Universität zu Köln

Sun, Mei, Zafrullah, Nabeel, Devaux, Floriane, Hemmavanh, Chinda, Adams, Sheila, Ziebarth, Noel M., Koch, Manuel, Birk, David E. and Espana, Edgar M. (2020). Collagen XII Is a Regulator of Corneal Stroma Structure and Function. Invest. Ophthalmol. Vis. Sci., 61 (5). ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. The aim of this study was to determine the roles of collagen XII in the regulation of stromal hierarchical organization, keratocyte organization, and corneal mechanics. METHODS. The temporal and spatial expression of collagen XII at postnatal days 4, 10, 30, 90, and 150 were evaluated in wild-type (WT) mice. The role of collagen XII in hierarchical organization was analyzed by measuring fibril diameter and density, as well as stromal lamellar structure, within ultrastructural micrographs obtained fromWT and collagen XIIdeficient mice (Col12a1(-/-)). Keratocyte morphology and networks were assessed using actin staining with phalloidin and in vivo confocal microscopy. The effects of collagen XII on corneal biomechanics were evaluated with atomic force microscopy. RESULTS. Collagen XII was localized homogeneously in the stroma from postnatal day 4 to day 150, and protein accumulation was shown to increase during this period using semiquantitative immunoblots. Higher fibril density (P < 0.001) and disruption of lamellar organization were found in the collagen XII null mice stroma when compared to WT mice. Keratocyte networks and organization were altered in the absence of collagen XII, as demonstrated using fluorescent microscopy after phalloidin staining and in vivo confocal microscopy. Corneal stiffness was increased in the absence of collagen XII. Young's modulus was 16.2 +/- 5.6 kPa in WT and 32.8 +/- 6.4 kPa in Col12a1(-/-) corneas. The difference between these two groups was significant (P < 0.001, t-test). CONCLUSIONS. Collagen XII plays a major role in establishing and maintaining stromal structure and function. In the absence of collagen XII, the corneal stroma showed significant abnormalities, including decreased interfibrillar space, disrupted lamellar organization, abnormal keratocyte organization, and increased corneal stiffness.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sun, Mei UNSPECIFIED UNSPECIFIED UNSPECIFIED Zafrullah, Nabeel UNSPECIFIED UNSPECIFIED UNSPECIFIED Devaux, Floriane UNSPECIFIED UNSPECIFIED UNSPECIFIED Hemmavanh, Chinda UNSPECIFIED UNSPECIFIED UNSPECIFIED Adams, Sheila UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziebarth, Noel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Birk, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Espana, Edgar M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-334871
DOI:	10.1167/iovs.61.5.61
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	61
Number:	5
Date:	2020
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTRACELLULAR-MATRIX; MESSENGER-RNA; FIBRILLOGENESIS; FORM; EXPRESSION; MUTATIONS; INTEGRITY; VARIANTS; DECORIN; PROTEIN Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33487