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1.
Ophthalmic Res ; 66(1): 681-691, 2023.
Article in English | MEDLINE | ID: mdl-36805961

ABSTRACT

INTRODUCTION: In proliferative diabetic retinopathy (PDR), retinal neovascularization is the essential pathogenic process that is linked to endothelial-to-mesenchymal transition (EndoMT) induced by high glucose (HG). This pathophysiological process may be regulated by a G-protein-coupled chemoattractant receptor FPR2 (mouse Fpr2), involved in inflammatory cell migration and proliferation. In the current study, we investigated the role of Fpr2 in regulating EndoMT and the underlying mechanisms during diabetic retinopathy progression. METHODS: FPR2 agonist or inhibitor was added to human microvascular endothelial cells (HMECs) exposed to normal glucose or HG. Morphologic, phenotypic, and functional changes of HMECs as well as the formation of microvasculature related to EndoMT were assessed. EndoMT biomarkers were detected in the retinal tissues of diabetic mice and fibrovascular epiretinal membranes (FVMs) from patients with PDR. RESULTS: HG upregulated FPR2 in HMECs, which triggered morphological changes, and the cells acquired mesenchymal phenotype, with enhanced cell migration, viability, and angiogenic process shown by tube formation and aortic ring sprouting. Inhibition of FPR2 attenuated HG-induced EndoMT and endothelial cell migration to form vessel-like tube structures. RNA sequence and protein analysis further revealed that inhibition of FPR2 decreased the expression of genes associated with EndoMT. ERK1/2 and P38 signaling pathway was activated in HMECs, promoting neovascularization in HG-induced EndoMT of HMECs. In vivo, increased expression of mesenchymal markers was detected in the retina of diabetic mice and FVMs from patients with PDR. FPR2 deficiency was associated with diminished EndoMT-related phenotypic changes in the retina of diabetic mice. CONCLUSIONS: FPR2 is actively involved in the progression of EndoMT that may contribute to the pathogenesis of PDR. Thus, FPR2 may be a potential therapeutic target for PDR.


Subject(s)
Diabetic Retinopathy , Endothelial-Mesenchymal Transition , Receptors, Formyl Peptide , Animals , Humans , Mice , Diabetes Mellitus, Experimental/complications , Diabetic Retinopathy/pathology , Endothelial Cells/metabolism , Glucose , GTP-Binding Proteins/metabolism , Receptors, Formyl Peptide/genetics , Receptors, Formyl Peptide/metabolism
2.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1187-1194, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36374312

ABSTRACT

PURPOSE: To evaluate the incidence of an opaque bubble layer (OBL) in femtosecond laser-assisted in situ keratomileusis (FS-LASIK) flaps created with VisuMax Flap 2.0 as a result of a modification in the parameters of the flap programming. METHODS: This retrospective study was comprised of 1400 eyes of 715 patients who received FS-LASIK surgery. OBLs were measured and reported as a percentage of the flap area to identify the incidence and extent. Flap creation, which is a modification technique, was performed with 8.1-mm flap diameters plus 0.3-mm enlarged interlamellar photodisruption (group Flap 2.0). The same flap diameters without extra photodisruption as the previous standard setting were also implemented (group Flap 1.0). The preoperative measurements, including sphere, cylinder, keratometry, and intraoperative characteristics such as flap size and thickness, were documented. Possible risk factors for the occurrence of OBLs were investigated in this study. RESULTS: The incidence of an OBL was reduced when using the Flap 2.0 program (31.4%) compared to the Flap 1.0 program (63.7%). The area of hard and soft OBLs created by the Flap 2.0 program is smaller than those created by the Flap 1.0 program (P = 0.007 and P < 0.001). Multivariate logistic regression indicated that a thinner flap (P = 0.038) and a higher sphere (P = 0.001) affected the chance of hard OBLs occurring. CONCLUSION: The VisuMax Flap 2.0 program promotes gas venting by enlarging the interlamellar photodisruption size. The incidence and extent of OBLs appear to be reduced significantly when the Flap 2.0 program is applied.


Subject(s)
Keratomileusis, Laser In Situ , Myopia , Humans , Visual Acuity , Keratomileusis, Laser In Situ/methods , Incidence , Retrospective Studies , Lasers, Excimer/therapeutic use , Corneal Stroma/surgery , Myopia/epidemiology , Myopia/surgery , Corneal Pachymetry
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