A highly selective inhibitor of discoidin domain receptor-1 (DDR1-IN-1) protects corneal epithelial cells from YAP/ACSL4-mediated ferroptosis in dry eye.

Background And Purpose: This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism.

Experimental Approach: Dry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7 days with DDR1-IN-1, a selective inhibitor of DDR1.

Integrative analysis of gene expression datasets in corneal endothelium samples of Fuchs endothelial corneal dystrophy.

FECD is an age-related progressive ocular disorder characterized by the gradual loss of corneal endothelial cells. Although the exact pathogenesis of FECD remains incompletely understood, differentially expressed genes in the corneal endothelium of FECD patients compared to controls have been reported in several studies. However, a consensus regarding consistently affected genes in FECD has not been established.

WNT16b promotes the proliferation and self-renewal of human limbal epithelial stem/progenitor cells via activating the calcium/calcineurin A/NFATC2 pathway.

Our previous finding revealed that WNT16b promoted the proliferation of human limbal epithelial stem cells (hLESCs) through a β-catenin independent pathway. Here, we aimed to explore its underlying molecular mechanism and evaluate its potential in the treatment of limbal stem cell deficiency (LSCD). Based on the findings of mRNA-sequencing, the expression of key molecules in WNT/calcineurin A/NFATC2 signalling pathway was investigated in WNT16b-co-incubated hLESCs and control hLESCs.

Mitochondria-associated endoplasmic reticulum membranes dysfunction contributes to PARP-1-dependent cell death under oxidative stress in retinal precursor cells.

Persistent poly (ADP-ribose) polymerase 1 (PARP-1) activation has proven detrimental and can lead to PARP-1-dependent cell death. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) serve as essential hubs for many biological pathways, such as autophagy and mitochondria fission and fusion. This study aimed to alleviate the effects of hydrogen peroxide (H O )-induced persistent PARP-1 activation and MAM dysregulation by the usage of a PARP-1 inhibitor.

Olaparib, a PARP-1 inhibitor, protects retinal cells from ocular hypertension-associated oxidative damage.

Glaucoma is the most common cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) and relative hypoxia in the retina stimulate the production of reactive oxygen species (ROS), which, in turn, puts the retina and optic nerve under chronic oxidative stress. Emerging evidence has shown that oxidative stress can trigger PARP-1 overactivation, mitochondrial-associated endoplasmic reticulum membrane (MAM) dysregulation, and NLRP3 activation.

WNT16B enhances the proliferation and self-renewal of limbal epithelial cells via CXCR4/MEK/ERK signaling.

Culture of limbal epithelial cells (LECs) provides the principal source of transplanted limbal stem cells (LESCs) for treatment of limbal-stem-cell deficiency. Optimization of the culture conditions for in-vitro-expanded LECs will help to create a graft with an optimized quality and quantity of LESCs. This study aimed to investigate the effects of WNT16B on LECs and corneal wound healing and the underlying mechanism.

WAY-100635 Alleviates Corneal Lesions Through 5-HT Receptor-ROS-Autophagy Axis in Dry Eye.

To explore whether 5-HT receptors are involved in the dry eye disease (DED) mouse model and reveal its underlying mechanism. A C57BL/6J mouse DED model was established via the administration of 0.2% benzalkonium chloride twice a day for 14 days.

Long Non-coding RNAs Gabarapl2 and Chrnb2 Positively Regulate Inflammatory Signaling in a Mouse Model of Dry Eye.

To elucidate the expression profile and the potential role of long non-coding ribonucleic acids (RNAs) (lncRNAs) in a dry eye disease (DED) model. A DED model was established in C57BL/6J mice with 0.2% benzalkonium chloride (BAC) twice a day for 14 days.

Blockage of P2X7R suppresses Th1/Th17-mediated immune responses and corneal allograft rejection via inhibiting NLRP3 inflammasome activation.

P2X7R is a vital modifier of various inflammatory and immune-related diseases. However, the immunomodulatory effects of P2X7R on corneal allograft rejection remains unknown. Here we showed that P2X7R expression was significantly upregulated in corneal grafts of allogeneic transplant mice.

Therapeutic Nanoparticles from Grape Seed for Modulating Oxidative Stress.

The therapeutic potential of nanomaterials toward oxidative damage relevant diseases has attracted great attentions by offering promising advantages compared with conventional antioxidants. Although different kinds of nanoantioxidants have been well developed, the facile fabrication of robust and efficient nanoscavengers is still met with challenges like the use of toxic and high-cost subunits, the involvement of multistep synthetic process, and redundant purification work. Herein, a direct fabrication strategy toward polyphenol nanoparticles with tunable size, excellent biocompatibility, and reactive oxygen species (ROS) scavenging capacities from grape seed via an enzymatic polymerization method is reported.

Whole exome sequencing identified FAM149A as a plausible causative gene for congenital hereditary endothelial dystrophy, affecting Nrf2-Antioxidant signaling upon oxidative stress.

Background: Congenital hereditary endothelial dystrophy (CHED) is a rare genetic disease of the corneal endothelium with a very early onset of bilateral corneal edema due to degeneration and dysfunction of the corneal endothelium. Currently SLC4A11 is the only established causative gene for CHED, but not all these reported CHED patients could be explained by SLC4A11 deficiency, indicating that the genetic predisposition of CHED still requires further exploration.

Methods: Trio-based whole-exome sequencing was performed on a CHED patient and his unaffected parents.

Calcitriol Alleviates Hyperosmotic Stress-Induced Corneal Epithelial Cell Damage via Inhibiting the NLRP3-ASC-Caspase-1-GSDMD Pyroptosis Pathway in Dry Eye Disease.

Purpose: Inflammasome activation in response to elevated tear osmolarity behaves as an initial signal in dry eye-related corneal inflammation. Pyroptosis is another prominent consequence of inflammasome activation, which is featured by gasdermin D (GSDMD)-driven cell lysis. This study aims to explore the role of pyroptosis in dry eye, and also to verify if calcitriol, a potential therapeutic agent for dry eye, has certain effects against hyperosmotic stress (HS)-induced pyroptosis in human corneal epithelial cells (iHCECs) and the underlying mechanism.

Evaluating the association between single nucleotide polymorphisms in the stonin 2 () gene and keratoconus in a Han Chinese population.

Background: A recent genome-wide association study (GWAS) identified a significant association between the single nucleotide polymorphism (SNP) rs2371597 in the stonin 2 gene () and keratoconus (KCTN) susceptibility. The current study further explored the association between and KCTN susceptibility in an independent Han Chinese population.

Methods: Three SNPs (rs2371597, rs8004137, and rs8008602) located in the gene were examined in 164 Han Chinese patients with KCTN and 239 age- and gender-matched healthy subjects.

Novel Mutations in That Associated With Peters' Anomaly Caused Abnormal Intracellular Protein Retention and Decreased Cellular Resistance to Oxidative Stress.

Peters' anomaly (PA) is a rare form of anterior segment dysgenesis characterized by central corneal opacity accompanied by iridocorneal or lenticulo-corneal adhesions. Although genetic mutations, particularly those affecting transcription factors that function in eye development, are known to cause PA, the etiology of this disease remains poorly understood. In this study, 23 patients with PA were recruited for panel sequencing.

Calcitriol inhibits apoptosis via activation of autophagy in hyperosmotic stress stimulated corneal epithelial cells in vivo and in vitro.

Background: Previously, calcitriol has been demonstrated as a potential therapeutic agent for dry eye, whilst its role on corneal epithelium death remains unclear. This study aims to investigate the relationship between apoptosis and autophagy on dry eye related scenario, as well as the effect of calcitriol and its potential mechanism.

Methods: In vitro, immortalized human corneal epithelial cells (iHCEC) were cultured in hyperosmotic medium with or without various concentrations of calcitriol and other reagents.

Replication of the Association Between Keratoconus and Polymorphisms in and in a Han Chinese Population.

Keratoconus (KC) is a complex ocular disease that is affected by both genetic and non-genetic triggers. A recent genome-wide association study (GWAS) identified a genome-wide significant locus for KC in the region of (rs61876744), as well as a suggestive signal in the (rs10831500) locus. In order to validate their findings, here we performed a replication study of the Han Chinese population, with 120 sporadic KC cases and 206 gender and age matched control subjects, utilizing the TaqMan SNP genotyping assays.

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells.

Background: In herpes simplex epithelial keratitis, excessive TLR3-induced cellular responses after virus infection evoke inflammatory cascades that might be destructive to the host cornea. Nerve growth factor (NGF), a pluripotent neurotrophic factor with immune regulatory effect, was proved to be effective in Herpes simplex keratitis (HSK) treatment, although the detailed mechanisms remain unclear. This study aims to investigate the effects of NGF on modulating inflammatory responses triggered by TLR3 activation in human corneal epithelial cells (HCECs) in vitro.

Shared gene signature between pterygium and meibomian gland dysfunction uncovered through gene-expression meta-analysis.

Background: Pterygium and meibomian gland dysfunction (MGD) are two clinically correlated ocular diseases. We propose to investigate the shared gene signature between pterygium and MGD.

Methods: Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database.

MiR-21 promotes pterygium cell proliferation through the PTEN/AKT pathway.

Purpose: To evaluate the effect of the overexpression of miR-21 on the properties of pterygium and examine whether miR-21 promotes the proliferation of pterygium cells through targeting the PTEN/AKT signaling pathway.

Methods: Information regarding patient gender, age, and pterygium severity was gathered. Expression of miR-21 was obtained through examination of excised pterygium tissues and superior conjunctiva tissues with real-time PCR.

A comprehensive evaluation of 181 reported variants in patients with macular corneal dystrophy.

Macular corneal dystrophy (MCD) is an autosomal recessive disease featured by bilateral progressive stromal clouding and loss of vision, consequently necessitating corneal transplantation. Variants in gene have been recognized as the most critical genetic components in MCD. Although many variants have been described until now, the detailed mechanisms underlying MCD are still far from understood.

Calcitriol inhibits ROS-NLRP3-IL-1β signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells.

Purpose: The activation of ROS-NLRP3-IL-1β signaling axis induced by hyperosmotic stress (HS) has been recognized as a key priming stage of epithelial inflammation in dry eye pathogenesis. The current study aims to investigate whether calcitriol, the active metabolite of vitamin D, could protect cells against HS-induced inflammation through modulating this critical step.

Methods: Human corneal epithelial cells (iHCECs) were cultured in hyperosmotic medium (450 mOsM) with various concentrations of calcitriol.