Differential gene expression in anatomical compartments of the human eye

Diehn, J.J.; Diehn, Maximilian; Marmor, Michael F.; Brown, Patrick O.

doi:10.1186/gb-2005-6-9-r74

Cited by 51 publications

(16 citation statements)

References 68 publications

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“…To identify other potential retinal autoantigens that are aire-regulated in the thymus, we generated a list by compiling publicly available gene chip datasets that examine aire-deficient versus aire-sufficient mTEC gene expression ( 3 , 13 ) and gene chip datasets identifying retinal expressed genes ( Fig. 3 E ) ( 21 ). In an attempt to confirm that these genes were in fact aire regulated, we used real-time PCR to study the expression of four of these genes in thymic stroma from aire-sufficient and aire-deficient mTECs.…”

Section: Resultsmentioning

confidence: 99%

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

DeVoss¹,

Hou

Johannes³

et al. 2006

The Journal of Experimental Medicine

249

246

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The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals.

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Section: Resultsmentioning

confidence: 99%

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

DeVoss¹,

Hou

Johannes³

et al. 2006

The Journal of Experimental Medicine

249

246

View full text Add to dashboard Cite

show abstract

“…Many of the cornea genes are also expressed in the retina. Studies of the corneal transcriptome in other model species have frequently relied on subtractive approaches between cornea and other eye structures [ 48 ]. Our strategy to analyze cornea expression relative to the skin transcriptome thus reveals a different set of genes.…”

Section: Discussionmentioning

confidence: 99%

Molecular Description of Eye Defects in the Zebrafish Pax6b Mutant, sunrise, Reveals a Pax6b-Dependent Genetic Network in the Developing Anterior Chamber

et al. 2015

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The cornea is a central component of the camera eye of vertebrates and even slight corneal disturbances severely affect vision. The transcription factor PAX6 is required for normal eye development, namely the proper separation of the lens from the developing cornea and the formation of the iris and anterior chamber. Human PAX6 mutations are associated with severe ocular disorders such as aniridia, Peters anomaly and chronic limbal stem cell insufficiency. To develop the zebrafish as a model for corneal disease, we first performed transcriptome and in situ expression analysis to identify marker genes to characterise the cornea in normal and pathological conditions. We show that, at 7 days post fertilisation (dpf), the zebrafish cornea expresses the majority of marker genes (67/84 tested genes) found also expressed in the cornea of juvenile and adult stages. We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. Ultrastructure analysis revealed a disrupted corneal endothelium. pax6b mutants show loss of corneal epithelial gene expression including regulatory genes (sox3, tfap2a, foxc1a and pitx2). In contrast, several genes (pitx2, ctnnb2, dcn and fabp7a) were ectopically expressed in the malformed corneal endothelium. Lack of pax6b function leads to severe disturbance of the corneal gene regulatory programme.

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“…Previous studies have used microarray technology to investigate gene expression in normal human corneas (40,41). In these global studies, the entire cornea was used as the starting material, and no attempt was made to separate the epithelial compartment from the underlying stroma.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Profiling of Enriched Populations of Stem Cells Versus Transient Amplifying Cells

Zhou¹,

Lavker³

2006

Journal of Biological Chemistry

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The basal layer of limbal and central corneal epithelium is enriched in stem cells and transient amplifying cells, respectively. This physical separation of stem and transient amplifying cells makes the limbal/corneal epithelium an exceptionally suitable system for isolating basal cells enriched in these two proliferative populations. Prior attempts to isolate epithelial stem cells used methods such as proteolytic tissue dissociation and cell sorting that could potentially alter their gene expression profile. Using laser capture microdissection, we were able to isolate resting limbal and corneal basal cells from frozen sections with minimal tissue processing, thereby improving the yield and quality of RNA. Analyses of RNA isolated from 300 limbal and corneal basal cells from eight mice revealed a set of ϳ100 genes that are differentially expressed in limbal cells versus corneal epithelial basal cells. Semiquantitative reverse transcription-PCR confirmed the up-regulation of three limbal and three corneal genes. LacZ identification of epiregulin from epiregulin-null mice and immunohistochemical staining of wild type mice confirmed that epiregulin, one of the limbal epithelium-enriched genes, was associated with the limbal epithelial basal cells. Within the limbal and corneal basal cells, we detected previously unknown genes that were differentially expressed in these two regions that contribute further to our understanding of the unique heterogeneity of these two closely related basal cell populations. Our findings indicate that we can obtain accurate gene expression profiles of the stem cell-enriched limbal basal cell population in their "natural" quiescent state.The ability to identify, purify, and characterize epithelial stem cells is a critically important issue in epithelial stem cell biology as it will further our understanding on how stem cells are regulated. Of the various epithelial tissues studied, the limbal/corneal epithelium has yielded a great deal of information about stem cells (1). Based on a combination of (i) keratin expression data (2); (ii) in vivo and in vitro cell kinetic data (3-7); (iii) centripetal migration studies (8 -13); and (iv) corneal regeneration and reconstitution studies (14 -20), it is well accepted that the corneal epithelial stem cells are preferentially located in the limbal epithelial basal layer (for reviews, see Refs. 1 and 21-27). Furthermore, since the limbal stem cells can be millimeters away from their central corneal progeny transient amplifying (TA) 2 cells (1,2,4,7,24,28), the limbal/corneal system is ideally suited for isolating relatively pure populations of epithelial stem and TA cells for subsequent analyses.A lack of stem cell-specific markers has been an impediment for the isolation and subsequent biological and biochemical characterization of epithelial stem cells. Recently, transcriptional profiling of enriched populations of putative epithelial stem cells has been used to search for epithelial stem cellspecific markers. Methods used to isolate the putativ...

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Differential gene expression in anatomical compartments of the human eye

Cited by 51 publications

References 68 publications

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

Molecular Description of Eye Defects in the Zebrafish Pax6b Mutant, sunrise, Reveals a Pax6b-Dependent Genetic Network in the Developing Anterior Chamber

Transcriptional Profiling of Enriched Populations of Stem Cells Versus Transient Amplifying Cells

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