Systemic diseases and the cornea

Shah, Ruchi; Amador, Cynthia; Tormanen, Kati; Ghiam, Sean; Saghizadeh, Mehrnoosh; Arumugaswami, Vaithi; Kumar, Ashok; Kramerov, Andrei A.; Ljubimov, Alexander V.

doi:10.1016/j.exer.2021.108455

Cited by 49 publications

(31 citation statements)

References 560 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent publication also suggests that Rhesus macaques can be effectively infected with SARS-CoV-2 via the ocular surface, specifically through the conjunctival route [ 20 ]. In our previous study, we have shown the presence of SARS-CoV-2 in the postmortem corneal and scleral tissues of COVID-19 affected donors by qPCR and immunofluorescence analysis [ 13 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

et al. 2022

Self Cite

View full text Add to dashboard Cite

Purpose SARS-CoV-2 RNA has been detected in ocular tissues, but their susceptibility to SARS-CoV-2 infection is unclear. Here, we tested whether SARS-CoV-2 can infect human conjunctival epithelial cells (hCECs) and induce innate immune response. Methods Conjunctival tissue from COVID-19 donors was used to detect SARS-CoV-2 spike and envelope proteins. Primary hCECs isolated from cadaver eyes were infected with the parental SARS-CoV-2 and its beta variant of concern (VOC). Viral genome copy number, expression of viral entry receptors, TLRs, interferons, innate immune response genes was determined by qPCR. Viral receptors were examined in hCECs and tissue sections by immunostaining. Spike protein was detected in the cell culture supernatant by dot blot. Results Spike and envelope proteins were found in conjunctiva from COVID-19 patients. SARS-CoV-2 infected hCECs showed high viral copy numbers at 24–72h post-infection; spike protein levels were the highest at 24hpi. Viral entry receptors ACE2, TMPRSS2, CD147, Axl, and NRP1 were detected in conjunctival tissue and hCECs. SARS-CoV-2 infection-induced receptor expression at early time points post-infection, but gene expression of most TLRs peaked at 48 or 72hpi. SARS-CoV-2 infected hCECs showed higher expression of genes regulating antiviral response, RIG-I , interferons (α, β, & λ), ISG15 & OAS2 , cytokines ( IL-6, IL1β, TNFα ), and chemokines ( CXCL10, CCL5 ). Compared to the parental strain, beta VOC induced increased viral copy number and innate response in hCECs. Conclusions Conjunctival epithelial cells are susceptible to SARS-CoV-2 infection. Beta VOC is more infectious than the parental strain and evokes a higher antiviral and inflammatory response.

show abstract

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Diabetic keratopathy (DK) is caused by diabetes-associated hyperglycaemia (a persistent high-glucose state in blood in general) and manifests as persistent corneal epithelial erosion, superficial punctate keratopathy, delayed epithelial regeneration, and reduced corneal sensitivity, which may cause impaired vision or permanent vision loss [ 12 ]. Dry eye disease (DED) is a multifactorial and chronic disease characterized by tear deficiency and/or evaporative dry eye, and causes the tear film covering the CE to adopt a local hyperosmotic state, which causes damage to the CE and delayed wound healing [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Zhang

et al. 2022

Cell Death Dis

View full text Add to dashboard Cite

Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

show abstract

“…It is known that corneal transparency requires expression of proper cytokeratins by the epithelia ( Shah et al., 2021 ). We tested expression of several keratins in Notch1 -deficient and control mice.…”

Section: Resultsmentioning

confidence: 99%

“…The cornea provides about two-thirds of the eye’s focusing power and acts as a barrier to protect the underlying tissues from damage ( Shah et al., 2021 ; Sugioka et al., 2021 ). Mammalian cornea consists primarily of three layers: an outer non-keratinized squamous epithelium layer ( Nowell and Radtke, 2017 ), a stroma layer at the middle with collagen-rich matrix and interspersed keratocytes (corneal stromal cells/fibroblasts), which provides strength to the cornea ( Espana and Birk, 2020 ; Fukuda, 2020 ; Lagali, 2020 ; Medeiros et al., 2018 ; Yam et al., 2020 ), and an inner endothelial layer, which maintains hydration of the cornea ( Faye et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Systemic diseases and the cornea

Cited by 49 publications

References 560 publications

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

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

Notch1 signaling in keratocytes maintains corneal transparency by suppressing VEGF expression

Contact Info

Product

Resources

About