Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms

Pang, Kunpeng; Lennikov, Anton; Yang, Menglu

doi:10.1002/ame2.12192

Cited by 23 publications

(19 citation statements)

References 65 publications

(144 reference statements)

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“…As an avascular tissue, the cornea is unique in consumption by acquiring oxygen from the atmosphere and is sensitive to the oxygen concentration change (Pang et al, 2021). Hypoxia caused by the contact lens wearing, inflammation, wounds and infections, results in the disruption of corneal epithelial barrier function, delay of the wound healing, alteration of the extracellular matrix, and leads to corneal neovascularization and opacity (Lee et al, 2020;Onochie et al, 2020;Bai et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis

Zhu

Shan²,

Li³

et al. 2022

Front. Pharmacol.

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Transdifferentiation of keratocytes into fibroblasts or further into myofibroblasts, which produced denser and more disorganized extracellular matrix, is the major cause of corneal fibrosis and scarring, leading to corneal blindness. TGF-β1 is the critical cytokine for the myofibroblast’s transdifferentiation and survival. Hypoxia Inducible Factor (HIF) was found to play an important role in promoting fibrosis in lung, kidney, and dermal tissues recently. Our preliminary study demonstrated that topical administration of the acriflavine (ACF), a drug inhibiting HIF dimerization, delayed corneal opacity and neovascularization after the alkali burn. To know whether ACF could prevent corneal fibrosis and improve corneal transparency, we created a mouse mechanical corneal injury model and found that topical administration of ACF significantly inhibited corneal fibrosis at day 14 post-injury. The reduction of myofibroblast marker α-SMA, and fibronectin, one of the disorganized extracellular matrix molecules, in the corneal stroma were confirmed by the examination of immunohistochemistry and real-time PCR. Furthermore, the ACF inhibited the expression of α-SMA and fibronectin in both TGF-β1 stimulated or unstimulated fibroblasts in vitro. This effect was based on the inhibition of HIF signal pathways since the levels of the HIF-1α downstream genes including Slc2a1, Bnip3 and VEGFA were downregulated. To our knowledge, this is the first time to implicate that HIFs might be a new treatment target for controlling corneal fibrosis in mechanical corneal injuries.

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Section: Introductionmentioning

confidence: 99%

Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis

Zhu

Shan²,

Li³

et al. 2022

Front. Pharmacol.

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“…Hypoxia triggers a multitude of cellular and molecular changes to adapt to the lack of oxygen, particularly activating the hypoxia-inducible factor (Hif) signaling pathways 31 . While this pathway has been well studied in multiple systems, its role in the cornea is less clear 32 . In the current study, we found that alkali burn induces Hif-1α activation at 1- and 7-day post burn in the cornea and conjunctiva, and that SSOE treatment effectively inhibits this activation at 1 day but not 7-day.…”

Section: Discussionmentioning

confidence: 99%

Perfluorodecalin-based oxygenated emulsion as a topical treatment for chemical burn to the eye

Pang

Zhu

et al. 2022

Nat Commun

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Chemical injuries to the eye are emergencies with limited acute treatment options other than prompt irrigation and can cause permanent vision loss. We developed a perfluorodecalin-based supersaturated oxygen emulsion (SSOE) to topically deliver high concentration of oxygen to the eye. SSOE is manufactured in hyperbaric conditions and stored in a ready-to-use canister. Upon dispensation, SSOE rapidly raises partial oxygen pressure 3 times over atmospheric level. SSOE is biocompatible with human corneal cells and safe on mouse eyes in vivo. A single topical application of SSOE to the eye after alkali injury significantly promotes corneal epithelial wound healing, decreases anterior chamber exudation, and reduces optical opacity and cataract formation in mice. SSOE treatment reduces intraocular hypoxia, cell death, leukocyte infiltration, production of inflammatory mediators, and hypoxia-inducible factor 1-alpha signaling, thus hastening recovery of normal tissue integrity during the wound healing process. Here, we show that SSOE is an effective topical therapeutic in the acute treatment of ocular chemical injuries.

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“…From a metabolic point of view, the absence of nutrients from the blood and vitreous associated with hypoxia leads to alterations in the corneal tissues and the level of the aqueous and vitreous humor [ 31 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Eyelid Position and Environmental Conditions on the Corneal Changes in Early Postmortem Interval: A Prospective, Multicentric OCT Study

et al. 2022

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In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant.

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Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms

Cited by 23 publications

References 65 publications

Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis

Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis

Perfluorodecalin-based oxygenated emulsion as a topical treatment for chemical burn to the eye

The Influence of Eyelid Position and Environmental Conditions on the Corneal Changes in Early Postmortem Interval: A Prospective, Multicentric OCT Study

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