Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma

Abstract

The optical and biomechanical properties of the cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from limbus-to-limbus. In the peripheral cornea/limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy.We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease.

The hierarchical response of human corneal collagen to load

“…It is possible that such a mechanism prevents changes in intraocular pressure from significantly affecting focus. The recent discovery of an elastic sheet-like network in the periphery [31] , [54] has strengthened suggestions that the peripheral cornea acts as a strain absorber, deforming under changes in intraocular pressure and thereby minimising changes in curvature in the paracentral and central cornea [29] , which could be detrimental to vision. Such a system would function best if the deformation was as efficient as possible, and a synergy between networks of near-lossless elastic fibres and collagen fibrils that can deform longitudinally via a subfibrillar mechanism may be the optimal arrangement.…”

Involvement of anterior and posterior corneal surface area imbalance in the pathological change of keratoconus

“…However, it still remains unclear as to whether changes in the anterior surface 9 , posterior surface 5 , 10 , or both surfaces of the cornea 11 are the first to arise in the early stage of KC. In keratoconic eyes, the organization of the collagen lamellae is disrupted, and the distribution of microfibril bundles is very different, thus resulting in a loss of tensile strength and the progression of ectasia 13 , 32 . Our findings, which demonstrated the smaller As/Ps ratio in keratoconic eyes via 3D analysis, suggest that a protrusion of the posterior cornea occurs prior to changes being observed on the anterior corneal surface, thus leading to enlargement of the posterior corneal surface area compared to the anterior surface area and the formation of early-stage KC.…”

Protective Effects Oncorneal Endothelium During Intracameral Irrigation Using N-(2)-l-alanyl-l-Glutamine

“…Sample preparation for TEM were performed according to method described previously (White et al, 2017). Briefly, the corneas were harvested and fixed immediately in 0.1M phosphate buffer containing 2.5% glutaraldehyde at 4°C and washed three times in PBS before post-fixing in 1% osmium tetroxide.…”