Cell-free fat extract promotes cornea epithelial repair and restores neurodegeneration via an anti-inflammation pathway
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE287673 | GEO | 2025/10/28
REPOSITORIES: GEO
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Project description:Cell-free fat extract promotes cornea epithelial repair and restores neurodegeneration via an anti-inflammation pathway
| PRJNA1214233 | ENA
Project description:The cornea is the transparent tissue at the forefront of the eye. Its outermost layer, the corneal epithelium, acts as a protective barrier for the ocular chamber. The cornea is avascular and its homeostasis relies on alternative sources to receive nutrients and growth factors, essential for maintaining its physiological functions and transparency. These sources include the corneal epithelium itself, the innervation and the tear film, collectively forming the corneal microenvironment. Any disruption to this finely balanced system (due to injury, ageing or diseases) can impair corneal transparency and lead to a progressive opacification, ultimately resulting in vision loss. Corneal blindness affects over 28 million people worldwide and represents the fourth leading cause of blindness. Among corneal injuries, abrasions are defined by a transient disruption in the integrity and cohesion of the epithelial barrier and are the most common type of eye injury encountered in clinical practice. Abrasion triggers a complex corneal wound healing process, involving the whole microenvironment, essential to restore transparency. However, a delayed or defective healing can lead to severe complications and visual impairments. Frequently caused by traumatic events, abrasion is also a mandatory step for some refractive surgeries such as photorefractive keratectomy (PRK). Understanding the molecular mechanisms underlying corneal wound healing is thus critical to improve the clinical outcomes and minimize the risk of complications such as haze or delayed epithelial regeneration. The aim of this study is to characterize the temporal dynamics of the tear fluid proteome following PRK and identify molecular signatures associated with corneal epithelial healing. We conducted a prospective cohort study involving longitudinal proteomic analysis of tear samples with mass spectrometry at baseline (preoperative), 30 minutes postoperatively (day 0), and on day 3 after PRK. Ten healthy adult patients undergoing bilateral PRK for myopia correction were included in this study. Corneal epithelial injury was induced by bilateral PRK, a standardized surgical model of epithelial removal followed by laser ablation.
2025-11-10 | PXD067691 | Pride
Project description:The cornea is the transparent tissue covering the anterior part of the eye. Its main roles are to convey the light toward the retina, and to act as a protective barrier against infection or injury for the eye. The transparency of the cornea is a crucial component of its functionality and is the result of specific architecture and cell arrangements. The inner layer of the cornea is the endothelium, composed of a monolayer of endothelial cells. The next layer is the stroma, representing about two third of the thickness of the cornea, and is mainly composed of a specifically arranged extracellular matrix, secreted by few keratocytes1–4. Finally, the external layer is a life-long renewed pluristratified epithelium. The regulated epithelial homeostasis, crucial to maintain the corneal transparency, relies on stem and progenitor cells5. To coordinate epithelial homeostasis and healing, and to adequately respond to any change in the corneal environment, this tissue is highly innervated6,7. The corneal innervation is mainly composed of A and C sensory fibres whose cell bodies are located in the ophthalmic branch of the trigeminal ganglion8. Those fibres penetrate the corneal stroma from the periphery, as bundles of fibres branching and spreading within the stroma9. When entering in the epithelium, the fibres branche again and radiate horizontally to form the subbasal plexus. Finally, the sensory fibres shift orientation to reach the top of the epithelium, where they end up as free nerve endings6,7. There are three classes of fibres innervating the cornea: the mechano-nociceptors, the cold sensing neurons and the polymodal nociceptors, reacting respectively to mechanical, thermal and chemical stimuli10,11. Stimuli transduction is not the only role of the corneal innervation, as these fibres have a crucial role on epithelial homeostasis through the secretion of trophic factors essential for epithelial cell survival12. Due to its localization, the cornea is highly exposed to ultraviolet radiation and high oxygen tension, making it particularly vulnerable to mitochondrial defects13. These defects can be either inherited or non-inherited. Inherited forms result from mutations in mitochondrial DNA (mtDNA) or nuclear gene defects affecting mitochondrial function14. Inherited mitochondrial dysfunction is a key factor in the progression of Fuchs endothelial corneal dystrophy (FECD) and keratoconus13,15,16. Non-inherited mitochondrial dysfunction, on the other hand, can occur due to spontaneous mtDNA mutations or somatic mutations that accumulate with age, rendering the mitochondrial metabolism less efficient with time17. To date, the impact of inherited mitochondrial dysfunctions on corneal epithelium physiology has not been extensively studied. Case reports have linked mitochondrial diseases to corneal cloudiness18,19, perforation20 and edema21. Furthermore, mitochondrial defect was associated to inflammatory context and ROS production in ocular surface pathologies13,22. Despite these studies, the direct effect of mitochondrial disfunction on corneal biology remains elusive. Among the known pathologies originating from an inherited mitochondrial dysfunction, the dominant optic atrophy (DOA) is an inherited blinding disease caused by the degenescence of the retinal cell ganglions forming the optic nerve23. The mutation of the gene OPA1 is responsible for the majority of the DOA diagnostics. OPA1 gene encodes for a mitochondrial protein involved in the fusion process and is essential to maintain the organelle integrity. Generally, optic neuropathy is the characteristic syndrome for DOA, but a subset of patients, called dominant optic atrophy plus (DOA+), also declare extra-ocular syndromes such as ataxia, deafness and peripheral neuropathies24,25. A mouse model, bearing the OPA1delTTAG mutation, recapitulates the degenerative syndromes encountered in DOA+ patients25.. While DOA is associated with lens cloudiness, no report has linked DOA to ocular surface defects. Here, we investigated the impact of OPA1 delTTAG mutation on mouse cornea as its structure includes a large amout of sensory fibres that are crucial to maintain corneal homeostasis.
2024-07-25 | PXD052337 | Pride
Project description:The cornea is the transparent tissue on the anterior surface of the eye. It is notably composed of a squamous stratified epithelium that forms a barrier protecting the ocular chamber. As the cornea is avascular, the delivery of nutrients and growth factors, required for corneal physiology, is essential. These nutrients and factors come from 1) the epithelium itself, 2) the innervation, and 3) the tear film, which together form the corneal microenvironment. Disturbances of this microenvironment, in the context of injury, aging or corneal pathology, can lead to progressive corneal opacification, resulting in blindness. More than 28 million people suffer from mono- or bilateral corneal blindness, making it the fourth cause of blindness worldwide. Corneal abrasion is the most common eye injury encountered in clinics, but poorly studied, making it a major issue in ophthalmology. It is characterized by a transient rupture in the integrity and cellular cohesion of the epithelial barrier, which are brought back thanks to a corneal wound healing process. The aim of this study is therefore to highlight the molecular impact of corneal abrasion on the microenvironment, and more specifically on the tear film. We performed a longitudinal study to identify a specific proteome of tears before and after corneal abrasion in mice. The corneal abrasion was performed unilaterally on female mice. Tear fluid samples were collected from the wounded eye and the contralateral eye before corneal abrasion and during the wound healing process up to 24hrs post-abrasion.
2025-11-10 | PXD061492 | Pride
Project description:To study the development and composition of human ocular surface, we performed single cell (sc) RNA-Seq at key embryonic, fetal and adult stages and generated the first atlas of the corneal and conjunctival cell types from development to adulthood. The conjunctival epithelium is the first to be specified in the epithelial layer , followed by the corneal epithelium and the establishment of proliferative epithelial progenitors, which predate the formation of limbal niche by a few weeks. Bioinformatic comparison of adult cell clusters identified GPHA2,a novel cell-surface marker for quiescent limbal stem cells (qLSCs), whose function is to maintain qLSCs self-renewal. Combining scRNA- and ATAC-Seq analysis, we identified multiple upstream regulators for qLSCs and transit amplifying (TA) cells and demonstrated a close interaction between the immune cells and epithelial stem and progenitor cells in the cornea. Single cell RNA-Seq analysis indicated loss of qLSCs and acquisition of proliferative limbal epithelial progenitor markers during limbal epithelial cell expansion: this phenomenon was independent of culture method used. Extending the single cell analyses to Keratoconus, we were able to reveal activation of collagenase in the corneal stroma and a reduced pool of TA cells in the corneal epithelium as two key mechanistic changes underlying the disease phenotype. Our scRNA-Seq data comparisons of developing and adult cornea and conjunctiva provide a unique resource for defining pathways/genes that could lead to improvement in ex vivo expansion methods for cell based replacement therapies and better understanding and treatment of ocular surface disorders.
2021-04-19 | GSE155683 | GEO
Project description:Recently we had discovered a solid cord like structure at the limbus of human eyes, termed as the Limbal Epithelial Crypt (LEC). It arises from the undersurface of the interpalisade rete ridges and extends towards the conjunctiva over the conjunctival stroma. Anatomical and immunohistochemical studies have shown it to be potentially a Stem Cell Niche. To confirm this hypothesis we conducted comparative gene expression profile of LEC with pathway and Geneontology studies in comparison with other ocular surface epithelial regions such as cornea, limbus, LEC stroma and conjunctiva. Frozen tissue blocks of corneoscleral buttons dissected from cadaver eyes were cryosectioned. These tissue sections from different ocular surface regions were laser microdissected. Extracted RNA was amplified & hybridized to 30,000k Human spotted cDNA microarray chips. Raw data obtained with Genepix Pro6 software was filtered, normalized & analysed on BASE & Jexpresspro software. Unpaired T-Test, Significance Analysis of Microarrays were performed on the data. Database for Annotation, Visualisation, and Integrated Discovery (DAVID) (http://www.DAVID.niaid.nih.gov) and Ingenuity Pathway Analysis (IPA) was used to determine the enriched GO terms and pathways in the differentially expressed genes. Quantitative gene expression analysis (qPCR) and immunohistochemistry was performed on the genes of interest. Statistical analysis for real time PCR was performed on SPSS16 to determine the normalised expression of gene of interest on ocular surface regions. Samples were prepared from five human ocular surface epithelial regions such as Cornea, Limbus, LEC, LEC Stroma, Conjunctiva. There were four replicates in each groups except Cornea and Conjunctiva with 3 each. The Standard Probe (SP) was prepared from mixing equal amount of Corneal and conjunctival epithelial RNA followed by ethanol precipitation. Samples were labelled with Cy5 dye and Standard Probe with Cy3 Dye. These were mixed in equal amount to prepare hybrid probes which were then hybridised to microarray slide.
2010-03-23 | E-GEOD-19035 | biostudies-arrayexpress
Project description:Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein lacripep reverses the pathological outcomes of dry eye through restoring the extensive network of corneal nerves that are essential for tear secretion, barrier function, epithelial homeostasis and wound healing. Intriguingly, the restorative effects of lacripep occur despite extensive immune cell infiltration, suggesting tissue reinnervation and regeneration can be achieved under chronic inflammatory conditions. In summary, our data highlight lacripep as a first-in-class regenerative therapy for returning the cornea to a near homeostatic state in individuals who suffer from dry eye.
2022-07-18 | GSE208297 | GEO
Project description:The cornea, composed of epithelium, stroma and endothelium, protects the anterior compartment of the eye from damage and allows transmission of light into the eye. While well described morphologically, no studies have investigated the global gene expression changes in the cornea throughout the mouseM-bM-^@M-^Ys life. We characterized the global gene expression profile of mouse cornea from early development through aging, and compared to gene expression in other epithelial tissue, to identify cornea enriched genes, pathways, and transcriptional regulators. We identified Ehf, an ets family transcription factor, as being highly selectively expressed in the corneal epithelium compared to the stroma, and highly expressed in cornea compared to other epithelial tissues. siRNA experiments and Ehf ChIP-Seq on mouse corneal epithelium confirm the role of this factor in promoting epithelial identity and cell differentiation, and suggest it carries out these functions through interactions with other cornea epithelial differentiation factors including Klf4. Whole eye globes were dissected from wild type CB6 mice. Corneal epithelium was isolated by digestion in 50% EMEM/dispase II with 50 mM sorbitol for two hours at 37M-BM-0C. ChIP was performed with an Ehf antibody, and was sequenced with an input control.
2013-08-27 | E-GEOD-44741 | biostudies-arrayexpress
Project description:The rapid and effective regeneration of corneal epithelial cells depends on limbal stem cells (LSCs). The LSCs of mouse can be subdivided into quiescent LSCs (located on the outer limbus, qLSCs) and active LSCs (located on the inner limbus, aLSCs). Here, we used single-cell RNA sequencing to decipher the transcriptional changes in qLSCs and aLSCs and their niche regulations during the corneal wound healing, and reconstructed the pseudotime trajectory and differentiation of LSCs. Our comparative study identified a transcription factor Creb5, expressed in LSCs, that was significantly upregulated after corneal epithelial injury, and the loss-of-function experiments revealed that silencing Creb5 delayed the corneal epithelial healing. Besides, we predicted a significant increase in the number of ligand-receptor pairs for intercellular communications during corneal epithelial wound healing, especially between immune cells and LSCs, implying the participation of various niche cells in limbal stem cell kinetics during corneal epithelial regeneration. Overall, our research reveals numerous findings on the behavior and functionality of LSCs during corneal wound healing, providing reference for the discovery of mechanisms and potential clinical interventions of ocular surface reconstruction.
2024-07-10 | GSE247392 | GEO
Project description:Mitochondrial dysfunctions are detrimental to organ metabolism. The cornea, transparent outmost layer of the eye, is prone to environmental aggressions, such as UV light, and therefore dependent on adequate mitochondrial function. While several reports have linked corneal defects to mitochondrial dysfunction, the impact of OPA1 mutation, known to induce such dysfunction, has never been studied in this context. We used the mouse line carrying OPA1delTTAG mutation to investigate its impact on corneal biology. To our surprise, neither the tear film composition nor the corneal epithelial transcriptomic signature were altered upon OPA1 mutation. However, when analyzing the corneal innervation, we discovered an undersensitivity of the cornea upon the mutation, but an increased innervation volume at 3 months. Furthermore, the fibre identity changed with a decrease of the SP+ axons. Finally, we demonstrated that the innervation regeneration was less efficient and less functional in OPA1+/- corneas. Altogether, our study describes the resilience of the corneal epithelial biology, reflecting the mitohormesis induced by the OPA1 mutation, and the adaptation of the corneal innervation to maintain its functionality despite its morphogenesis defects. These findings will participate to a better understanding of the mitochondrial dysfunction on peripheral innervation.
2024-08-21 | GSE266324 | GEO