scholarly journals Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 5172 ◽  
Author(s):  
Mary Ann Stepp ◽  
Sonali Pal-Ghosh ◽  
Gauri Tadvalkar ◽  
Cintia S. de Paiva
Keyword(s):  
Cell Proliferation ◽  
Ocular Surface ◽  
Corneal Epithelial Cell ◽  
Corneal Sensitivity ◽  
Corneal Epithelial ◽  
Female Mice ◽  
Axon Density ◽  
Age Related ◽  
Corneal Nerves ◽  
The Impact

Aging impacts the ocular surface and reduces intraepithelial corneal nerve (ICN) density in male and female mice. Many researchers use retired breeders to study naturally aged female mice. Yet, the impact of parity and the length of time since breeders were retired on age-related changes in the intraepithelial corneal nerves is not known. Here we study 2 month (M) nulliparous (NP) females as well as 9M, 10M, and 11M NP and multiparous (MP) female mice to determine whether parity impacts the age-related decline seen in corneal axon density; 9M male mice are also included in these assessments. After showing that parity attenuates age-related loss in axon density, we also assess the impact of parity on corneal epithelial cell proliferation and find that it impacts cell proliferation and axon density normalized by cell proliferation. Stromal nerve arborization is also impacted by aging with parity enhancing stromal nerves in older mice. qPCR was performed on 20 genes implicated in ICN density using corneal epithelial RNA isolated from 10M NP and MP mice and showed that NGF expression was significantly elevated in MP corneal epithelium. Corneal sensitivity was significantly higher in 9M MP mice compared to NP mice and increased sensitivity in MP mice was accompanied by increased nerve terminals in the apical and middle cell layers. Together, these data show that parity in mice attenuates several aspects of the age-related decline seen on the ocular surface by retaining sensory axons and corneal sensitivity as mice age.

scholarly journals Utilization of metabolic energy in treatment of ocular surface disorders: polyphosphate as an energy source for corneal epithelial cell proliferation

RSC Advances ◽  
2019 ◽  
Vol 9 (39) ◽  
pp. 22531-22539 ◽  
Author(s):  
Adrian Gericke ◽  
Xiaohong Wang ◽  
Maximilian Ackermann ◽  
Meik Neufurth ◽  
Matthias Wiens ◽  
...  
Keyword(s):  
Energy Source ◽  
Cell Proliferation ◽  
Ocular Surface ◽  
Clinical Problem ◽  
Metabolic Energy ◽  
Corneal Epithelial Cell ◽  
Epithelial Cell Proliferation ◽  
Corneal Epithelial ◽  
Ocular Surface Diseases ◽  
Major Clinical Problem

Impaired regeneration of the corneal epithelium, as found in many ocular surface diseases, is a major clinical problem in ophthalmology.

scholarly journals The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells

Glycobiology ◽  
2020 ◽  
Vol 30 (11) ◽  
pp. 872-880 ◽  
Author(s):  
Nicole M McColgan ◽  
Marissa N Feeley ◽  
Ashley M Woodward ◽  
Damien Guindolet ◽  
Pablo Argüeso
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Ocular Surface ◽  
Barrier Function ◽  
Terminal Differentiation ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Human Corneal Epithelial Cells ◽  
Glcnac Transferase

Abstract Dynamic modification of nuclear and cytoplasmic proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) plays an important role in orchestrating the transcriptional activity of eukaryotic cells. Here, we report that the O-GlcNAc modification contributes to maintaining ocular surface epithelial homeostasis by promoting mucin biosynthesis and barrier function. We found that induction of human corneal epithelial cell differentiation stimulated the global transfer of O-GlcNAc to both nuclear and cytosolic proteins. Inflammatory conditions, on the other hand, were associated with a reduction in the expression of O-GlcNAc transferase at the ocular surface epithelia. Loss- and gain-of-function studies using small interfering RNA targeting O-GlcNAc transferase, or Thiamet G, a selective inhibitor of O-GlcNAc hydrolase, respectively, revealed that the presence of O-GlcNAc was necessary to promote glycocalyx barrier function. Moreover, we found that Thiamet G triggered a correlative increase in both surface expression of MUC16 and apical epithelial cell area while reducing paracellular permeability. Collectively, these results identify intracellular protein O-glycosylation as a novel pathway responsible for promoting the terminal differentiation of human corneal epithelial cells.

scholarly journals The impact of IGF1R SNPs on susceptibility to age-related cataract

2019 ◽  
Author(s):  
Yilei Cui ◽  
Xiaoning Yu ◽  
Xin Zhang ◽  
Yelei Tang ◽  
Xiajing Tang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Chinese Population ◽  
Caspase 3 ◽  
S Phase ◽  
Han Chinese ◽  
Human Lens ◽  
Han Chinese Population ◽  
Age Related ◽  
The Impact

Abstract Background: The insulin-like growth factor 1 receptor (IGF1R) gene is essential for lens development, but the impact of IGF1R on age-related cataract(ARC) has not been investigated. This study explored the association between IGF1R single nucleotide polymorphism (SNP) and ARC susceptibility ,and uncover the underlying mechanism in human lens epithelial (HLE) cells. Methods:A total of 1190 unrelated participants ,comprising 690 ARC patients and 550 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The X2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, in the IGF1R knockdown HLE cells, cell proliferation was detected via CCK-8 analysis. Cell cycle and apoptosis were evaluated by flow cytometry,while the expression of cycle- and apoptosis-related molecules were determined via Q-PCR and Western blot. The Caspase-3 activity was measured using its assay kit. Results: The rs1546713 in IGF1R gene was identified（P =0.046，OR：1.606，CI：1.245,2.071）,which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrest at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclinA , cyclinB, cyclinE and P21,while the pro-apoptosis function was related to stimulate the activation of Caspase-3 activities and the alteration of Caspase-3,Bcl-2 and Bax expression levels. Conclusions: This study first reported that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provided new clues to understanding the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

scholarly journals TLR4-Dependent DUOX2 Activation Triggered Oxidative Stress and Promoted HMGB1 Release in Dry Eye

2022 ◽  
Vol 8 ◽  
Author(s):  
Bowen Wang ◽  
Hao Zeng ◽  
Xin Zuo ◽  
Xue Yang ◽  
Xiaoran Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Dry Eye ◽  
Ocular Surface ◽  
Cell Counting ◽  
Corneal Epithelial Cell ◽  
Rna Seq ◽  
Corneal Epithelial ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Dry eye disease (DED) is one of the most common ocular surface diseases worldwide. DED has been characterized by excessive accumulation of reactive oxygen species (ROS), following significant corneal epithelial cell death and ocular surface inflammation. However, the key regulatory factor remains unclear. In this study, we tended to explore whether DUOX2 contributed to DED development and the underlying mechanism. Human corneal epithelial (HCE) cells were treated with hyperosmolarity, C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Expression of mRNA was investigated by RNA sequencing (RNA-seq) and quantitative real-time PCR (qPCR). Protein changes and distribution of DUOX2, high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), and 4-hydroxynonenal (4-HNE) were evaluated by western blot assays and immunofluorescence. Cell death was assessed by Cell Counting Kit-8 (CCK8), lactate dehydrogenase (LDH) release, and propidium iodide (PI) staining. Cellular ROS levels and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. RNA-seq and western blot assay indicated a significant increase of DUOX2 dependent of TLR4 activation in DED both in vitro and in vivo. Immunofluorescence revealed significant translocation of HMGB1 within corneal epithelial cells under hyperosmolar stress. Interestingly, after ablated DUOX2 expression by siRNA, we found a remarkable decrease of ROS level and recovered MMP in HCE cells. Moreover, knockdown of DUOX2 greatly inhibited HMGB1 release, protected cell viability and abolished inflammatory activation. Taken together, our data here suggest that upregulation of DUOX2 plays a crucial role in ROS production, thereafter, induce HMGB1 release and cell death, which triggers ocular surface inflammation in DED.

scholarly journals Rho kinases regulate corneal epithelial wound healing

2008 ◽  
Vol 295 (2) ◽  
pp. C378-C387 ◽  
Author(s):  
Jia Yin ◽  
Fu-Shin X. Yu
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Migration ◽  
Rho Gtpase ◽  
Adhesion Formation ◽  
Small Gtpase ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Rho Kinases

We have previously shown that Rho small GTPase is required for modulating both cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding. In the present study, we investigated the role of Rho kinases (ROCKs), major effectors of Rho GTPase, in mediating corneal epithelial wound healing. Both ROCK 1 and 2 were expressed and activated in THCE cells, an SV40-immortalized human corneal epithelial cell (HCEC) line, in response to wounding, lysophosphatidic acid, and heparin-binding EGF-like growth factor (HB-EGF) stimulations. The ROCK inhibitor Y-27632 efficiently antagonized ROCK activities without affecting Rho activation in wounded HCECs. Y-27632 promoted basal and HB-EGF-enhanced scratch wound healing and enhanced cell migration and adhesion to matrices, while retarded HB-EGF induced cell proliferation. E-cadherin- and β-catenin-mediated cell-cell junction and actin cytoskeleton organization were disrupted by Y-27632. Y-27632 impaired the formation and maintenance of tight junction barriers indicated by decreased trans-epithelial resistance and disrupted occludin staining. We conclude that ROCK activities enhance cell proliferation, promote epithelial differentiation, but negatively modulate cell migration and cell adhesion and therefore play a role in regulating corneal epithelial wound healing.

Sign in / Sign up

Export Citation Format

Share Document