Year: 2020
Type: article
Abstract: The aim of the current study was to investigate the impact of long-acting fibroblast growth factor 21 (FGF21) on retinal vascular leakage utilizing machine learning and to clarify the mechanism underlying the protection. To assess the effect on retinal vascular leakage, C57BL/6J mice were pre-treated with long-acting FGF21 analog or vehicle (Phosphate Buffered Saline; PBS) intraperitoneally (i.p.) before induction of retinal vascular leakage with intravitreal injection of mouse (m) vascular endothelial growth factor 164 (VEGF164) or PBS control. Five hours after mVEGF164 injection, we retro-orbitally injected Fluorescein isothiocyanate (FITC) -dextran and quantified fluorescence intensity as a readout of vascular leakage, using the Image Analysis Module with a machine learning algorithm. In FGF21- or vehicle-treated primary human retinal microvascular endothelial cells (HRMECs), cell permeability was induced with human (h) VEGF165 and evaluated using FITC-dextran and trans-endothelial electrical resistance (TEER). Western blots for tight junction markers were performed. Retinal vascular leakage in vivo was reduced in the FGF21 versus vehicle- treated mice. In HRMECs in vitro, FGF21 versus vehicle prevented hVEGF-induced increase in cell permeability, identified with FITC-dextran. FGF21 significantly preserved TEER compared to hVEGF. Taken together, FGF21 regulates permeability through tight junctions; in particular, FGF21 increases Claudin-1 protein levels in hVEGF-induced HRMECs. Long-acting FGF21 may help reduce retinal vascular leakage in retinal disorders and machine learning assessment can help to standardize vascular leakage quantification.
DOI: 10.3390/ijms21041188
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Funders: Foundation for the National Institutes of Health, Boston Children's Hospital, Little Giraffe Foundation, Deutsche Forschungsgemeinschaft, Manpei Suzuki Diabetes Foundation, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, Manton Center for Orphan Disease Research, Boston Children's Hospital, National Eye Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1024040356, G3243568557, The Mechanism of Immune-Vascular Crosstalk in Retinopathy, Photoreceptor Determination of Retinal Blood Vessel Growth in Retinopathy, G3916677169, G5541998881, G5586389099, Boston Intellectual and Developmental Disabilities Research Center, G6471330961, G6620266270, Glucose/lipid metabolism and vessel development in phase I ROP, G773623065, G8498514485, Dietary control of angiogenesis in retinopathy models
OpenAlex ID: W3006265516