Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy

Eye and Vision

Lin Liu¹  Tianqin Wang¹  Mengmeng Jiang¹  Chaoyang Zhang²  Jingfa Zhang²  Haibin Tian³  Hai Xie³  Lixia Lu³  Guo-Tong Xu³ 

[1] Department of Ophthalmology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Pudong New District, 200127, Shanghai, China;Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, 100 Haining Road, Hongkou District, 200080, Shanghai, China;National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China;Tongji Eye Institute, Tongji University School of Medicine, 1239 Siping Road, Medical School Building, Room 623, 200092, Shanghai, China;

关键词: Diabetic retinopathy;    Diabetic macular edema;    Müller cell;    Anti-VEGF;    Intracellular edema;   

DOI  :  10.1186/s40662-021-00237-3

来源: Springer

【 摘 要 】

BackgroundAlthough vascular endothelial growth factor A (VEGF-A) is known to play a key role in causing retinal edema, whether and how VEGF-A induces intracellular edema in the retina still remains unclear.MethodsSprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin. Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset. rMC-1 cells (rat Müller cell line) were treated with glyoxal for 24 h with or without ranibizumab. The expression levels of inwardly rectifying K+ channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), VEGF-A, glutamine synthetase (GS) and sodium-potassium-ATPase (Na+-K+-ATPase) were examined using Western blot. VEGF-A in the supernatant of the cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators.ResultsCompared with normal control, protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro. Similarly, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na+-K+-ATPase protein level remained unchanged, compared with control. However, ranibizumab treatment decreased intracellular sodium, but not potassium.ConclusionRanibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A. It also caused a reduction in intracellular osmotic pressure.

【 授权许可】

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