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Age-related macular degeneration(ARMD)is the leading cause of blindness in the elderly. Studies have shown that the regulation disorder of extracellular matrix(ECM)is one of the important characteristics of ARMD, and its damage can be sustained throughout the disease course. Additionally, various cell types participate in the formation and abnormal deposition of ECM under the control of multiple signals. Subsequently, they transmit signals that regulate adhesion, migration, proliferation, apoptosis, survival or differentiation, which lead to the destruction of the retinal and choroidal microenvironment, immune dysfunction, infiltrative inflammatory cell differentiation, neovascularization and epithelial mesenchymal transformation, and ultimately lead to subretinal fibrosis, scarring and severe visual impairment in advanced ARMD. Therefore, increasing attention has been paid to the role of ECM in ARMD in recent years. This article reviews the relationship between retinal ECM and ARMD and the role between ECM and various types of cells in ARMD, hoping to provide guidance for the research direction of ARMD treatment.
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@#AIM:To establish the hypoxia induced endothelial-mesenchymal transition(EndoMT)model of endothelial cells, and to investigate the effect and mechanism of Pirfenidone(PFD)on inhibiting the subretinal fibrosis progression.<p>METHODS: Primary cultured human umbilical vein endothelial cells(HUVEC), 4-7 passages were used for experiments after cell identification. CoCl<sub>2</sub> induced hypoxia to establish the transformation model of endothelial cells into fibroblasts. CCK-8 was performed to detect cell proliferation rate and chose the optimal drug concentration. All cells were divided into 4 groups: control group(FBS-free), CoCl<sub>2</sub>(200μmol/L)group, CoCl<sub>2</sub>+0.3mg/mL PFD group, CoCl<sub>2</sub>+0.6mg/mL PFD group. The protein expression of CD31, VE-cadherin, α-SMA, FSP1, p-p38 and p38 were detected by Western blot. Double immunofluorescence labeling method was used to observe the CD31/α-SMA expression. Wound healing assay detected the cell migration. The q-PCR was applied to detect the mRNA levels of TGF-β1 and SNAI1.<p>RESULTS: Compared with CoCl<sub>2</sub> group, PFD increased cell proliferation rate and inhibited cell migration significantly under hypoxia(<i>P</i><0.05). PFD decreased the protein expression of the mesenchymal markers α-SMA and FSP1, and increased the protein level of the endothelial markers CD31 and VE-cadherin(<i>P</i><0.05). Double immunofluorescence results showed that PFD could reduce the expression of α-SMA and increase the level of CD31(<i>P</i><0.05). In the process of EndoMT, the p38 protein expression level was stable(<i>P</i>>0.05). PFD down-regulated significantly the high protein expression of p-p38, and high mRNA expression of TGF-β1 and SNAI1 compared with control group(<i>P</i><0.05). There was no significant difference between the 0.3 and 0.6mg/mL PFD groups in all results above.<p>CONCLUSION: PFD can inhibit the formation of fibrosis in endothelial cells. TGF-β/p38MAPK signaling pathway might be one of the mechanisms that PFD regulates EndoMT progression. PFD will be expected to become a potential new sight on the treatment of subretinal fibrosis.
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Objective • To establish the transforming growth factor-β2 (TGF-β2) induced epithelial-mesenchymal transition (EMT) model of retinal pigment epithelium cells, and investigate the effect and mechanism of lutein on EMT. Methods • ARPE-19 cells were cultured and divided into 4 groups including control group, TGF-β2 group, TGF-β2+lutein group and lutein group. The mRNA levels of α-smooth muscle actin (α-SMA), fibronectin (FN) and E-cadherin were analyzed by real-time PCR. The protein expression of α-SMA, FN and occludin were assayed by Western blotting. Immunofluorescence was used to detect the change of α-SMA. Meanwhile, Western blotting was performed to detect the expression levels of pSmad3 in the TGF/Smad signaling pathway. Results • TGF-β2 induced EMT was inhibited by lutein. Lutein decreased the mRNA and protein levels of the mesenchymal markers α-SMA and FN, and increased the expression of the epithelial markers E-cadherin and occludin (all P<0.05). Immunofluorescence showed that lutein can inhibit the conversion of epithelial cells into myofibroblasts. Lutein significantly downregulated the high expression of pSmad3 in TGF-β2 treated ARPE-19 cells (P=0.001). Conclusion • Lutein inhibits TGF-β2 induced EMT by downregulating the expression of pSmad3 in TGF-β/Smad signaling pathway, indicating it may attenuate subretinal fibrosis.
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We report a rare finding of progressive subretinal fibrosis mimicking retinal necrosis in 2 cases of sympathetic ophthalmia. Histopathology of the inciting eye and vitreous biopsy of the sympathizing eye ruled out infections and masquerades. Progression of inflammation and rapid deterioration of vision inspite of maximum immunosuppression are key findings in this variant of sympathetic ophthalmia.
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Subretinal fibrosis contributes to the loss of vision associated with agerelated macular degeneration.Anti-vascular endothelial growth factor therapy is the current standard treatment for exudative age-related macular degeneration.In this review,many risk factors of subretinal fibrosis are discussed,the relationship between anti-vascular endothelial growth factor therapy and subretinal fibrosis,some potential novel therapeutic methods to suppresses subretinal fibrosis are also revealed.