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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Animals, Newborn, Blotting, Western, Cells, Cultured, Disease Models, Animal, Ephrin-A4, Follow-Up Studies, Gene Expression Regulation, Developmental, Immunohistochemistry, Mice, Mice, Inbred C57BL, RNA, Real-Time Polymerase Chain Reaction, Retinal Neovascularization, Retinal Pigment Epithelium, Signal Transduction, Vascular Endothelial Growth Factor A.
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Is ephrin-a4 involved in retinal neovascularization by regulating the VEGF signaling pathway? Context: Retinal neovascularization (NV) is a major cause of blindness. Recent research suggests that factors other than VEGF participate in this process. This study aimed to determine the role of ephrin-A4 in retinal NV. The expression and effect of ephrin-A4 was investigated in a mouse model of oxygen-induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4 expression and VEGF signaling pathway phosphorylation were determined by PCR, immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin-A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro. Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and RPE cells after CoCl₂ stimulation. In vitro, Ephrin-A4/Fc treatment significantly increased the tube number of RF/6A cells on a membrane preparation and the phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover, ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and inhibited the proliferation and tube formation capacity of RF/6A cells in vitro. Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1, and ERK1/2 was defective under VEGF₁₆₅ stimulation, and the proangiogenic function of VEGF₁₆₅ was also compromised.
assistant
This study suggests that ephrin-A4 plays an important role in retinal NV and is a potential target against retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial role in the VEGF signaling pathway. Final Decision: yes