Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma.

Keitaro Hase,Satoru Kase,Atsuhiro Kanda,Kousuke Noda,Yasuhiro Shinmei,Susumu Ishida

doi:10.3390/jcm10132977

Keitaro Hase, Satoru Kase + Show 4 more

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https://doi.org/10.3390/jcm10132977

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Journal: Journal of Clinical Medicine	Publication Date: Jul 2, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Hokkaido University

Abstract

: PurposeTo investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma.

Highlights

Glaucoma is a progressive degenerative optic neuropathy and is a leading cause of irreversible blindness in the world [1]
vascular endothelial growth factor (VEGF)-C immunoreactivity was found in the trabecular meshwork (TM), Schlemm’s canal endothelial cells and collecting ducts from the patient with Neovascular glaucoma (NVG) secondary to Proliferative diabetic retinopathy (PDR) (Figure 1A–C) and with
VEGF-C immunoreactivity was not observed in the TM or Schlemm’s canal endothelial cells (Figure 1G–I)

Summary

Introduction

Glaucoma is a progressive degenerative optic neuropathy and is a leading cause of irreversible blindness in the world [1]. Neovascular glaucoma (NVG) is a form of secondary angle-closure glaucoma characterized by neovascularization of the angle, which causes occlusion of the TM [4]. Proliferative diabetic retinopathy (PDR) and retinal vein occlusion with angiogenesis are important as causative diseases of NVG [5]. It has been reported that the mean concentration of VEGF-A in aqueous humor of patients with NVG was significantly higher than that in patients with primary open-angle glaucoma (POAG) and cataract [7]. Though new treatments for glaucoma such as eyedrops, laser therapy, and surgery have been developed to slow visual field loss by lowering intraocular pressure, many patients still lose their eyesight due to glaucoma [11,12]

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