Identification of genes associated with lens regeneration from the cornea in Xenopus laevis tadpoles
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ABSTRACT:
ORGANISM(S): Xenopus laevis
PROVIDER: GSE28014 | GEO | 2011/09/14
SECONDARY ACCESSION(S): PRJNA137989
REPOSITORIES: GEO
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Project description:Surgical removal of the lens from larval Xenopus laevis results in a rapid transdifferention of central corneal cells to form a new lens. The trigger for this process is understood to be an induction event arising from the unprecedented contact between the cornea and the vitreous humour that occurs following lens removal. The identity of this trigger is unknown. Here, we have used a functional transgenic approach to show that BMP signalling is required for lens regeneration and a microarray approach to identify genes that are upregulated specifically during this process. Analysis of the array data strongly implicates Wnt signalling and Pitx transcription factors in this process. Pluripotency genes, in contrast, are not upregulated, supporting the idea that corneal cells transdifferentiate without returning to a stem cell state. Furthermore, several genes from the array were expressed in the forming lens during embryogenesis. One of these, nipsnap1, is a known direct target of BMP signalling. We suggest that, as with tail regeneration, activation of multiple developmental signalling pathways could drive lens regeneration from the cornea. Three biological replicates of each of three sample types were analysed. For each replicate, lens tissue (L) was derived from 5 lenses dissected from stage 50 tadpoles. Similarly, 7-8 corneas dissected from stage 50 tadpoles from which the lens had been removed 3 days previously were pooled for each biologocal replicate (R). These samples should contain tissue that is changing from cornea to lens, to regenerate the missing lens. Finally, 7-8 corneas from eyes of tadpoles at the same stage that had the cornea lifetd but the lens left in place 3 days earlier were pooled for each biological replicate (sham operated corneas, designated S).
2011-09-13 | E-GEOD-28014 | biostudies-arrayexpress
Project description:The cornea continues to mature after birth to develop a fully functional, refractive and protective barrier tissue. Here we investigated the complex biological events underlying this process by profiling global genome-wide gene expression patterns of the immature postnatal day 10 and seven week-old adult mouse cornea. The lens and tendon were included in the study to increase the specificity of genes identified as up regulated in the corneal samples. Notable similarities in gene expression between the cornea and the tendon were in the mesenchymal extracellular matrix collagen (types I, III, V, VI) and proteoglycan (lumican, decorin and biglycan) genes. Expression similarities in the cornea and lens were limited to certain epithelial genes and the crystallins. Approximately 76 genes were over expressed in the cornea samples that showed basal expression levels in the lens and tendon. Thirty-two of these were novel with no known functions in the cornea. These include genes with a potential role in protection against oxidative stress (Dhcr24, Cdo1, Akr1b7, Prdx6), inflammation (Ltb4dh, Wdr1), ion-transport (Pdzk1ip1, Slc12a2, Slc25a17) and transcription (Zfp36l3, Pdzk1ip1). Direct comparison of the cornea of two ages showed selective up regulation of 50 and 12 genes in the P10 and adult cornea, respectively. Of the up regulated P10 genes several encode extracellular matrix collagens and proteoglycans that are stable components of the adult cornea and their high transcriptional activity at P10 indicate a period of active corneal growth and matrix deposition in the young cornea. Much less is known about the genes selectively over expressed in the adult cornea; some relate to immune response and innervations (Npy), and possibly to electron transport (Cyp24a1, Cyp2f2) and others of yet unknown functions in the cornea (Rgs10, Psmb8, Xlr4)). This study detected expression of genes with known functions in the cornea, providing additional validation of the microarray experiments. Importantly, it identified several novel genes whose functions have not been investigated in the cornea.
2008-07-23 | GSE11900 | GEO
Project description:The cornea continues to mature after birth to develop a fully functional, refractive and protective barrier tissue. Here we investigated the complex biological events underlying this process by profiling global genome-wide gene expression patterns of the immature postnatal day 10 and seven week-old adult mouse cornea. The lens and tendon were included in the study to increase the specificity of genes identified as up regulated in the corneal samples. Notable similarities in gene expression between the cornea and the tendon were in the mesenchymal extracellular matrix collagen (types I, III, V, VI) and proteoglycan (lumican, decorin and biglycan) genes. Expression similarities in the cornea and lens were limited to certain epithelial genes and the crystallins. Approximately 76 genes were over expressed in the cornea samples that showed basal expression levels in the lens and tendon. Thirty-two of these were novel with no known functions in the cornea. These include genes with a potential role in protection against oxidative stress (Dhcr24, Cdo1, Akr1b7, Prdx6), inflammation (Ltb4dh, Wdr1), ion-transport (Pdzk1ip1, Slc12a2, Slc25a17) and transcription (Zfp36l3, Pdzk1ip1). Direct comparison of the cornea of two ages showed selective up regulation of 50 and 12 genes in the P10 and adult cornea, respectively. Of the up regulated P10 genes several encode extracellular matrix collagens and proteoglycans that are stable components of the adult cornea and their high transcriptional activity at P10 indicate a period of active corneal growth and matrix deposition in the young cornea. Much less is known about the genes selectively over expressed in the adult cornea; some relate to immune response and innervations (Npy), and possibly to electron transport (Cyp24a1, Cyp2f2) and others of yet unknown functions in the cornea (Rgs10, Psmb8, Xlr4)). This study detected expression of genes with known functions in the cornea, providing additional validation of the microarray experiments. Importantly, it identified several novel genes whose functions have not been investigated in the cornea. Experiment Overall Design: Briefly, the corneas were dissected free of the limbus from postnatal day 10 (P10) and seven-week old (adult) mice. To enrich for stromal contribution, the epithelium was scraped off and the cornea placed in TRIzol (Invitrogen Life Technologies, Carlsbad, CA). The scraping off of the epithelium reduced, but did not abrogate epithelial contribution, as judged by the expression of known epithelial markers. The lens and the flexor digitorum longus (FDL) tendon were removed from seven-week old adult mice for isolation of total RNA. For the adult cornea three independent preparations of total RNA was generated. For all the other tissues two independent preparations of total RNA were used. The adult and the P10 microarrays were used as baselines in our previous study of corneal cells in culture to identify genes differentially expressed by cultured cells of the stroma (Chakravarti et al. 2004). Experiment Overall Design: The output fluorescence of the scanned images was analyzed first using the Affymetrix Microarray Suite 5.0 software to compute absolute expression, background calculation and detection call (present, absent or marginal). Background signal was between 42 to 55 arbitrary units, while the noise to signal ratio was between 1.42 to 1.78 arbitrary units. The expression data from all nine arrays were further analyzed as follows. The model-based DNA-Chip Analyzer (dChip) software (http://www.dchip.org/) was used to normalize the data from the image files for array-to-array comparison (Li and Wong 2001). This software uses an invariant-set algorithm as a basis for normalization and a model-based expression index to calculate the expression value for each transcript. To identify gene expression patterns that were statistically significantly different between any two given tissue types, we used the following criteria: (1) fold change ⥠2; (2) difference of mean expression index ⥠100 arbitrary units; (3) t-statistic, p < 0.05.
2008-10-21 | E-GEOD-11900 | biostudies-arrayexpress
Project description:Characteristic structural details of the cornea are transparency, the absence of blood vessels, and the presence of numerous sensory nerve endings. The corneal epithelium is one of the most densely innervated tissues of the body. The characteristics of the cornea are established during fetal development, and are lost in adult life when the cornea regenerates after injury. The common reaction of the cornea to injury is the formation of opaque scars, the ingrowth of blood vessels, and distinct changes in the innervation pattern. Scar formation of the cornea is critically modulated by the expression of transforming growth factor-beta (TGF-beta). To identify genes that are important for corneal transparency, dense innervation and absence of blood vessels by comparing corneas from wildtype mice with those that are under the influence of high doses of TGF-beta. Transparency, dense innervation, and absence of blood vessels in the cornea all depend on the expression of a critical set of genes that are not expressed when TGF-beta is present. Mice were generated that overexpress TGF-beta under control of a strong lens-specific promoter. These mice developed opaque corneas that are vascularized and lack sensory nerves. In addition, these corneas were densely populated with cells expressing neural cell adhesion protein. RNA was isolated from corneas of transgenic animals and wildtype littermates in order to analyze differentially expressed genes and to identify those that are only expressed in transparent, avascular, and densely innervated wildtype corneas.
2008-06-15 | E-GEOD-6676 | biostudies-arrayexpress
Project description:Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing.
2022-02-05 | GSE191228 | GEO
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:Characteristic structural details of the cornea are transparency, the absence of blood vessels, and the presence of numerous sensory nerve endings. The corneal epithelium is one of the most densely innervated tissues of the body. The characteristics of the cornea are established during fetal development, and are lost in adult life when the cornea regenerates after injury. The common reaction of the cornea to injury is the formation of opaque scars, the ingrowth of blood vessels, and distinct changes in the innervation pattern. Scar formation of the cornea is critically modulated by the expression of transforming growth factor-beta (TGF-beta). To identify genes that are important for corneal transparency, dense innervation and absence of blood vessels by comparing corneas from wildtype mice with those that are under the influence of high doses of TGF-beta. Transparency, dense innervation, and absence of blood vessels in the cornea all depend on the expression of a critical set of genes that are not expressed when TGF-beta is present. Mice were generated that overexpress TGF-beta under control of a strong lens-specific promoter. These mice developed opaque corneas that are vascularized and lack sensory nerves. In addition, these corneas were densely populated with cells expressing neural cell adhesion protein. RNA was isolated from corneas of transgenic animals and wildtype littermates in order to analyze differentially expressed genes and to identify those that are only expressed in transparent, avascular, and densely innervated wildtype corneas. Keywords: TGF-beta overexpression
2007-01-09 | GSE6676 | GEO
Project description:TGFBIp-related corneal dystrophy (CD) is the most common form of stromal corneal dystrophy. Although CD is a group of inheritable and progressive corneal diseases, non-inheritable cases of corneal amyloid deposition are reported. TGFBIp-CD is characterized by the accumulation of insoluble protein deposits consisting smaller proteolytic fragments of TGFBIp in the corneal tissues, eventually leading to progressive corneal opacity. Maximum density of these aggregates is in the corneal center implicating the local absence of amyloid controlling factors. Currently, no other treatment options are available besides the surgical replacement of the affected corneal tissues with a donor’s cornea. Here we show that neuroprotective ATP-independent amyloid β chaperone L-PGDS abundant in cerebrospinal fluid but absent in the corneal tissues can effectively disaggregate amyloids in vitro and in the surgically excised human cornea of patients with TGFBIp-CD.
2023-05-10 | PXD038281 | Pride
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
Project description:his study present the protein profile of diseased cornea from granular corneal dystrophy patients developing protein accumulation after LASIK surgery. Extracted ion chromatography (XIC) label free quantification was perform using Mascot Distiller software. In addition, 2D-PAGE followed by western blot against the mutated protein TGFBIp that cause the protein accumulation in the cornea, was examined and compared to normal corneal tissue.
2016-02-19 | PXD001997 | Pride