Primary cilia in corneal development and disease

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

As a transparent avascular tissue located at the front of the eyeball, the cornea is an important barrier to external damage. Both epithelial and endothelial cells of the cornea harbor primary cilia, which sense changes in the external environment and regulate intracellular signaling pathways. Accumulating evidence suggests that the primary cilium regulates corneal development in several ways, including participation in corneal epithelial stratification and maintenance of corneal endothelial cell morphology. In addition, the primary cilium has been implicated in the pathogenesis of several corneal diseases. In this review, we discuss recent findings that demonstrate the critical role of the primary cilium in corneal development. We also discuss the link between ciliary dysfunction and corneal diseases, which suggests that the primary cilium could be targeted to treat these diseases.

Related collections

Most cited references 68

Record: found
Abstract: found
Article: not found

Cellular signalling by primary cilia in development, organ function and disease

Zeinab Anvarian, Kirk Mykytyn, Saikat Mukhopadhyay … (2019)

Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis. The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium. The canonical hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis. Specific receptors and associated signal transduction proteins can also localize to primary cilia in a cell type-dependent manner; available evidence suggests that the ciliary constellation of these proteins can temporally change to allow the cell to adapt to specific developmental and homeostatic cues. Consistent with important roles for primary cilia in signalling, mutations that lead to their dysfunction underlie a pleiotropic group of diseases and syndromic disorders termed ciliopathies, which affect many different tissues and organs of the body. In this review we highlight central mechanisms by which primary cilia coordinate HH, G-protein-coupled receptor, WNT, receptor tyrosine kinase and TGFβ/BMP signalling, and illustrate how defects in the balanced output of ciliary signalling events are coupled to developmental disorders and disease progression.

0 comments Cited 280 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans.

Joan C. Marini, Antonella Forlino, Wayne Cabral … (2007)

Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proalpha1(I) and proalpha2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype-phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in alpha1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691-823 and 910-964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril-matrix interactions. Recurrences at the same site in alpha2(I) are generally concordant for outcome, unlike alpha1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In alpha2(I), lethal exon skipping events are located in the carboxyl half of the chain. Our data on genotype-phenotype relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events.

0 comments Cited 203 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Morphology of corneal nerves using confocal microscopy.

N Efron, P Soto (2001)

The aim of the current study was to evaluate the distribution and morphology of corneal nerves as seen by means of white light confocal microscopy. This study analyzed images of corneal nerves that were obtained using the Tomey Confoscan slit scanning confocal microscope (40x/0.75 objective lens). The images were classified according to their location within the cornea. The objective and subjective evaluation of the images involved measuring, grading, or judging a number of parameters from both individual pictures and from each single nerve fiber within any image. The in vivo observations made in this work are in agreement with those of previous histologic studies. The general scheme of corneal innervation is described as originating from thick and straight stromal nerve trunks that extend lateral and anteriorly and give rise to plexiform arrangements of progressively thinner nerve fibers at several levels within the stroma. From there, nerve fibers perforate Bowman's layer and eventually form a dense neural plexus just beneath the basal epithelial cell layer, which is characterized by tortuous and thin beaded nerve fibers interconnected by numerous nerve elements; nerve fibers from this plexus are known to be responsible for the innervation of the epithelium. This study provides convincing evidence of the suitability of confocal microscopy to image corneal nerves, the only drawback being the limited resolution in terms of the differentiation of the ultrastructure of nerve bundles.

0 comments Cited 88 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jun Zhou

Journal

Journal ID (nlm-ta): Zool Res

Journal ID (iso-abbrev): Zool Res

Journal ID (publisher-id): ZR

Title: Zoological Research

Publisher: Science Press (16 Donghuangchenggen Beijie, Beijing 100717, China )

ISSN (Print): 2095-8137

Publication date (Print): 18 September 2020

Volume: 41

Issue: 5

Pages: 495-502

Affiliations

[1 ] Institute of Biomedical Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China

[2 ] State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

Author notes

E-mail: junzhou@ 123456sdnu.edu.cn

Article

Publisher ID: zr-41-5-495

DOI: 10.24272/j.issn.2095-8137.2020.109

PMC ID: 7475007

PubMed ID: 32808517

SO-VID: 938cfe33-d4ae-4c2c-8101-302e0cef1a25

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 6 May 2020

Date accepted : 31 July 2020

Funding

This work was supported by the Taishan Scholars Program of Shandong Province (20161201)

Primary cilia in corneal development and disease

Read this article at

Abstract

Related collections

Sex hormones and lung development

Most cited references 68

Cellular signalling by primary cilia in development, organ function and disease

Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans.

Morphology of corneal nerves using confocal microscopy.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Funding

Categories

Comments

Comment on this article

Similar content 1,142

Cited by 8

Most referenced authors 876