Corneal endothelium

The corneal endothelium is a monolayer of specialized, flattened, mitochondria-rich cells that lines the posterior surface of the cornea and faces the anterior chamber of the eye. The corneal endothelium governs fluid and solute transport across the posterior surface of the cornea and actively maintains the cornea in the slightly dehydrated state that is required for optical transparency.

Embryology and anatomy
The corneal endothelium is embryologically derived from the neural crest. The postnatal total endothelial cellularity of the cornea (approximately 300,000 cells per cornea) is achieved as early as the second trimester of gestation. Thereafter the endothelial cell density (but not the absolute number of cells) rapidly declines in direct proportion to the areal growth of the fetal cornea, achieving a final adult density of approximately 2400 - 3200 cells/mm². The normal corneal endothelium is a hexagonal monolayer of uniformly sized cells. This honeycomb tiling scheme yields the greatest efficiency, in terms of total perimeter, of packing the posterior corneal surface with cells of a given area.

Physiology
The principal physiological function of the corneal endothelium is to allow leakage of solutes and nutrients from the aqueous humor to the more superficial layers of the cornea while at the same time actively pumping water in the opposite direction, from the stroma to the aqueous. This dual function of the corneal endothelium is described by the "pump-leak hypothesis." Since the cornea is avascular, which renders it optimally transparent, the nutrition of the corneal epithelium, stromal keratocytes, and corneal endothelium must occur via diffusion of glucose and other solutes from the aqueous humor, across the corneal endothelium. The corneal endothelium then actively transports water from the stromal-facing surface to the aqueous-facing surface by an interrelated series of active and passive ion exchangers. Critical to this energy-driven process is the role of Na+/K+ATPase and carbonic anhydrase. Bicarbonate ions formed by the action of carbonic anhydrase are translocated across the cell membrane, allowing water to passively follow.

Mechanisms of corneal edema
Corneal endothelial cells are post-mitotic and divide rarely, if at all, in the post-natal human cornea. Wounding of the corneal endothelium, as from trauma or other insults, prompts healing of the endothelial monolayer by sliding and enlargement of adjacent endothelial cells, rather than mitosis. Endothelial cell loss, if sufficiently severe, can cause endothelial cell density to fall below the threshold level needed to maintain corneal deturgescence. This threshold endothelial cell density varies considerably amongst individuals, but is typically in the range of 500 - 1000 cells/mm². Corneal edema can also occur as the result of compromised endothelial function due to intraocular inflammation or other causes. Excess hydration of the corneal stroma disrupts the normally uniform periodic spacing of Type I collagen fibrils, creating light scatter. In addition, excessive corneal hydration can result in edema of the corneal epithelial layer, which creates irregularity at the optically critical tear film-air interface. Both stromal light scatter and surface epithelial irregularity contribute to degraded optical performance of the cornea and can compromise visual acuity.

Causes of endothelial disease
Damage or disease of the corneal endothelium is the predominant indication for corneal transplantation. Leading causes of endothelial failure include inadvertent endothelial trauma from intraocular surgery (such as cataract surgery) and Fuchs' dystrophy. Surgical causes of endothelial failure include both acute intraoperative trauma as well as chronic postoperative trauma, such as from a malpositioned intraocular lens or retained nuclear fragment in the anterior chamber. Other risk factors include narrow-angle glaucoma, aging, and iritis.

Treatment for endothelial disease
There are no medical treatments that can promote wound healing or regeneration of the corneal endothelium. The only available treatment for irreversible corneal endothelial failure is surgical corneal transplantation. This can include penetrating keratoplasty, a conventional technique in which full-thickness replacement of the cornea is performed, or posterior lamellar keratoplasty (also known as endokeratoplasty), a more recently developed technique in which only the posterior aspect of the cornea is removed and replaced.