Retina and Posterior Segment

AB017. Investigation of the effect of lymphocyte-derived microparticles on retinal macrophages in the oxygen-induced retinopathy model

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Background: Retinopathy of prematurity (ROP) is the major cause of blindness in children, mainly caused by the retinal neovascularization (NV). Mounting of evidences shown that macrophage plays a pivotal role in the regulation of angiogenesis in ROP. Numerous studies confirmed that the deletion of macrophage significantly reduce the neovascularized areas in the oxygen-induced retinopathy (OIR) model. We have been studied the effect of lymphocyte derived-microparticles (LMPs) over ten years. LMPs are extracellular vesicles derived from apoptotic human CEM T lymphocytes. Our previous studies demonstrated that LMPs possess strong anti-angiogenic effect. Recently we observed that LMPs are capable to switch the phenotype of macrophage, thus to suppress the choroidal neovascularization (CNV). However, the role of LMPs on macrophage in ROP has not been clarified. Thus, my project is to disclose the relationship between LMPs and macrophage in ROP using the OIR model. Hypothesis: LMPs may inhibit retinal NV in the OIR model through targeting at macrophage by affecting the migration of macrophage, thus to inhibit pathological angiogenesis in ROP.

Methods: Cell culture [RAW 264.7 and bone marrow-derived macrophage (BMDM)] for cell migration and viability assay. Generate the OIR model for in vivo detection of macrophage recruitment. Quantification of retinal NV, immunohistostaining of the macrophage in vivo, ex vivo retinal explants for cell migration and qPCR.

Results: LMPs do not affect RAW 264.7 and BMDM cell viability (P>0.05). LMPs significantly decrease the BMDM cell migration indirectly (P<0.05). I successfully generate the OIR model and confirm that more macrophages infiltrate during retinal angiogenesis with counting the F4/80 immunostaining in the retinal flat mount. LMPs exert inhibiting effect on retinal angiogenesis through decreasing the migration of macrophages in vivo.

Conclusions: LMPs have the negative effect on retinal angiogenesis via reducing the infiltrated macrophages to the neovascularized areas in the OIR model.

Editorial
Review Article
Study Protocol

Experimental models of retinopathy of prematurity

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Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.

Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.

Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.

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  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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