Pyroptosis in pterygium pathogenesis

Sun, Naiyu; Zhang, Hong

doi:10.1042/bsr20180282

Cited by 19 publications

(12 citation statements)

References 39 publications

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“…In the conjunctiva, NLRP3 was observed at constitutive levels in healthy humans [86,87] and rat [87] tissues. Diseases such as Mooren's ulcer [86] and pterygium [88] were found to elevate NLRP3 levels. Cultured human and rat goblet cells were also reported to increase NLRP3 significantly following bacterial infection [87].…”

Section: Nod-like Receptors In the Ocular Tissuesmentioning

confidence: 99%

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Lim

Wieser

Ganga

et al. 2020

IJMS

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Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.

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Section: Nod-like Receptors In the Ocular Tissuesmentioning

confidence: 99%

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Lim

Wieser

Ganga

et al. 2020

IJMS

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“…Unlike other cell death modes, pyroptosis is characterized by NLRP3 inflammasome-promoted and caspase-1-dependent plasma membrane rupture and release of DAMPs and cytokines such as IL-1β and IL-18 into the extracellular milieu, leading to sterile inflammation 22,23,25–31 . Pyroptosis-induced sterile inflammation has been associated with a variety of disorders 22,23,25,26 . We hypothesize that pyroptosis occurs in the trophoblast layer of the PE placenta, which may contribute to release of alarmins for systemic manifestation of the PE syndrome.…”

Section: Introductionmentioning

confidence: 99%

Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors

et al. 2019

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Systemic manifestation of preeclampsia (PE) is associated with circulating factors, including inflammatory cytokines and damage-associated molecular patterns (DAMPs), or alarmins. However, it is unclear whether the placenta directly contributes to the increased levels of these inflammatory triggers. Here, we demonstrate that pyroptosis, a unique inflammatory cell death pathway, occurs in the placenta predominantly from early onset PE, as evidenced by elevated levels of active caspase-1 and its substrate or cleaved products, gasdermin D (GSDMD), IL-1β, and IL-18. Using cellular models mimicking pathophysiological conditions (e.g., autophagy deficiency, hypoxia, and endoplasmic reticulum (ER) stress), we observed that pyroptosis could be induced in autophagy-deficient human trophoblasts treated with sera from PE patients as well as in primary human trophoblasts exposed to hypoxia. Exposure to hypoxia elicits excessive unfolded protein response (UPR) and ER stress and activation of the NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome in primary human trophoblasts. Thioredoxin-interacting protein (TXNIP), a marker for hyperactivated UPR and a crucial signaling molecule linked to NLRP3 inflammasome activation, is significantly increased in hypoxia-treated trophoblasts. No evidence was observed for necroptosis-associated events. Importantly, these molecular events in hypoxia-treated human trophoblasts are significantly observed in placental tissue from women with early onset PE. Taken together, we propose that placental pyroptosis is a key event that induces the release of factors into maternal circulation that possibly contribute to severe sterile inflammation and early onset PE pathology.

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“…Regarding cytokines, many studies have depicted the relationship between IL-6 and pterygia. Sun and Chang also described significantly higher IL-18 levels in pterygia compared with those in a normal conjunctiva 13,14 . In contrast, IL-6 and IL-18 concentrations in the pterygium group did not significantly differ from those of the HCs, and binary logistic regression controlling for the Schirmer I test as a confounding factor showed that the IL-6 and IL-18 covariates did not significantly differ between the HC and pterygium groups.…”

Section: Pterygium and Tear Cytokine Concentrationsmentioning

confidence: 90%

“…Because of the uncertainty of the pterygium pathogenesis, a review analyzed several cytokines involved in pterygium fibrovascular growth, especially vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-18 13 , 14 . The relationship of these cytokines with the pterygium pathogenesis is interesting.…”

Section: Introductionmentioning

confidence: 99%

Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

Uthaithammarat

Kasetsuwan

Chongpison

et al. 2021

Sci Rep

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This study evaluated human papillomavirus’s (HPV) role in pterygium pathogenesis, its autoinoculation from genitalia to ocular surface, potential cytokines involved, and crosstalk cytokines between pterygium and dry eye (DE). This cross-sectional study enrolled 25 healthy controls (HCs) and 116 pterygium patients. Four subgroups of pterygium and DE were used in cytokine evaluations. Conjunctival and pterygium swabs and first-void urine samples (i.e., genitalia samples) were collected for HPV DNA detection using real-time polymerase chain reaction. Tear cytokines interleukin (IL)-6, IL-18, and vascular endothelial growth factor (VEGF) in tears were evaluated. No HPV DNA was detected in conjunctival or pterygium swabs. No association was found between HPV DNA in urine samples and that from conjunctival or pterygium swabs. Tear VEGF levels were significantly higher in pterygium patients than in HCs, with no markedly different levels between primary and recurrent pterygia. Tear IL-6, IL-18, and tear VEGF were significantly higher in participants with DE, regardless of pterygium status. In conclusion, HPV infection was not a pathogenic factor of pterygia. The hypothesis of HPV transmitting from the genitals to ocular surfaces was nullified. Tear VEGF was involved in both pterygia and DE, whereas tear IL-6 and IL-18 played roles only in DE.

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Pyroptosis in pterygium pathogenesis

Cited by 19 publications

References 39 publications

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors

Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

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