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Keratoconus: Histology

Histology of Keratoconus

The histology of the cornea (from the Greek "histos", tissue) is the microscopic study of corneal tissue. In the absence of an animal model (Keratoconus appears to be a purely human condition), the histological study of Keratoconus is largely based on obtaining corneas (removed) for the production of a corneal graft. Histological changes caused by keratoconus affect all tissue layers of the cornea, but are not specific and distributed preferentially in the center of the cornea. The epithelial layer is often thinned in the center of the cornea (see below), and there are localized ruptures or irregularities in the basal membrane. The lack of specificity of these elements, that a chronic regular trauma such as friction could alone cause, invalidate a priori the presence of a dystrophy.


Layer of Bowman

The Bowman layer is the most superficial part of the stroma. It is located under the epithelial layer, its thickness is limited to about ten microns. The Bowman layer presents irregularities or even localized ruptures during the evolution of the keratoconus (recall that these observations concern the advanced stages of the disease, since they are performed on pimples of horns prélévés during of graft operation). There is sometimes a direct contact of the corneal stroma and the epithelial layer ("disappearance" of the Bowman layer). This layer being the most superficial area of the corneal stroma, it is particularly exposed to the trauma of the repeated eye rubbing.

Stroma and Collagen lamellae

At the level of the stromal layer there is a decrease in the number of collagen lamellae and a spatial disorganization, without reducing the thickness of the lamellae itself. A decrease in the substance located along the collagen fibrils (Proteoglycans) has been reported. The density of kératocytaires cells decreases in particular in the anterior stroma in relation to the Bowman membrane as well as in the posterior 2/3 of the stroma. The composition of corneal collagen appears to be little altered during the evolution of Keratoconus (Zimmerman et al. Comparative stydues of Collagens in normal and keratoconus corneas. Exp Eye Res, 1988; 46 (3): 431-42).

The corneal nerves have an increase in diameter with some keratocytes associated with their outskirts.

It is interesting to note that this histological aspect is quite compatible with what would produce sustained mechanical stress such as that caused by the repeated eye rubbing. In addition, it concerns only part of the cornea tissue, located in the central region. This focal distribution (the periphery is spared) points to an external "local" actuator.


Descemet Membrane

In the most advanced forms, with major thinning, the Descemet membrane (at the posterior side of the cornea) exhibits localized fracture lines and folds without any real difference in the composition of the different protein constituents compared to normal corneas. The endothelial cell layer exhibits anomalies of form and density that may be related to localized ruptures of the Descemet membrane. This type of impairment is always observed in patients who rub their eyes in a particularly vigorous and prolonged manner.

Enzymatic changes

The cells within the different layers of the corneal tissue secrete different enzymes that affect the rate of cell growth or death. These enzymatic changes are usually attributed to a dysfunction of the cells that regulate the maintenance and renewal of the contact cells. In the stroma of the corneas with Keratoconus, there is an increase in enzymes and mediators that degrade the tissue (collagenases, metalloproteinases). Apoptosis is the death of genetically programmed cells, and favored by some mediators. It has been shown that for normal eyes, 60 seconds of eye rubbing are sufficient to induce the local secretion of these molecules (MMP-13, TNF-alpha, interleukin-6) (Balasubramanian SA1, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus. Optom Exp Clin. 2013; 96 (2): 214-8.)

 Therefore, the eye rubbing, in addition to contributing to the spatial disorganization of the collagen lamellae, results in the expression of biological mediators that cause tissue loss and thinning of the cornea. During the keratoconus, this thinning is focal, and located in the central (and Paracentral) region of the cornea.


See also:

No rub, no Cone, the Keratoconus Conjecture

Rebuttal of classical theory: Marfan syndrome 

Keratoconus and corneal topography

Suspicious forms of Keratoconus

Keratoconus subclinical

Consulter des case documentés avec suivi de kératocône (en anglais)

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