Unravelling the therapeutic potential of IL-33 for atrophic AMD

Clare, Alison J; Jian, Liu; Copland, David A; Theodoropoulou, Sofia; Dick, Andrew D

doi:10.1038/s41433-021-01725-5

Cited by 7 publications

(10 citation statements)

References 94 publications

(128 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…79,80 When the long-term struggle between pro-and anti-inflammatory responses ultimately loses balance, AMD occurs. 81 In addition, innate immune cells such as macrophages, microglias, dendritic cells, and neutrophils are closely associated with the development of AMD, [82][83][84][85] but whether adaptive immunity has a role in AMD is highly debated. 86 Inflammatory responses contribute to both dry and wet AMD through different mechanisms.…”

Section: Inflammation and Amdmentioning

confidence: 99%

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

Ren¹,

Ren²,

Deng³

et al. 2022

JIR

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a blinding eye disease, whose incidence strongly increases with ages. The etiology of AMD is complex, including aging, abnormal lipid metabolism, chronic inflammation and oxidative stress. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for ocular structures and functions. This review summarizes the regulatory effects of LCPUFA on inflammation in AMD. LCPUFA are related to aging, autophagy and chronic inflammation. They are metabolized to pro-and anti-inflammatory metabolites by various enzymes. These metabolites stimulate inflammation in response to oxidative stress, causing innate and acquired immune responses. This review also discusses the possible clinical applications, which provided novel targets for the prevention and treatment of AMD and other age-related diseases.

show abstract

Section: Inflammation and Amdmentioning

confidence: 99%

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

Ren¹,

Ren²,

Deng³

et al. 2022

JIR

View full text Add to dashboard Cite

show abstract

“…Choroidal mast cells, with their unique position in the choroid and their dynamic release of bioactive mediators, are likely active participants in the progression of inflammatory and degenerative conditions [ 12 , 26 ]. Other studies further solidify this viewpoint by elucidating the mast cell’s potential in exacerbating oxidative stress, inflammation, and cellular damage in the ocular environment [ 27 , 36 , 119 ].…”

Section: Discussionmentioning

confidence: 99%

“…Clare et al [ 36 ] reported that mast cell activity contributes to the pathogenesis of retinal diseases by promoting inflammation and oxidative stress. They found that mast cells can be activated by oxidative stress, leading to the release of pro-inflammatory mediators.…”

Section: Choroidal Mast Cells and Amdmentioning

confidence: 99%

Choroidal Mast Cells and Pathophysiology of Age-Related Macular Degeneration

Malih,

Song,

Sorenson

et al. 2023

Cells

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast cells, with important roles in immune and allergic responses. Here, we will review what is known regarding the pathophysiology of AMD and expand on the recently proposed intricate roles of choroidal mast cells and their activation in outer retinal degeneration and AMD pathogenesis. We will focus on choroidal mast cell activation, the release of their bioactive mediators, and potential impact on ocular oxidative stress, inflammation, and overall retinal and choroidal health. We propose an important role for thrombospondin-1 (TSP1), a major ocular angioinflammatory factor, in regulation of choroidal mast cell homeostasis and activation in AMD pathogenesis. Drawing from limited studies, this review underscores the need for further comprehensive studies aimed at understanding the precise roles changes in TSP1 levels and choroidal mast cell activity play in pathophysiology of AMD. We will also propose potential therapeutic strategies targeting these regulatory pathways, and highlighting the promise they hold for curbing AMD progression through modulation of mast cell activity. In conclusion, the evolving understanding of the role of choroidal mast cells in AMD pathogenesis will not only offer deeper insights into the underlying mechanisms but will also offer opportunities for development of novel preventive strategies.

show abstract

“…IL-33 is an innate immunomodulatory cytokine that belongs to the IL-1 cytokine family and resides within the nuclei of various cell types ( Clare et al, 2021 ; Liew et al, 2016 ; Schmitz et al, 2005 ). Under cellular and tissue homeostasis, endogenous IL-33 negatively affects gene transcription as a nuclear protein in an intracrine fashion by sequestration of NF-κB, leading to the repression of gene expression to dampen pro-inflammatory pathways ( Martin and Martin, 2016 ; Ali et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Augustine,

Pavlou,

Harkin

et al. 2023

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Diabetic retinopathy (DR) is characterised by dysfunction of the retinal neurovascular unit, leading to visual impairment and blindness. Müller cells are key components of the retinal neurovascular unit and diabetes has a detrimental impact on these glial cells, triggering progressive neurovascular pathology of DR. Amongst many factors expressed by Müller cells, interleukin-33 (IL-33) has an established immunomodulatory role, and we investigated the role of endogenous IL-33 in DR. The expression of IL-33 in Müller cells increased during diabetes. Wild-type and Il33−/− mice developed equivalent levels of hyperglycaemia and weight loss following streptozotocin-induced diabetes. Electroretinogram a- and b-wave amplitudes, neuroretina thickness, and the numbers of cone photoreceptors and ganglion cells were significantly reduced in Il33−/− diabetic mice compared with those in wild-type counterparts. The Il33−/− diabetic retina also exhibited microglial activation, sustained gliosis, and upregulation of pro-inflammatory cytokines and neurotrophins. Primary Müller cells from Il33−/− mice expressed significantly lower levels of neurotransmitter-related genes (Glul and Slc1a3) and neurotrophin genes (Cntf, Lif, Igf1 and Ngf) under high-glucose conditions. Our results suggest that deletion of IL-33 promotes inflammation and neurodegeneration in DR, and that this cytokine is critical for regulation of glutamate metabolism, neurotransmitter recycling and neurotrophin secretion by Müller cells.

show abstract

Unravelling the therapeutic potential of IL-33 for atrophic AMD

Cited by 7 publications

References 94 publications

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

Choroidal Mast Cells and Pathophysiology of Age-Related Macular Degeneration

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Contact Info

Product

Resources

About