Correlation between ELF-PEMF exposure and Human RPE Cell Proliferation, Apoptosis and Gene Expression.

Morteza Oladnabi,Rouhallah Najjar Sadeghi,Mozhgan Rezaeikanavi,Abouzar Bagheri,Mehryar Zargari,Mohammad Amir Mishan

doi:10.18502/jovr.v16i2.9084

Abstract

Purpose Emerging evidence implies that electromagnetic fields (EMFs) can negatively affect angiogenesis. In this regard, the effects of extremely low frequency pulsed electromagnetic field (ELF–PEMF) exposure on the relative expression level of angiogenic factors involved in the pathogenesis of ocular disorders were evaluated in human retinal pigment epithelial (hRPE) cells in order to investigate a noninvasive therapeutic method for patients with several ocular diseases associated with neovascularization.MethodsAfter separating hRPE cells from globes, hRPE cells were exposed to 15 mT of ELF–PEMF (120 Hz) at 5, 10, and 15 min for seven days. Cell proliferation and apoptosis of treated cells were evaluated via ELISA assay. Moreover, relative expression changes of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 were performed using real-time RT-PCR.Results ELF–PEMF exposure had no significant effects on the apoptosis and proliferation rate of hRPE cells. Expression level of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 was downregulated following 5 min of ELF–PEMF exposure.ConclusionAs ELF–PEMF showed inhibitory effects on the expression of angiogenic genes in hRPE cells with no cytotoxic or proliferative side effects, it can be introduced as a useful procedure for managing angiogenesis induced by retinal pathogenesis, although more studies with adequate follow-up in animal models are needed.

Highlights

Hypoxia is an important regulator of cell migration and angiogenesis, especially under pathologic conditions, which perform its action by upregulating hypoxiainducible factor 1 (HIF-1) and vascular endothelial growth factor A (VEGFA).[8,9,10,11]
Effects of ELF–PEMF on the cell proliferation and apoptosis of human retinal pigment epithelial (hRPE) cells were examined by ELISA
The findings showed that ELF–PEMF did not influence cell proliferation (Figure 2)

Summary

Introduction

Neovascularization, a process of forming new vessels occurs during physiological development and pathological events, involved in several ocular diseases such as age-related macular degeneration (AMD), ischemic retinal vein occlusion, glaucoma, corneal neovascularization secondary to chemical injury or infection, diabetic retinopathy (DR), and inflammatory processes.[1,2,3] Through the production of different fibrotic and angiogenic factors in choroidal neovascular membranes, retinal pigment epithelial (RPE) cells contribute to choroidal neovascularization (CNV) and paracrine signaling between choriocapillaris and RPE layer.[4,5,6,7] Hypoxia is an important regulator of cell migration and angiogenesis, especially under pathologic conditions, which perform its action by upregulating hypoxiainducible factor 1 (HIF-1) and vascular endothelial growth factor A (VEGFA).[8,9,10,11] VEGFA mainly regulates angiogenesis, contributing to the migration and proliferation of vascular endothelial cells and tube formation, which increase vascular permeability in angiogenesis.[12] The VEGF/VEGFR signaling pathway is involved in the activation of multiple angiogenic factors, including matrix metalloproteinases (MMPs), cathepsins, connective tissue growth factor (CTGF), and E2Fs.[13, 14] CTGF can help regulation of the extracellular matrix (ECM) turnover and a relationship is found between CTGF and CNV.[15] In addition, matrix-degrading proteinases including MMPs and cathepsins induce angiogenesis through facilitating endothelial cell penetration in the subendothelial matrix.[16, 17]

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