TIMP-3 suppression induces choroidal neovascularization by moderating the polarization of macrophages in age-related macular degeneration. (February 2019)

• Record Type: Journal Article
• Authors: Cheng, Ying; Cheng, Tongjie; Qu, Yi
• Is Part Of: Molecular immunology. Volume 106(2019:Feb.)
• Page Start: 119
• Page End: 126
• Publication Date: 2019-02
• Subjects: Choroidal neovascularization -- Macrophages -- Polarization -- Tissue inhibitor of metalloproteinases–3; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.12.026
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TIMP-3 suppression could alter the macrophage polarization to M2 type in bone marrow-derived macrophages. siR-TIMP-3 regulates macrophage polarization to a more pro-angiogenic subtype in RPE/Choroidal tissues with CNV animal model. OCTA is effective to observe the CNV lesion in BN rat eye, indicating the absence of TIMP-3 might accelerate the growth of CNV lesions. Abstract: Purpose: To investigate the role of tissue inhibitor of metalloproteinases–3 (TIMP-3) as a key moderator of macrophage polarization in choroidal neovascularization (CNV) lesions of model mice and in bone marrow-derived macrophage (BMDM). Method: We used siR-TIMP-3 to transfect BMDM and gave an intravitreal injection of siR-TIMP-3 to laser-induced CNV mice model, real time-PCR and western blot were applied for detecting the expressions of TIMP-3 and macrophages' biomarker. Besides, CNV lesions in different treatment groups of animal model were examined by the optical coherence tomography angiography (OCTA). Results: Our experimental data showed that lack of TIMP-3 stimulated M2 polarization proved by real time-PCR and western blot in BMDMs and CNV mice model. Moreover, intravitreal injection of siR-TIMP-3 accelerated CNV formation using OCTA, which indicated that TIMP-3 suppression is related to pro-angiogenesis of M2 macrophage. Conclusion: We showed that the absence of TIMP-3 leads to a more pro-angiogenic microenvironment, playing a key role in CNV formation by positively modulating M2 polarization. The role of TIMP-3 in the regulating inflammation and novel therapeutic target of nAMD needs to be further studied.