your tag names separated by a space and hit enter

Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization.
Invest Ophthalmol Vis Sci. 2010 Aug; 51(8):3874-83.IO

Abstract

PURPOSE

Tumor necrosis factor alpha (TNF)-alpha contributes to inflammation-associated angiogenesis. This study investigates the role of TNF-alpha receptors 1a and 1b in the development of choroidal neovascularization (CNV).

METHODS

CNV was induced in Tnfrsf1a(-/-) and Tnfrsf1b(-/-) mice with C57Bl6/J background and their wild-type (WT) (C57Bl/6J) controls by laser damage to the Bruch's membrane. TNF-alpha expression in RPE/choroid was determined by Western blot analysis. Pathologic angiogenesis was estimated qualitatively and quantitatively by fluorescein angiography and histology on choroidal flat mounts and paraffin cross-sections. Inflammatory cell invasion was investigated by clodronic acid depletion of circulating macrophages and immunochemistry, and the apoptotic activity was investigated by TUNEL assay and by caspase-3 and caspase-8 expression. Receptor 1b-specific Bmx/Etk kinase was detected by immunochemistry.

RESULTS

TNF-alpha levels were elevated after laser treatment. Severe CNV lesions and increased macrophage invasion were observed in Tnfrsf1a(-/-) compared with WT and Tnfrsf1b(-/-) mice. Increased immunoreactivity for Bmx/Etk kinase corresponded to the severity of CNV formation. Reduced pathologic angiogenesis and macrophage invasion in Tnfrsf1b(-/-) mice (vs. WT and Tnfrsf1a(-/-)) was accompanied by enhanced endothelial cell apoptosis and by caspase-3 and caspase-8 activation.

CONCLUSIONS

Receptor 1b promotes the recruitment of inflammatory cells to the site of injury and exacerbated pathologic angiogenesis probably by way of the Bmx/Etk-kinase-dependent pathway in the absence of receptor 1a. On the other hand, receptor 1a-dependent apoptosis in the absence of receptor 1b leads to reduced inflammatory response and CNV lesions after laser treatment. This demonstrates the potential for specific targeting of TNF-alpha receptors for future therapies of inflammation-associated choroidal neovascularization.

Authors+Show Affiliations

Department of Ophthalmology, Heinrich-Heine University, Düsseldorf, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20335614

Citation

Jasielska, Monika, et al. "Differential Role of Tumor Necrosis Factor (TNF)-alpha Receptors in the Development of Choroidal Neovascularization." Investigative Ophthalmology & Visual Science, vol. 51, no. 8, 2010, pp. 3874-83.
Jasielska M, Semkova I, Shi X, et al. Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2010;51(8):3874-83.
Jasielska, M., Semkova, I., Shi, X., Schmidt, K., Karagiannis, D., Kokkinou, D., Mackiewicz, J., Kociok, N., & Joussen, A. M. (2010). Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization. Investigative Ophthalmology & Visual Science, 51(8), 3874-83. https://doi.org/10.1167/iovs.09-5003
Jasielska M, et al. Differential Role of Tumor Necrosis Factor (TNF)-alpha Receptors in the Development of Choroidal Neovascularization. Invest Ophthalmol Vis Sci. 2010;51(8):3874-83. PubMed PMID: 20335614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization. AU - Jasielska,Monika, AU - Semkova,Irina, AU - Shi,Xuan, AU - Schmidt,Kristina, AU - Karagiannis,Dimitrios, AU - Kokkinou,Despina, AU - Mackiewicz,Jerzy, AU - Kociok,Norbert, AU - Joussen,Antonia M, Y1 - 2010/03/24/ PY - 2010/3/26/entrez PY - 2010/3/26/pubmed PY - 2010/8/21/medline SP - 3874 EP - 83 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 51 IS - 8 N2 - PURPOSE: Tumor necrosis factor alpha (TNF)-alpha contributes to inflammation-associated angiogenesis. This study investigates the role of TNF-alpha receptors 1a and 1b in the development of choroidal neovascularization (CNV). METHODS: CNV was induced in Tnfrsf1a(-/-) and Tnfrsf1b(-/-) mice with C57Bl6/J background and their wild-type (WT) (C57Bl/6J) controls by laser damage to the Bruch's membrane. TNF-alpha expression in RPE/choroid was determined by Western blot analysis. Pathologic angiogenesis was estimated qualitatively and quantitatively by fluorescein angiography and histology on choroidal flat mounts and paraffin cross-sections. Inflammatory cell invasion was investigated by clodronic acid depletion of circulating macrophages and immunochemistry, and the apoptotic activity was investigated by TUNEL assay and by caspase-3 and caspase-8 expression. Receptor 1b-specific Bmx/Etk kinase was detected by immunochemistry. RESULTS: TNF-alpha levels were elevated after laser treatment. Severe CNV lesions and increased macrophage invasion were observed in Tnfrsf1a(-/-) compared with WT and Tnfrsf1b(-/-) mice. Increased immunoreactivity for Bmx/Etk kinase corresponded to the severity of CNV formation. Reduced pathologic angiogenesis and macrophage invasion in Tnfrsf1b(-/-) mice (vs. WT and Tnfrsf1a(-/-)) was accompanied by enhanced endothelial cell apoptosis and by caspase-3 and caspase-8 activation. CONCLUSIONS: Receptor 1b promotes the recruitment of inflammatory cells to the site of injury and exacerbated pathologic angiogenesis probably by way of the Bmx/Etk-kinase-dependent pathway in the absence of receptor 1a. On the other hand, receptor 1a-dependent apoptosis in the absence of receptor 1b leads to reduced inflammatory response and CNV lesions after laser treatment. This demonstrates the potential for specific targeting of TNF-alpha receptors for future therapies of inflammation-associated choroidal neovascularization. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/20335614/Differential_role_of_tumor_necrosis_factor__TNF__alpha_receptors_in_the_development_of_choroidal_neovascularization_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.09-5003 DB - PRIME DP - Unbound Medicine ER -