Inflammasome upregulation and activation in photoreceptors of type 2 diabetes and N-methyl-N-nitrosourea models is attenuated by Wedelolactone
type: CreativeWork
description: Inflammation is known to play an important role in the pathogenesis of diabetic retinopathy (DR) and some aspects of retinal neurodegeneration although the precise underlying mechanisms linking these pathologies are not fully understood. Inflammation and oxidative damage are linked pathogenic processes that are enhanced during obesity and type 2 diabetes mellitus (T2DM). Building on this, there is some recent evidence suggesting an important role of the inflammasome which may link these pathways, especially in T2DM. With focus on the diabetic retina, activation of the inflammasome in the retina and how it may differ between type 1 diabetes mellitus (T1DM) and T2DM has not yet been determined. There are several types of inflammasome but the so-called AIM2 inflammasome pathway may be the most important in this disease context, since it critically controls the production and maturation of pro-inflammatory cytokines, including IL1B and IL18 via canonical (CASP1) and non-canonical pathways (CASP4/11). Oxidative stress plays an important role in vascular and neurodegenerative changes in DR and has been shown to induce mitochondrial dysfunction in various retinal cells where it can manifest as loss of organelle membrane integrity and porosity, leading to the extravasation of mtDNA. In such scenarios, AIM2 inflammasome signalling is activated in response to DNA-sensing, leading to inflammation and cell death. Wedelolactone has been previously identified as a novel CASP4/11 inhibitor and its potential to modulate the inflammasome cascade may provide protection against diabetes-linked retinal neurodegeneration. Murine models of T1DM (Ins2Akita and Streptozotocin-induced diabetes) and T2DM (BKsCgm+/+lepr) were used to determine the retinal inflammasome expression profile. This was conducted in conjunction with human ocular samples donated from age-matched controls with no-diabetes, T1DM, T2DM and T2D with DR (T2DM-DR). The role of free fatty acid palmitate was also assessed fo…
abstract: Inflammation is known to play an important role in the pathogenesis of diabetic retinopathy (DR) and some aspects of retinal neurodegeneration although the precise underlying mechanisms linking these pathologies are not fully understood. Inflammation and oxidative damage are linked pathogenic processes that are enhanced during obesity and type 2 diabetes mellitus (T2DM). Building on this, there is some recent evidence suggesting an important role of the inflammasome which may link these pathways, especially in T2DM. With focus on the diabetic retina, activation of the inflammasome in the retina and how it may differ between type 1 diabetes mellitus (T1DM) and T2DM has not yet been determined. There are several types of inflammasome but the so-called AIM2 inflammasome pathway may be the most important in this disease context, since it critically controls the production and maturation of pro-inflammatory cytokines, including IL1B and IL18 via canonical (CASP1) and non-canonical pathways (CASP4/11). Oxidative stress plays an important role in vascular and neurodegenerative changes in DR and has been shown to induce mitochondrial dysfunction in various retinal cells where it can manifest as loss of organelle membrane integrity and porosity, leading to the extravasation of mtDNA. In such scenarios, AIM2 inflammasome signalling is activated in response to DNA-sensing, leading to inflammation and cell death. Wedelolactone has been previously identified as a novel CASP4/11 inhibitor and its potential to modulate the inflammasome cascade may provide protection against diabetes-linked retinal neurodegeneration. Murine models of T1DM (Ins2Akita and Streptozotocin-induced diabetes) and T2DM (BKsCgm+/+lepr) were used to determine the retinal inflammasome expression profile. This was conducted in conjunction with human ocular samples donated from age-matched controls with no-diabetes, T1DM, T2DM and T2D with DR (T2DM-DR). The role of free fatty acid palmitate was also assessed fo…
author: Harkin, Kevin
language: eng
keywords: Inflammasome, wedelolactone, diabetic retinopathy, retinal degeneration
date published: 2021-7
date modified: 2026-07-24T03:55:45Z
provider: Queen's University Belfast
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queen's University Belfast