The role of Interleukin-33 in retinal degenerative diseases
type: CreativeWork
description: Müller cells are the principal glial cells in the retina, and they play an essential role in maintaining retinal homeostasis by supporting neuronal and vascular function. In disease settings, dysregulation of Müller cells leading to their prolonged activation is known to be critical for neurovascular pathology, especially in degenerative conditions such as diabetic retinopathy (DR). Interleukin-33 (IL-33) is expressed in the nuclei of Müller cells in the healthy retina. This cytokine has diverse roles in immunity and inflammation, although its role in Müller cell pathophysiology remains largely unknown. This PhD project has investigated the role of endogenous IL-33 to Müller cell function with emphasis on retinal neuronal degeneration and inflammation, using murine models of experimentally induced retinal detachment (RD) and chemical-induced diabetes. Firstly, immunohistochemistry showed that IL-33 was localised to the nuclei of Müller cells in normal retina. In comparison to wild type (WT) control mice, it was shown that genetic deletion of IL-33 (IL-33KO) did not affect the retinal morphology, function or inflammation. Primary Müller cells (PMC) from WT and IL-33KO mice were isolated and characterised. A novel, spontaneously immortalised murine Müller glial cell line QMMuC-1 was also generated. Following RD, in WT mice, the expression of the inflammatory cytokines IL-1β, IL-6, CCL2, TNF∝, TGFβ and IL-33 were significantly increased at day 1 and then reduced gradually and returned to basal level by day 28. In IL-33KO mice, RD induced an exacerbated inflammation with increased CCL2, TNF∝, TGFβ and GFAP expression and sustained immune cells infiltration was exhibited for at least 28 days. Electroretinography (ERG) revealed lower a- and b-wave amplitudes at day 28 post-RD in IL-33KO mice compared to WT RD mice. The numbers of cone photoreceptor cells and their synapses were significantly lower in the retina of IL-33KO mice subjected to experimental RD compared to WT c…
abstract: Müller cells are the principal glial cells in the retina, and they play an essential role in maintaining retinal homeostasis by supporting neuronal and vascular function. In disease settings, dysregulation of Müller cells leading to their prolonged activation is known to be critical for neurovascular pathology, especially in degenerative conditions such as diabetic retinopathy (DR). Interleukin-33 (IL-33) is expressed in the nuclei of Müller cells in the healthy retina. This cytokine has diverse roles in immunity and inflammation, although its role in Müller cell pathophysiology remains largely unknown. This PhD project has investigated the role of endogenous IL-33 to Müller cell function with emphasis on retinal neuronal degeneration and inflammation, using murine models of experimentally induced retinal detachment (RD) and chemical-induced diabetes. Firstly, immunohistochemistry showed that IL-33 was localised to the nuclei of Müller cells in normal retina. In comparison to wild type (WT) control mice, it was shown that genetic deletion of IL-33 (IL-33KO) did not affect the retinal morphology, function or inflammation. Primary Müller cells (PMC) from WT and IL-33KO mice were isolated and characterised. A novel, spontaneously immortalised murine Müller glial cell line QMMuC-1 was also generated. Following RD, in WT mice, the expression of the inflammatory cytokines IL-1β, IL-6, CCL2, TNF∝, TGFβ and IL-33 were significantly increased at day 1 and then reduced gradually and returned to basal level by day 28. In IL-33KO mice, RD induced an exacerbated inflammation with increased CCL2, TNF∝, TGFβ and GFAP expression and sustained immune cells infiltration was exhibited for at least 28 days. Electroretinography (ERG) revealed lower a- and b-wave amplitudes at day 28 post-RD in IL-33KO mice compared to WT RD mice. The numbers of cone photoreceptor cells and their synapses were significantly lower in the retina of IL-33KO mice subjected to experimental RD compared to WT c…
author: Augustine, Josy
language: eng
keywords: Interleukin-33, IL-33, Diabetic Retinopathy, Diabetes, Cytokines, neurodegeneration, Müller cells, Muller, cellline, QMMuC-1, josy augustine, gliosis, glial activation, microglia, macrophages, photoreceptors
date published: 2020-7
date modified: 2026-07-24T03:55:12Z
provider: Queen's University Belfast
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queen's University Belfast