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Galectin‐1 studies in proliferative diabetic retinopathy
Author(s) -
Abu ElAsrar Ahmed M.,
Ahmad Ajmal,
Allegaert Eef,
Siddiquei Mohammad Mairaj,
Alam Kaiser,
Gikandi Priscilla W.,
De Hertogh Gert,
Opdenakker Ghislain
Publication year - 2020
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.14191
Subject(s) - cd31 , angiogenesis , diabetic retinopathy , western blot , neovascularization , immunohistochemistry , galectin 1 , endothelial stem cell , vascular endothelial growth factor , microvessel , retinal , pathology , biology , microbiology and biotechnology , medicine , endocrinology , immunology , cancer research , diabetes mellitus , in vitro , biochemistry , gene , vegf receptors
Abstract Purpose Galectin‐1 regulates endothelial cell function and promotes angiogenesis. We investigated the hypothesis that galectin‐1 may be involved in the pathogenesis of proliferative diabetic retinopathy ( PDR ). Methods Vitreous samples from 36 PDR and 20 nondiabetic patients, epiretinal fibrovascular membranes from 13 patients with PDR , rat retinas and human retinal Müller glial cells were studied by enzyme‐linked immunosorbent assay ( ELISA ), immunohistochemistry and Western blot analysis. In vitro angiogenesis assays were performed and the adherence of leukocytes to galectin‐1‐stimulated human retinal microvascular endothelial cells ( HRMEC s) was assessed. Results The ELISA analysis revealed that galectin‐1 and vascular endothelial growth factor ( VEGF ) levels were significantly higher in vitreous samples from PDR patients than in those from nondiabetics (p < 0.001 for both comparisons). A significant positive correlation was found between the levels of galectin‐1 and VEGF ( r = 0.354; p = 0.022). In epiretinal membranes, immunohistochemical analysis showed that galectin‐1 was expressed in vascular endothelial cells expressing CD 31, myofibroblasts expressing α ‐smooth muscle actin and leukocytes expressing CD 45. The galectin‐1 receptor neuropilin‐1 was expressed on vascular endothelial cells. CD 31 staining was used as a marker to assess microvessel density ( MVD ). Significant positive correlation was detected between MVD in epiretinal membranes and the number of blood vessels expressing galectin‐1 ( r = 0.848; p < 0.001). Western blot analysis demonstrated significant increase of galectin‐1 protein in rat retinas after induction of diabetes. ELISA analysis revealed that hydrogen peroxide and cobalt chloride (CoCl 2 ) induced upregulation of galectin‐1 in Müller cells. Treatment with galectin‐1 induced upregulation of VEGF in Müller cells and increased leukocyte adhesion to HRMEC s. The galectin‐1 inhibitor OTX 008 attenuated VEGF ‐induced HRMEC s migration and CoCl 2 ‐induced upregulation of NF ‐ κ B, galectin‐1 and VEGF in Müller cells. Conclusions These results suggest that galectin‐1is involved in the pathogenesis of PDR .