Pro-inflammatory and anti-angiogenic effects of bisphosphonates on human cultured retinal pigment epithelial cells
- 13 June 2013
- journal article
- laboratory science
- Published by BMJ in British Journal of Ophthalmology
- Vol. 97 (8), 1074-1078
- https://doi.org/10.1136/bjophthalmol-2013-303355
Abstract
Aim Bisphosphonates have been shown to induce ocular inflammatory diseases such as uveitis and scleritis, while being protective against angiogenic diseases like neovascular age-related macular degeneration (AMD). Therefore, we studied the effects of bisphosphonates on primary culture of human fetal retinal pigment epithelium (hRPE), a cell type known to secrete both inflammatory and angiogenic factors. Alendronate and etidronate were selected for this experiment as they are members of the two structurally different classes of bisphosphonates. Methods Primary cultures of hRPE were serum-starved for 24 h and then treated for 24 h with alendronate (0.0001, 0.1, 100 µM) or etidronate (0.01, 1 µM). Cell viability was measured using the MTT assay. Investigation of secreted cytokines induced by bisphosphonates was performed using a human cytokine 29-Plex Panel (Bio-Plex) array and the results were analysed with an analysis of variance (ANOVA). Results Etidronate, at the lower concentration, significantly increased the expression of interleukin (IL)-6 (p=0.03) and IL-8 (p=0.04). At the higher concentration, etidronate significantly decreased the expression of granulocyte macrophage colony-stimulating factor (p=0.02) and basic fibroblast growth factor (bFGF) (p=0.02). Alendronate, at the highest concentration, significantly increased the expression of IL-8 (p=0.02) and decreased the expression of eotaxin (p=0.02). Alendronate also significantly decreased the expression of bFGF at all concentrations (pConclusions Alendronate and etidronate display dose dependent effects in hRPE cells. Alendronate and etidronate administration resulted in concentration dependent elevations in inflammatory cytokines. Furthermore, alendronate and etidronate administration resulted in reduced expression of a number of angiogenic factors. These findings may explain the increased incidence of ocular inflammation as well as the therapeutic effect on neovascular AMD which have been described with bisphosphonates.Keywords
This publication has 46 references indexed in Scilit:
- Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort studyCMAJ : Canadian Medical Association Journal, 2012
- Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapyBritish Journal of Ophthalmology, 2011
- The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatmentEye, 2010
- Therapeutic Effect of Oral Bisphosphonates on Choroidal Neovascularization in the Human EyeJournal of Ophthalmology, 2010
- CCR3 is a target for age-related macular degeneration diagnosis and therapyNature, 2009
- Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitisRheumatology, 2009
- TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1Nature Medicine, 2007
- Ranibizumab for Neovascular Age-Related Macular DegenerationThe New England Journal of Medicine, 2006
- Synthesis and Secretion of Vascular Permeability Factor/Vascular Endothelial Growth Factor by Human Retinal Pigment Epithelial CellsBiochemical and Biophysical Research Communications, 1993
- Basic fibroblast growth factor is synthesized in cultured retinal pigment epithelial cellsBiochemical and Biophysical Research Communications, 1987