Expression of Angiogenic and Inflammatory Factors in Choroidal Neovascularisation-Derived Retinal Pigment Epithelium

Abstract

Purpose: Anti-angiogenic treatment is well established in the management of exudative age-related macular degeneration (AMD), but not sufficient in all patients. The characterisation of factors driving this chronic disease could serve to identify additional treatment options. The purpose of this study was to assess gene expression patterns and distinct changes in cells derived from surgically extracted choroidal neovascularisation (CNV) membranes. Materials and Methods: The expression of >11,000 genes was analysed by means of a microarray in cells cultured from 2 late-stage CNV membranes compared to primary human retinal pigment epithelium (RPE) and ARPE-19 cells. A pathway analysis was performed to identify gene expression patterns associated with exudative AMD. Results: The analysis revealed significant alterations in gene sets associated with inflammatory processes in CNV-derived cells, involving the upregulation of pro-inflammatory factors IL6, C3, and C5, and downregulation of anti-inflammatory complement factor B and complement factor I. Factors associated with angiogenesis, such as VEGFA or ANGPT2, were not significantly regulated in the 2 RPE-derived cell lines. Conclusion: In late-stage CNV membrane-derived RPE, gene expression was shifted towards a pro-inflammatory state. Angiogenesis-associated factors were regulated differently in the 2 CNV-derived RPE membranes. While inflammation seems to be continuously stimulated by RPE associated with late exudative AMD, this appears not to be the case with regard to angioregulatory mechanisms.

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

“…As a first-line therapy, intravitreal injection of antivascular endothelial growth factor (VEGF) agents is effective in patients with nAMD because it targets pathological CNV (Kovach et al, 2012;Ferrara and Adamis, 2016). However, the limitations of anti-VEGF therapy should not be ignored, such as the side effects of the injection (Xi, 2020) and the unsatisfactory duration of the therapeutic effect (Ehlken et al, 2019). In addition, long-term use of anti-VEGF therapy may lead to serious economic burdens, especially in developing countries and regions (Ruiz-Moreno et al, 2021).…”

Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells

“…Here, we integrated text mining data, 3 angiogenesis‐related protein‐protein interaction networks 30,31 and multi‐experiment microarray data 32‐34 to find out candidate genes involved in VEGFA/VEGFR2 signalling pathways. We then aimed to do topological analysis of candidate genes’ biological networks to determine selected genes and to search for in vitro effects of Aflibercept on expression of selected genes in endothelial cells.…”

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

“…[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.…”