Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative

Ahmed M Abu El-Asrar1,2, Ajmal Ahmad1, Eef Allegaert3

  • 1Department of Ophthalmology, College of Medicine, King Saud University , Riyadh, Saudi Arabia.

Abstract

Insights

Interleukin-11 (IL-11) and Interleukin-11 receptor alpha (IL-11Rα) signaling, along with CD163-positive M2 macrophages, are implicated in proliferative diabetic retinopathy (PDR) angiogenesis. These factors show increased expression in PDR patients, correlating with disease severity.

Area of Science:

  • Ophthalmology
  • Immunology
  • Molecular Biology

Background:

  • Proliferative diabetic retinopathy (PDR) is a leading cause of vision loss.
  • Diabetic retinopathy is characterized by abnormal blood vessel growth (angiogenesis).
  • The role of specific molecular signaling pathways in PDR pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the expression of Interleukin-11 (IL-11) and its receptor IL-11 receptor alpha (IL-11Rα) in PDR.
  • To quantify the density of CD163-positive M2 macrophages in PDR.
  • To explore the relationship between IL-11/IL-11Rα and M2 macrophages in PDR.

Main Methods:

  • Vitreous samples from PDR patients and nondiabetic controls were analyzed using enzyme-linked immunosorbent assay (ELISA).
  • Epiretinal membranes from PDR patients and cultured Müller cells were examined via immunohistochemistry and Western blot.
  • Expression levels of IL-11, IL-11Rα, soluble CD163 (sCD163), and vascular endothelial growth factor (VEGF) were quantified.

Main Results:

  • Significantly elevated levels of IL-11, soluble IL-11Rα (sIL-11Rα), sCD163, and VEGF were observed in the vitreous of PDR patients compared to controls.
  • Positive correlations were found between VEGF levels and IL-11/sCD163 levels, as well as between microvessel density and cells expressing IL-11, IL-11Rα, and CD163 in epiretinal membranes.
  • Hypoxia induced upregulation of IL-11 and IL-11Rα in cultured Müller cells.

Conclusions:

  • The IL-11/IL-11Rα signaling pathway is likely involved in the angiogenesis characteristic of PDR.
  • CD163-positive M2 macrophages may play a role in the pathogenesis of PDR.
  • These findings suggest potential therapeutic targets for managing PDR.

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