Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal

Singh, Mahavir; Tyagi, Suresh C.

doi:10.1016/j.mehy.2017.06.012

Cited by 13 publications

(7 citation statements)

References 52 publications

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“…Thus, pyroptosis and inflammation are relevant to our understanding of their effects during serious medical conditions for which inflammation is central to the pathophysiology of diseases such as DR. In fact, DR shares many similarities with other inflammatory diseases and as a result it is being recognized now as the central player in DR via various mechanisms including pyroptosis ( Joussen et al, 2001 ; Singh and Tyagi, 2017b ).…”

Section: Inflammation and Pyroptosis Disrupt Physiological Homeostasimentioning

confidence: 99%

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis

et al. 2018

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Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells’ redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects.

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Section: Inflammation and Pyroptosis Disrupt Physiological Homeostasimentioning

confidence: 99%

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis

et al. 2018

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“…Obese adipocytes have been reported to overexpress NLRP3 inflammasome and undergo stress-induced pyroptosis (Giordano et al 2013). It is also predicted that pyroptosis may be a mode of cell death in HHcy mediated age-related macular degeneration (AMD), a disorder also prevalent among obese individuals (Adams et al 2011) (Singh and Tyagi 2017).…”

Section: Homocysteine and Obesitymentioning

confidence: 99%

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

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Majumder

Singh

et al. 2018

Can. J. Physiol. Pharmacol.

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Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu and Zn, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

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“…Pyroptosis, also known as cellular inflammatory necrosis, is a newly discovered form of cell death that is important to innate immune response. It is manifested by the continuous expansion of cells until the cell membrane ruptures, leading to the release of cellular contents and thus the activation of an intense inflammatory response ( 75 ). Cell death is dependent on caspase-1 and its PRR, NLR family pyrin domain containing 3 (NLRP3) inflammasome, which cleaves the inactive caspase-1 precursor to be active caspase-1 ( 76 ).…”

Section: Immunomodulation Of Dry Eye Diseasementioning

confidence: 99%

Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

et al. 2022

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Dry eye is currently one of the most common ocular surface disease. It can lead to ocular discomfort and even cause visual impairment, which greatly affects the work and quality of life of patients. With the increasing incidence of dry eye disease (DED) in recent years, the disease is receiving more and more attention, and has become one of the hot research fields in ophthalmology research. Recently, with the in-depth research on the etiology, pathogenesis and treatment of DED, it has been shown that defects in immune regulation is one of the main pathological mechanisms of DED. Since the non-specific and specific immune response of the ocular surface are jointly regulated, a variety of immune cells and inflammatory factors are involved in the development of DED. The conventional treatment of DED is the application of artificial tears for lubricating the ocular surface. However, for moderate-to-severe DED, treatment with anti-inflammatory drugs is necessary. In this review, the immunomodulatory mechanisms of DED and the latest research progress of its related treatments including Chinese medicine will be discussed.

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Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal

Cited by 13 publications

References 52 publications

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

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