Roles and Mechanisms of Regulated Necrosis in Corneal Diseases: Progress and Perspectives

Lin, Wanying; Chen, Minting; Cissé, Yacouba; Chen, Xiaofeng; Bai, Lipeng

doi:10.1155/2022/2695212

Cited by 4 publications

(2 citation statements)

References 99 publications

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“…The upregulated genes that overlapped in both the cornea and conjunctiva had primary associations to immune response, regulation of angiogenesis, and apoptotic signaling pathways. These pathways align with the known biological pathways of keratitis progression ( Zhou et al., 2010 ; Narimatsu et al., 2019 ; Shrestha et al., 2021 ; Lin et al., 2022 ).…”

Section: Discussionsupporting

confidence: 63%

Ocular surface immune transcriptome and tear cytokines in corneal infection patients

Alenezi,

Parnell,

Schibeci

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundMicrobial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions’ pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears.MethodsCorneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1β, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay.ResultsA total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) <−2 or > 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <−3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance.ConclusionsDuring corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight.

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Section: Discussionsupporting

confidence: 63%

Ocular surface immune transcriptome and tear cytokines in corneal infection patients

Alenezi,

Parnell,

Schibeci

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Ferroptosis has been studied in association with ischemia-reperfusion injury, kidney injury, cardiac diseases, and neurodegenerative diseases [ 18 , 19 ]. Its role in ocular diseases, such as corneal epithelial disease [ 20 ], dry eye [ 21 ], retinal pigment epithelial diseases [ 22 ], and glaucoma [ 23 ], has been recently investigated [ 24 ]. The association of ferroptosis with alkali corneal wound healing has also been studied.…”

Section: Introductionmentioning

confidence: 99%

A Novel Ferroptosis Inhibitor UAMC-3203, a Potential Treatment for Corneal Epithelial Wound

et al. 2022

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Corneal wound, associated with pain, impaired vision, and even blindness, is the most common ocular injury. In this study, we investigated the effect of a novel ferroptosis inhibitor, UAMC-3203 (10 nM–50 µM), in corneal epithelial wound healing in vitro in human corneal epithelial (HCE) cells and ex vivo using alkali-induced corneal wounded mice eye model. We evaluated in vivo acute tolerability of the compound by visual inspection, optical coherence tomography (OCT), and stereomicroscope imaging in rats after its application (100 µM drug solution in phosphate buffer pH 7.4) twice a day for 5 days. In addition, we studied the partitioning of UAMC-3203 in corneal epithelium and corneal stroma using excised porcine cornea. Our study demonstrated that UAMC-3203 had a positive corneal epithelial wound healing effect at the optimal concentration of 10 nM (IC50 value for ferroptosis) in vitro and at 10 µM in the ex vivo study. UAMC-3203 solution (100 µM) was well tolerated after topical administration with no signs of toxicity and inflammation in rats. Ex-vivo distribution study revealed significantly higher concentration (~12–38-fold) and partition coefficient (Kp) (~52 times) in corneal epithelium than corneal stroma. The UAMC-3203 solution (100 µM) was stable for up to 30 days at 4 °C, 37 °C, and room temperature. Overall, UAMC-3203 provides a new prospect for safe and effective therapy for corneal wounds.

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The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease

Asai,

Lee,

Sato

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Roles and Mechanisms of Regulated Necrosis in Corneal Diseases: Progress and Perspectives

Cited by 4 publications

References 99 publications

Ocular surface immune transcriptome and tear cytokines in corneal infection patients

Ocular surface immune transcriptome and tear cytokines in corneal infection patients

A Novel Ferroptosis Inhibitor UAMC-3203, a Potential Treatment for Corneal Epithelial Wound

The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease

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