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Chinda Hemmavanh, Edgar Espana, David Birk; Collagen XII regulates collagen fibril packing, lamellar organization, stromal architecture and corneal function. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5256.
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© ARVO (1962-2015); The Authors (2016-present)
Collagen XII is a fibril associated collagen (FACIT) that has been hypothesized to regulate stromal organization and extracellular matrix interactions. Regulated fibril assembly, packing, and organization into orthogonal lamellae are vital for corneal function. The purpose of this study is to elucidate the role(s) of collagen XII in the regulation of fibril assembly and organization as well as stromal structure which is required for corneal function.
The role of collagen XII in the cornea was studied using wild type and Col12a1-/- mice. Collagen XII expression patterns were analyzed using immuno-chemical, biochemical and molecular approaches. Lamellae and fibril organization were analyzed using transmission electron microscopy in P30 corneas (n=3). Corneal thickness was measured at P30 and P60 using optical coherence tomography (n=6).
Collagen XII was homogeneously localized throughout the corneal stroma in postnatal and mature corneas (P4-P90). Expression from P4-P30 was relatively constant during this period with a slight decrease in collagen XII expression at P90. Stromal organization was disrupted in the absence of collagen XII. Lamellar organization was disrupted in the Col12a1-/- compared to wild type corneas. Individual lamellae were disorganized with an increased density of fibrils in the Col12a1-/- corneas compared to controls. Mature Col12a1-/- corneas were significantly thicker than the wild type controls. At P30, the Col12a1-/- corneal thickness was 132.2 ± 9.2μm (mean ± sd) compared to 101.4 ± 3.8μm for the wild type corneas. The P60 thickness values were 117.4 ± 9.5μm and 93.8 ± 4.9μm for Col12a1-/- and wild type corneas respectively.
Collagen XII is present in the corneal stroma during critical stages of postnatal development. The disruption of lamellar structure and organization in Col12a1-/- corneas supports an important regulatory role for collagen XII in higher order extracellular matrix assembly, i.e., the organization of fibrils into well ordered orthogonal lamellae. The data also support a role for collagen XII in fibril packing with decreased interfibrillar spacing observed in the collagen XII-null corneas. In addition, the data indicate that the regulation of lamellar assembly has a role in determination of corneal thickness. Ultimately collagen XII regulates lamellar organization, stromal integrity, and corneal function.
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