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

ABSTRACT

Purpose

To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163⁺ M2 macrophages in proliferative diabetic retinopathy (PDR).

Methods

Vitreous samples from 29 PDR and 19 nondiabetic patients, epiretinal fibrovascular membranes from 15 patients with PDR and Müller cells were studied by enzyme-linked immunosorbent assay, immunohistochemistry and Western blot analysis.

Results

We showed a significant increase in expression of IL-11, soluble(s) IL-11Rα, sCD163 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls. Significant positive correlations were found between levels of VEGF and levels of IL-11 and sCD163. Significant positive correlations were found between microvessel density and number of blood vessels and stromal cells expressing IL-11, IL-11Rα and CD163 in PDR epiretinal membranes. The hypoxia mimetic agent cobalt chloride induced upregulation of IL-11 and IL-11Ra in cultured Müller cells.

Conclusions

IL-11/IL-11Rα signaling and CD163⁺ M2 macrophages might be involved in PDR angiogenesis.

Keywords:

• Angiogenesis
• CD163
• IL-11
• IL-11Rα
• inflammation
• M2 macrophages
• proliferative diabetic retinopathy

Acknowledgments

The authors thank Ms. Kathleen van den Eynde and Mr. Wilfried Versin for technical assistance and Ms. Connie Unisa-Marfil for secretarial work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was supported by the Foundation for Scientific Research of Flanders (FWO-Vlaanderen) and C1 funding (2017-2023) of the KU Leuven (Opdenakker G);King Saud University through Vice Deanship of Research Chair (Dr. Nasser Al-Rashid Research Chair in Ophthalmology, Abu El-Asrar AM).