Background: Age-related changes affecting the ocular surface cause vision loss in the elderly. Cisd2 deficiency drives premature aging in mice as well as resulting in various ocular surface abnormalities. Here we investigate the role of CISD2 in corneal health and disease.
Methods: We studied the molecular mechanism underlying the ocular phenotypes brought about by Cisd2 deficiency using both Cisd2 knockout (KO) mice and a human corneal epithelial cell (HCEC) cell line carrying a CRISPR-mediated CISD2KO background. We also develop a potential therapeutic strategy that targets the Ca signaling pathway, which has been found to be dysregulated in the corneal epithelium of subjects with ocular surface disease in order to extend the mechanistic findings into a translational application.
Findings: Firstly, in patients with corneal epithelial disease, CISD2 is down-regulated in their corneal epithelial cells. Secondly, using mouse cornea, Cisd2 deficiency causes a cycle of chronic injury and persistent repair resulting in exhaustion of the limbal progenitor cells. Thirdly, in human corneal epithelial cells, CISD2 deficiency disrupts intracellular Ca homeostasis, impairing mitochondrial function, thereby retarding corneal repair. Fourthly, cyclosporine A and EDTA facilitate corneal epithelial wound healing in Cisd2 knockout mice. Finally, cyclosporine A treatment restores corneal epithelial erosion in patients with dry eye disease, which affects the ocular surface.
Interpretation: These findings reveal that Cisd2 plays an essential role in the cornea and that Ca signaling pathways are potential targets for developing therapeutics of corneal epithelial diseases.
Funding: This study was supported by the Ministry of Science and Technology (MOST) and Chang Gung Medical Research Foundation, Taiwan.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577409 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2021.103654 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy.
Mater Today Bio
February 2025
Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China.
Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model for the first time, incorporating corneal epithelial cells, stromal cells, endothelial cells, and nerves to simulate DK conditions .
View Article and Find Full Text PDFDestructive and Protective Effects and Therapeutic Targets of IL-36 Family Cytokines in Dry Eye Disease.
Ocul Surf
January 2025
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, 77030 United States. Electronic address:
Purpose: To explore the destructive and protective effects and therapeutic targets of IL-36 cytokines in dry eye disease using a murine dry eye model.
Methods: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls. A topical challenge model was performed in normal mice with exogenous rmIL-36α, rhIL-38 and 2% ectoine, or PBS vehicle.
Y-27632 and dual media culture approach promote the construction and transplantation of rabbit limbal epithelial cell sheets via cell spheroid culture and auto-bioprinting.
Acta Biomater
January 2025
Ophthalmology Department, The First Affiliated Hospital of Jinan University, Guangzhou, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China; Institute of Ophthalmology, Medical College, Jinan University, Guangzhou, China; Aier School of Ophthalmology, Central South University, Changsha, China. Electronic address:
The shortage of corneal donors and the limitations in tissue engineering grafts, such as biocompatibility and mechanical properties, pose significant challenges in corneal transplantation. Here, for the first time, we investigate the effect of Rho kinase inhibitor Y-27632 and a dual media culture approach, including proliferative media (M1) and stabilizing media (M2), on rabbit limbal epithelial stem cells (LESCs), aiming to explore the feasibility of constructing corneal cell sheets in vitro through auto-bioprinting and assessing their corneal wound healing capacity in vivo. Y-27632 has primarily demonstrated significantly enhanced LESCs growth, proliferation, and reduced apoptosis.
View Article and Find Full Text PDF3D Printed Biomimetic Bilayer Limbal Implants for regeneration of the Corneal Structure in Limbal Stem Cell Deficiency.
Acta Biomater
January 2025
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China. Electronic address:
Limbal stem cell deficiency (LSCD) causes vision loss and is often treated by simple corneal epithelial cell transplantation with poor long-term efficiency. Here, we present a biomimetic bilayer limbal implant using digital light processing 3D printing technology with gelatin methacrylate (GelMA) and poly (ethylene glycol) diacrylate (PEGDA) bioinks containing corneal epithelial cells (CECs) and corneal stromal stem cells (CSSCs), which can transplant CECs and improve the limbal niche simultaneously. The GelMA/PEGDA hydrogel possessed robust mechanical properties to support surgical transplantation and had good transparency, suitable swelling and degradation rate as a corneal implant.
View Article and Find Full Text PDFEnhancing Corneal Sensitivity in Diabetic Patients Through an Innovative Ophthalmic Solution: In Vivo and Vitro Results.
J Clin Med
January 2025
Department of Sciences, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy.
: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution's impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!