Potential regulatory molecules in the human trabecular meshwork of patients with glaucoma: Immunohistochemical profile of a number of inflammatory cytokines

Samanta Taurone, Guido Ripandelli, Elena Pacella, Enrica Bianchi, Andrea Maria Plateroti, Stefania De Vito, Pasquale Plateroti, Francesca Romana Grippaudo, Carlo Cavallotti, Marco Artico

Research output: Contribution to journalArticlepeer-review

Abstract

Glaucoma occurs when there are imbalances between the production and the drainage of the eye liquid. The vast majority of the aqueous humor leaves the eye through the trabecular meshwork (TM). The cause of hypertonicity may be due to an alteration in the thickness of the TM. In the majority of cases the molecular changes that determine primary openangle glaucoma (POAG) are unclear. However, it has been hypothesized that the significant increase in the extracellular matrix (ECM) of the fibrillary bands in the TM is associated with possible inflammatory conditions. In this study the tissue distribution of interleukin (IL)6, IL1β, transforming growth factor-β1 (TGFβ1), vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNFα) was analyzed in TM samples from patients with POAG by immunohistochemistry. Seven specimens from patients with POAG and three control tissues were analyzed by immunohistochemistry using specific antibodies against these cytokines. Morphological changes in the TM, such as increased cell content, macrophages, fibrosis and accumulation of neutrophils, were observed by transmission electron microscopy. In human TM tissues, an evident immunoreactivity for IL6, IL1β and TNFα was observed in patients with POAG when compared with the control subjects, indicating that these cytokines may be correlated with disease activity. TM endothelial cells secrete a number of factors and cytokines that modulate the functions of the cells and the ECM of the conventional outflow pathway. In the TM in glaucoma, macrophages produce cytokines, including IL6, IL1β and TNFα, leading to an acute inflammatory response and recruitment of other immune cells, including T lymphocytes. In addition, TGFβ1 regulates and induces the expression of IL6 in TM that indirectly induces angiogenesis by stimulating VEGF expression. The present results support previous evidence that suggests that growth factors and cytokines can induce ECM remodelling and alter cytoskeletal interactions in the TM.

Original languageEnglish
Pages (from-to)1384-1390
Number of pages7
JournalMolecular Medicine Reports
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Keywords

  • Immunohistochemistry
  • Interleukin1β
  • Interleukin6
  • Intraocular pressure
  • Primary openangle glaucoma
  • Tumor growth factor β1
  • Tumor necrosis factor α
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Oncology
  • Medicine(all)

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