Abstract
In the cornea, the precise organisation of fibrillar collagen and associated proteoglycans comprising the stromal extracellular matrix plays a major role in governing tissue form and function. Recently, abnormal collagen alignment was noted in the misshapen corneas of mature chickens affected by the retinopathy, globe enlarged (rge) mutation. Here we further characterize corneal ultrastructural changes as the rge eye develops post-hatch. Wide-angle X-ray scattering disclosed alteration to dominant collagen lamellae directions in the rge chick cornea, compared to age-matched controls. These changes accompanied eye globe enlargement and corneal flattening in affected birds, manifesting as a progressive loss of circumferential collagen alignment in the peripheral cornea and limbus in birds older than 1 month. Collagen intermolecular separation was unchanged in rge. However, small-angle X-ray scattering results suggest collagen fibril separation and diameter increase more rapidly towards the corneal periphery in rge at 3 months post-hatch compared to controls, although central collagen fibril diameter was unchanged. By transmission electron microscopy utilising cuprolinic blue stain, the morphology and distribution of stromal proteoglycans were unaltered in rge corneas otherwise demonstrating abnormal collagen fibril organisation. From a numerical simulation of tissue mechanics, progressive remodelling of stromal collagen in rge during globe enlargement post-hatch appears to be related to the corneal morphometric changes presented by the disease.
Highlights
Animal vision diseases in which normal eye growth is compromised can provide useful opportunities for determining the factors that govern the size and shape of ocular components
The bulk of mechanical loading on the cornea is borne by type I fibrillar collagen in the stroma, arranged in a layered structure that is unique amongst connective tissues (Maurice, 1957; Komai and Ushiki, 1991)
The results presented confirm alterations to peripheral collagen fibril orientation post-hatch
Summary
Animal vision diseases in which normal eye growth is compromised can provide useful opportunities for determining the factors that govern the size and shape of ocular components. Rge is characterized clinically by progressive retinal degeneration and total visual loss by $1 month post-hatch (Inglehearn et al, 2003; Montiani-Ferreira et al, 2003, 2005). The rge phenotype is defined by eye globe enlargement and associated thickening and flattening of the cornea occurring secondary to retinal dysfunction (Montiani-Ferreira et al, 2003; Inglehearn et al, 2003) (Fig. 1). A significant increase in radial globe diameter is apparent approximately 1 month post-hatch, with axial eye q Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, April 2008.
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