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Cell regulation of collagen fibril macrostructure during corneal morphogenesis

Koudouna, Elena ORCID:, Mikula, Eric, Brown, Donald J., Young, Robert D. ORCID:, Quantock, Andrew J. ORCID: and Jester, James V. 2018. Cell regulation of collagen fibril macrostructure during corneal morphogenesis. Acta Biomaterialia 79 , pp. 96-112. 10.1016/j.actbio.2018.08.017

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While tissue form and function is highly dependent upon tissue-specific collagen composition and organization, little is known of the mechanisms controlling the bundling of collagen fibrils into fibers and larger structural designs that lead to the formation of bones, tendons and other tissues. Using the cornea as a model system, our previous 3 dimensional mapping of collagen fiber organization has demonstrated that macrostructural organization of collagen fibers involving interweaving, branching and anastomosing plays a critical role in controlling mechanical stiffness, corneal shape and refractive power. In this work, the cellular and mechanical mechanisms regulating critical events in the assembly of collagen macrostructure are analysed in the developing chicken cornea. We elucidated the temporal events leading to adult corneal structure and determined the effects of intraocular pressure (IOP) on the organization of the collagen macrostructure. Our findings indicate that the complex adult collagen organization begins to appear on embryonic day 10 (E10) after deposition of the primary stroma and full invasion of keratocytes. Importantly, organizational changes in keratocytes appearing at E9 preceded and predicted later changes in collagen organization. Corneal collagen organization remained unaffected when the development of IOP was blocked at E4. These findings support a primary role for keratocytes in controlling stromal organization, mechanical stiffness and corneal shape that are not regulated by the IOP. Our findings also suggest that the avian cornea represents an excellent experimental model for elucidating key regulatory steps and mechanisms controlling the collagen fiber organization that is critical to determining tissue form and function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Elsevier
ISSN: 1742-7061
Funders: BBSRC BB/M025349/1 (AJQ), NIH NEI EY024600 (JVJ), Research to Prevent Blindness, Inc. The Skirball Program in Molecular Ophthalmology
Date of First Compliant Deposit: 29 August 2018
Date of Acceptance: 17 August 2018
Last Modified: 08 Jan 2024 16:35

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