anatomy and physiology of cornea

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Sanket ParajuliCORNEA

Embryology

Dev. of the cornea is triggered by the separation of the lens vesicle from the surface ectoderm

Epithelium : surface ectoderm 40days

Stroma (7 weeks) and bowmans membrane (4 month): mesenchyme

Endothelium (40days) : neural crest cells

Descemets membrane(4th month) : endothelium

CORNEA

Transparent avascular tissue with a smooth, convex surface and concave inner surface

Forms the principal refractive surface, accounting for 70% (40-45 diopters) of the total refractive power

Most of the refraction of the eye occurs not in the lens but at the front surface of the cornea at the tear/air interface

Refractive index of cornea = 1.37

The curvature of the cornea is greater than that of the sclera so that a slight external furrow (scleral sulcus) separates it from the sclera. This furrow may be demonstrated in the living eye by specular reflection from the overlying tear film.

Its structure fulfills the functional demands ie it must be transparent, refract light, contain the IOP and provide a protective interface with the environment

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DIMENSIONS

Anteriorly::: elliptical ..11.7 mm wide &10.6 mm high

Posterior surface :: circular..11.7 mm in diameter

This difference is due to the greater overlap of sclera and conjunctiva above and below than laterally

The cornea forms part of what is almost a sphere, but it is usually more curved in the vertical than the horizontal meridian, giving rise to astigmatism 'with the rule'.

At birth the cornea is slightly thicker than that in children, perhaps reflecting the onset of endothelial function close to the time of birth. Its surface area is about 1.3 cm2, one-sixth of the surface area of the globe (Table 7.1).

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The axial thickness of the cornea is 0.52 mm with a peripheral thickness of 0.67 mm

Central 1/3rd of cornea = optical zone

Radius of curvature of the anterior surface is about 7.8 mm and that of the posterior 6.5 mm, in adult males.

Peripheral cornea is more flattened

TOPOGRAPHY

Corneal shape is important to the fitting of contact lenses

Average anterior radius of curvature 7.2- 8.4

The cornea is flatter in men than in women

The anterior curvature of the cornea is spherical over a small zone 2-4 mm in diameter which is decentered upwards and outwards relative to the visual axis, but correctly centered for the pupillary aperture (which lies 0.4 mm temporally). This is sometimes termed the corneal apex or cap (Fig)

The apical radius of the posterior corneal surface is 5.8 mm; the radius flattens in the periphery, faster than the anterior radius.. The cornea flattens slightly on convergence

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The corneal curvature varies from apex to limbus. There is greater flattening nasally than temporally, and above than below, although variations occur

These features influence the fitting of contact lenses

The cornea flattens slightly on convergence

The apical radius of the posterior corneal surface is 5.8 mm; the radius flattens in the periphery, faster than the anterior radius.

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STRUCTUREBehind the precorneal film are five tissue layers :1. Epithelium2. Bowman's layer3. Stroma4. Descemet's membrane5. Endothelium

Researchers revealed a new layer of tissue in the human cornea. NamedDuas layer, after Professor Harminder Dua from the University of Nottingham in the U.KBetween the corneal stroma and the Descemets membrane

Epitheliumstratified, squamous and non-keratinized It is continuous with that of the conjunctiva at the corneal limbus, but differs strikingly in possessing no goblet cells. The epithelium consists of 5-6 layers of nucleated cells Basal cells: stand in a palisade like manner in perfect alignment on a basal lamina & form the germinative layer of the epithelium, continuous peripherally with that of the limbus. These basal cells are columnar with nucleus oriented parallel to the cell's long axis.

b) The second epithelial layer (the 'wing' or 'umbrella' cells) consists of polyhedral cells, convex anteriorly, which cap the basal cells, and send processes between them. The long axes of their oval nuclei are parallel to corneal surface

c) The next two or three layers are also polyhedral and become wider and increasingly flattened towards the surface. (surface cells)The surface cells have the largest surface area and this is greater in the periphery compared to centrally

Ultrastructural features

Mitochondria: scarce --basal cells but abundant --wing and middle cell layers

High glycogen content in the form of granules, especially in the wing and superficial cells

Amount of glycogen falls in hypoxic conditions, or during wound healing

The basal cells are connected to one another by desmosomes and to basal lamina by hemidesmosomes

In basal cells , anchoring filaments pass through the hemidesmosomal structures to be inserted into the underlying basal lamina.

This is a strong attachment and if the corneal surface is scraped by a scalpel blade, fragments of the ruptured basal cells remain attached to the basal lamina

Between contiguous epithelial cells, in addition to the desmosomal connections, tight junctions (zonulae occludentes) run circumferentially between contiguous surface cells

These tight junctions are relatively impermeable to small molecules such as sodium ions and makes the epithelium semipermeable

The most superficial cells of the epithelium exhibit surface microvilli or microplicae

Microvilli serve a physical function in stabilizing the deep precorneal tear film

Scanning microscopy also demonstrates 'light' and 'dark' cells with varying density and type of microvilli present It has been suggested that the dark cells are older and about to desquamate

Langerhans cells have been identified in the corneal epithelium( in the peripheral region)

These cells and OR positive macrophages are almost totally absent from the central cornea but will populate this region in response to infection.

Basal lamina

Basal lamina is secreted by the basal cells, which also synthesize the hemidesmosomal structures concerned in attachment of epithelium to the lamina The lamina consists of collagen and glycoprotein constituents integrated structurally with the underlying Bowman's layer, to which it is firmly attached by an array of short anchoring filaments

Derma epidermal junction of cornea/conjunctiva is similar as of skin

Structures present in basal lamina:a) lamina lucida b) lamina densa c) anchoring fibrils & anchoring plaques :electron-dense fibrils form narrow bundles which insert into the subjacent stroma or Bowman's laver

6 Integrin is localized along the lateral and basal membranes of the basal cells but is found in combination with 4 within the hemidesmosome. With age the distribution of 6 becomes less continuous, but the density of hemidesmosomes does not change .

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These structures are composed of type VII collagen(lamina densa contains type IV collagen)

The cohesion between the basal lamina and Bowman's zone loosened by lipid solvents, stromal oedema and inflammation but it remains attached to the basal cells

The basal lamina may be destroyed by proteolytic enzymes such as trypsin and chymotrypsin

With old age, and in diabetes, it becomes thickened and multilamellar

Metabolism

The corneal epithelium is rich in glycogen, which serves as an energy store in the aerobic conditions .. (With the eyes open, the tear PaO2 is 155 mmHg; With the eyes closed this drops to about 55 mmHg)

In hypoxic conditions, such as those induced by a tight contact lens, the epithelial glycogen level falls.

Hypoxia also produces a profound fall in corneal sensitivity

The concentrations of acetylcholine and acetylcholinesterase in the corneal epithelium are as high as in brain tissue

A role for acetylcholine in transport processes has been postulated or in regulating epithelial cell mitosis, because acetylcholine may stimulate cyclic GMP (cGMP) production, and cGMP stimulates epithelial cell mitosis

Turnover

studies using titrated thymidine suggested that the epithelium was replaced approximately weekly by the division of basal epithelial cells

One daughter cell from a division remained in the basal layer while the other was displaced to the surface, from where it was ultimately shed

Germinative region of the corneal epithelium(stem cells), lies at the limbus.

Cells migrate from the limbus towards the centre of the cornea

limbal basal cells can be distinguished from corneal epithelial cells and from other limbal epithelial cells by their expression of cytokeratins

corneal epithelial cells and suprabasal limbal epithelial cells express cytokeratins typical of differentiated cells (e.g. CK3)

Basal limbal cells are negative for these cytokeratins and positive for a group of acidic cytokeratins staining with the antibody AEl

on the basis of experimental evidence, that there was both a limbal basal and a corneal basal epithelial source for corneal epithelial cells (XYZ hypothesis)

The sequence of events from proliferation of stem cells to desquamation of superficial corneal epithelial cells is thought to involve cell division by the slow cycling stem cells

Attachment The basal epithelial cells are firmly attached to basal lamina by hemidesmosomes and anchoring filaments

Bowman's layer (anterior limiting lamina)