The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Chen, Kuangqi; Li, Yanqing; Zhang, Xuhong; Ullah, Rahim; Tong, Jianping; Shen, Ye

doi:10.1038/s41419-022-04963-x

Cited by 83 publications

(34 citation statements)

References 125 publications

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“…Therefore, researchers often use animal diabetes models and in vitro cell models to study pathogenesis (78, 79). The changes in growth factors, immune cells and signal pathways in diabetic keratopathy have been elaborated in previous reviews (4,14,17,78,80). Here, we mainly discuss the following aspects.…”

Section: Pathologic Mechanismsmentioning

confidence: 93%

Mechanistic investigations of diabetic ocular surface diseases

et al. 2022

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With the global prevalence of diabetes mellitus over recent decades, more patients suffered from various diabetic complications, including diabetic ocular surface diseases that may seriously affect the quality of life and even vision sight. The major diabetic ocular surface diseases include diabetic keratopathy and dry eye. Diabetic keratopathy is characterized with the delayed corneal epithelial wound healing, reduced corneal nerve density, decreased corneal sensation and feeling of burning or dryness. Diabetic dry eye is manifested as the reduction of tear secretion accompanied with the ocular discomfort. The early clinical symptoms include dry eye and corneal nerve degeneration, suggesting the early diagnosis should be focused on the examination of confocal microscopy and dry eye symptoms. The pathogenesis of diabetic keratopathy involves the accumulation of advanced glycation end-products, impaired neurotrophic innervations and limbal stem cell function, and dysregulated growth factor signaling, and inflammation alterations. Diabetic dry eye may be associated with the abnormal mitochondrial metabolism of lacrimal gland caused by the overactivation of sympathetic nervous system. Considering the important roles of the dense innervations in the homeostatic maintenance of cornea and lacrimal gland, further studies on the neuroepithelial and neuroimmune interactions will reveal the predominant pathogenic mechanisms and develop the targeting intervention strategies of diabetic ocular surface complications.

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Section: Pathologic Mechanismsmentioning

confidence: 93%

Mechanistic investigations of diabetic ocular surface diseases

et al. 2022

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“…An imbalance between antioxidant defenses and ROS, produced in large part by mitochondria, induces oxidative stress [ 59 ]. Chen and colleagues in 2022 demonstrated an improvement in the effects of DED reversing hyperosmolarity-mediated mitochondrial dysfunction in HCE-2 [ 60 ]. For this reason, we focused our attention on mtROS levels.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Conventional and Hyaluronic Acid-Coated Thymoquinone Liposomes in an In Vitro Model of Dry Eye

et al. 2023

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Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of Nigella sativa L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.

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“…Inflammatory responses caused by diseases related to the ocular surface can directly damage the epithelial cells of the ocular surface ( 27 ). There is evidence that epithelial apoptosis is closely related to the occurrence of dry eye ( 28 , 29 ), but whether it is involved in the occurrence of GO is unclear. Our results showed that Caspase-3 levels in exosomes from GO patients were higher than those in exosomes from controls, while the levels of Caspase-3 in extraocular muscles in GO patients were significantly higher.…”

Section: Discussionmentioning

confidence: 99%

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

et al. 2022

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Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.

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The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates

Cited by 83 publications

References 125 publications

Mechanistic investigations of diabetic ocular surface diseases

Mechanistic investigations of diabetic ocular surface diseases

Evaluation of Conventional and Hyaluronic Acid-Coated Thymoquinone Liposomes in an In Vitro Model of Dry Eye

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

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