Ocular Surface Development and Gene Expression

Swamynathan, Sudha

doi:10.1155/2013/103947

Cited by 52 publications

(65 citation statements)

References 228 publications

(286 reference statements)

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“…The ocular surface epithelia, including the stratified but nonkeratinized corneal, limbal, and conjunctival epithelium, in concert with the epidermal, keratinized eyelid epithelium, function together to enable eye health and vision (Swamynathan, 2013). The transparent cornea is essential for vision, and increases in cellular stratification and keratinization of the cornea result in vision loss or blindness and are associated with many severe ocular surface diseases (Li et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…The transparent cornea is essential for vision, and increases in cellular stratification and keratinization of the cornea result in vision loss or blindness and are associated with many severe ocular surface diseases (Li et al, 2007). The limbus exists at the transition between corneal and conjunctival epithelium, and is a stem cell niche containing limbal stem cells that migrate centripetally to maintain the cornea (Pellegrini et al, 1999;Swamynathan, 2013). Conjunctival epithelium, which encompasses the palpebral conjunctiva, the fornix and the bulbar conjunctiva, lines the inner surface of the eyelid, is composed of stratified epithelium interspersed with goblet cells, and adjoins the cornea at the limbus (Wei et al, 1993(Wei et al, , 1997Pellegrini et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium

et al. 2014

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The ocular surface epithelia, including the stratified but nonkeratinized corneal, limbal and conjunctival epithelium, in concert with the epidermal keratinized eyelid epithelium, function together to maintain eye health and vision. Abnormalities in cellular proliferation or differentiation in any of these surface epithelia are central in the pathogenesis of many ocular surface disorders. Goblet cells are important secretory cell components of various epithelia, including the conjunctiva; however, mechanisms that regulate goblet cell differentiation in the conjunctiva are not well understood. Herein, we report that conditional deletion of transforming growth factor β receptor II (Tgfbr2) in keratin 14-positive stratified epithelia causes ocular surface epithelial hyperplasia and conjunctival goblet cell expansion that invaginates into the subconjunctival stroma in the mouse eye. We found that, in the absence of an external phenotype, the ocular surface epithelium develops properly, but young mice displayed conjunctival goblet cell expansion, demonstrating that TGFβ signaling is required for normal restriction of goblet cells within the conjunctiva. We observed increased expression of SAM-pointed domain containing ETS transcription factor (SPDEF) in stratified conjunctival epithelial cells in Tgfbr2 cKO mice, suggesting that TGFβ restricted goblet cell differentiation directly by repressing Spdef transcription. Gain of function of Spdef in keratin 14-positive epithelia resulted in the ectopic formation of goblet cells in the eyelid and peripheral cornea in adult mice. We found that Smad3 bound two distinct sites on the Spdef promoter and that treatment of keratin 14-positive cells with TGFβ inhibited SPDEF activation, thereby identifying a novel mechanistic role for TGFβ in regulating goblet cell differentiation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium

et al. 2014

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“…Excessive secretion of mucins by goblet cells can change the viscosity of mucus, leading to inefficient mucociliary clearance and pulmonary obstruction in respiratory diseases [1,7,38,41] ( Table 1). The conjunctiva lines the inner surface of the eyelid and is continuous with the eyelid epithelium and the corneal epithelium via the limbus [46] (Figure 1). In contrast to gastrointestinal and pulmonary epithelia, conjunctival epithelium is composed of only two cell types: the keratinocyte and the goblet cell [47].…”

mentioning

confidence: 99%

“…In the intestine, KLF4 is restricted to differentiated, post-mitotic cells, including goblet cells, and induces cell cycle arrest [46,[67][68][69][70], whereas KLF5 is expressed in basal cells within the crypts and promotes cellular proliferation [67,71,72]. Notch signaling has been shown to inhibit KLF4, providing one possible mechanism for restriction of KLF4 expression and goblet cell differentiation in the crypts [65,66].…”

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confidence: 99%

Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia

McCauley

Guasch

2015

Trends in Molecular Medicine

180

132

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Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense system. In this review we summarize what is known about the signaling pathways that control goblet cell differentiation in the intestine, the lung, and the ocular surface, and we discuss a novel functional role for goblet cells in mucosal epithelial immunology. We highlight the cell type-specificity of the circuitry regulating goblet cell differentiation and shed light on how changes to these pathways lead to altered goblet cell function, a prominent feature of mucosa-associated diseases.

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“…Most AS structures are derived from the neural crest cells (NCC), including the corneal stroma and endothelium, ciliary body muscle and body, iris stroma, and the trabecular meshwork [5]. In mice, migrating NCC of the periocular mesenchyme (POM) begin to invade the AS of the eye between E11.5 and E12.5, and differentiate into corneal endothelial cells and keratocytes [6,7]. By E16.5, the presumptive iris is visible and detaches from the cornea, while the drainage structures (trabecular meshwork and Schlemm's canal) continue to develop postnatally [8].…”

Section: Introductionmentioning

confidence: 99%

Primary cilia deficiency in neural crest cells causes Anterior Segment Dysgenesis

Portal

Lwigale

Rompolas

et al. 2019

Preprint

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During eye embryogenesis, neural crest cells (NCC) of the periocular mesenchyme (POM) migrate to the anterior segment (AS) of the eye and then differentiate into the corneal stroma and endothelium, ciliary body, iris stroma, and the trabecular meshwork. Defective development of these structures leads to anterior segment dysgenesis (ASD) that in 50% of the cases leads to glaucoma, a leading cause of blindness. Here, we show that the primary cilium is indispensable for normal AS development and that its ablation in NCC induces ASD phenotypes including; small and thin cornea, impaired stromal keratocyte organization, abnormal iridocorneal angle with reduced anterior chamber and corneal neovascularization. These defects are similar to those described in patients with AS conditions such as Axenfeld-Rieger syndrome and Peter's anomaly. Mechanistically, disruption of the primary cilium in the NCC resulted in reduced hedgehog (Hh) signaling in the POM, canonically activated by the Indian Hedgehog ligand expressed by endothelial cells of the choroid. This caused decreased cell proliferation in a subpopulation of POM cells surrounding the retinal pigmented epithelium.Moreover, primary cilium ablation in NCC also led to a decreased expression of Foxc1 and Pitx2, two transcription factors identified as major ASD causative genes. These findings suggest that primary cilia are indispensable for NCC to form normal AS structures via Hh signaling.Defects in primary cilia could, therefore, contribute to the pathogenesis of ASD, and to their complications such as congenital glaucoma.

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Ocular Surface Development and Gene Expression

Cited by 52 publications

References 228 publications

TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium

TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium

Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia

Primary cilia deficiency in neural crest cells causes Anterior Segment Dysgenesis

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