| Depression of intraocular pressure following inactivation of connexin43 in the nonpigmented epithelium of the ciliary body. | |
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MedLine Citation:
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PMID: 19168903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Conditional inactivation of connexin43 (Cx43) in the pigmented epithelium of the mouse eye results in a reduction in aqueous humor production and complete loss of the vitreous chamber. It was proposed that gap junctions between pigmented and nonpigmented epithelia of the ciliary body are critical for the production of the aqueous humor. To form such junctions, Cx43 in the pigmented epithelium must interact with connexin(s) present in the adjacent cells of the nonpigmented epithelium. The importance of Cx43 expression in the nonpigmented epithelium for the establishment of gap junctions and the regulation of intraocular pressure was tested. METHODS: To inactivate Cx43 in the nonpigmented epithelium of the mouse eye, a mouse line was crossed with a floxed Cx43 locus (Cx43(flox/flox)) and a transgenic mouse line expressing cre recombinase under the control of the Pax6alpha promoter. General eye structure was evaluated by light microscopy, gap junctions were analyzed by electron microscopy, and intraocular pressure was directly assessed with micropipettes. RESULTS: In Pax6alpha-cre/Cx43(flox/flox) mice, Cx43 was partially inactivated in the nonpigmented epithelium of the ciliary body and iris. Animals developed dilatations between the pigmented and nonpigmented epithelia and displayed a significant reduction in intraocular pressure. However, gap junctions between the ciliary epithelial layers were decreased but not eliminated. CONCLUSIONS: Cx43 expression in the nonpigmented epithelium of the ciliary body contributes to the formation of gap junctions with the cells of the pigmented epithelium. These gap junctions play a critical role in maintaining the physical integrity of the ciliary body epithelium. Although the partial loss of Cx43 from the nonpigmented epithelium was correlated with a measurable drop in intraocular pressure, possible changes in Cx43 in the aqueous outflow pathway may provide an additional contribution to the observed phenotype. |
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Authors:
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Mónica R Calera; Zhao Wang; Roberto Sanchez-Olea; David L Paul; Mortimer M Civan; Daniel A Goodenough |
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1764013 - Unequal narrowing of the visual field in a +gz environment. 18172103 - Effects of cyclic intraocular pressure on conventional outflow facility. 6969603 - The prevalence of glaucoma. |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-01-24 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 50 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-23 Completed Date: 2009-05-12 Revised Date: 2011-01-14 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 2185-93 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02125, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ciliary Body / metabolism*, ultrastructure Connexin 43 / physiology* Epithelium / metabolism* Eye Proteins / physiology Gap Junctions / physiology* Histocytochemistry Homeodomain Proteins / physiology In Situ Hybridization Integrases / metabolism Intraocular Pressure / physiology* Mice Mice, Knockout Mice, Transgenic Paired Box Transcription Factors / physiology Polymerase Chain Reaction Repressor Proteins / physiology beta-Galactosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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EY02430/EY/NEI NIH HHS; EY13624/EY/NEI NIH HHS; EY14127/EY/NEI NIH HHS; GM37751/GM/NIGMS NIH HHS; R01 EY002430-32/EY/NEI NIH HHS; R01 EY002430-33/EY/NEI NIH HHS; R01 GM037751-23/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Connexin 43; 0/Eye Proteins; 0/Homeodomain Proteins; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Repressor Proteins; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases; EC 3.2.1.23/beta-Galactosidase |
| Comments/Corrections | |
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