Corneal physiology

OPTO : Ihsan Hmaid

CorneaCornea characteristics:

1. Forms the anterior 1/6 of the outer tunic .2. Completely transparent.3. Avascular.4. Ellipsoid and its vertical diameter is

11.5mm,and Its horizontal diameter is 12mm.

5. It is more thick in periphery 0.67mm than in center 0.52mm

6. It has smooth anterior and posterior surfaces .

7. Its radius of curvature is 7.8 mm in anterior surface but 7mm in posterior surface.

Functions of the cornea

1-It is considered the main refractive surface of the eye.

Its power about 42 diopters.

2-Protection of the intraocular structures of the eyes.

3-Passage of images of objects to the retina.

Factors affecting the corneal function

A - Transparency .

B - Regularity of curvature of its surface.

C - Smoothness of corneal surfaces.

The optical properties of the human cornea

Two major developments were made because current measurement techniques need improvement First, the VU topographer, which uses a color coded pattern, was validated with real eye data showing better performance compare to commercial ring topographers particularly in reconstructing the non-rotation symmetric features of the anterior corneal surface .

For example, ring topographers underestimate astigmatism of the anterior corneal surface by 4%. This underestimation increases with complexity of the surface. The astigmatism underestimation was found to be 13% for a post radially-keratotomized cornea. Second, the aberration contribution of the posterior surface was revealed using Scheimpflug photography. Results show that the contribution of the posterior surface to corneal coma aberration is negligible .

On the other hand, on average the posterior surface decreases corneal astigmatism by 31%. Also the contribution of the posterior surface to the spherical aberration of the cornea increase with age reaching up to 15% at age 65. Thus, measurement of the posterior surface is necessary to specify corneal astigmatism and spherical aberration accurately. The methods introduced in this study are useful for applications in laser refractive surgery, contact lens fitting and studies on wave aberration of the eye because it reveals the optical properties of the cornea more accurately.

Corneal stroma

stromal hydration and its regulation

Stromal hydration quantifies the water component of the stroma. Its regularization depends on different factors which were detailed as; swelling pressure, corneal endothelial and epithelial metabolic pumps and barriers, tear film evaporation and intraocular pressure. Finally, the authors present different clinical procedures for evaluating stromal hydration, such as, the fluorophotometry and hypoxic-stress. This study shows the importance of stromal physiology and the consequences of all surgical or pathological modifications .

Corneal keratocytes (corneal fibroblasts) are specialized fibroblasts residing in the

stroma. This corneal layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular matrix components. Keratocytes play the major role in keeping it transparent, healing its wounds, and synthesizing its components. In the unperturbed cornea keratocytes stay dormant, coming into action after any kind of injury or inflammation .

Some keratocytes underlying the site of injury, even a light one, undergo apoptosis immediately after the injury. Any glitch in the precisely orchestrated process of healing may cloud the cornea, while excessive keratocyte apoptosis may be a part of the pathological process in the degenerative corneal disorders such as keratoconus, and these considerations prompt the ongoing research into the function of these cells.

Origin and functions

Keratocytes are developmentally derived from the cranial population of neural crest cells, from whence they migrate to settle in the mesenchyme. In some species the migration from neural crest comes in two waves, with the first giving birth to the corneal epithelium and the second invading the epithelium-secreted stromal anlage devoid of cells;

in other species both populations come from a single wave of migration. Once settled in the stroma, keratocytes start synthesizing collagen molecules of different types (I, V, VI) and keratan sulfate. By the moment of eye opening after birth the proliferation of keratocytes is all but finished and most of them are in the quiescent state .

By the end of eye development an interconnected keratocyte network is established in the cornea, with dendrites of neighbouring cells contacting each over. Quiescent keratocytes synthesize the so-called crystallins, known primarily for their role in the lens. Corneal crystallins, like the lens ones, are thought to help maintain the transparency and optimal refraction .

They are also part of corneal antioxidant defense. Crystallins expressed by human keratocytes are ALDH1A1, ALDH3A1, ALDH2 и TKT. Different sets of crystallins are typical to distinct species. Keratan sulfate produced by keratocytes is thought to help maintain optimal corneal hydration; genetic disruption of its synthesis leads to the macular corneal dystrophy .

Corneal TransparencyThe cornea is highly transparent tissue with less 1% of light being scattered within it. The cornea transparency is maintained by two essential factors the physical characteristics of the cornea and controlled hydration also there are other factors are important in corneal transparency.

Stromal structureThe stroma is consist on based of lattice theory which postulated the stroma consist from collagen fibrils with small diameter and equal in diameter and the proteoglycans occupy the space between the collagen and keep the collagen at constant distance from each other, the separation between collagen fibrils is lees than one –half on wavelength of light so that the scatter light will elimination by destructive interference in all direction of light except the one direction.

(the direction of incident light)

Controlled hydration

It is the second factors important in determined the corneal transparency.The corneal hydration is controlled by to layers corneal epithelium and endothelium, both of these layers possesses barrier function prosperity and metabolic function pumping.Not: hydration propriety of stromal is determined by proteoglycans which contributes fixed negative charge of stroma.

The physiological hydration of cornea is maintained almost 78% if the cornea allowed to _+ 5% swell of this value it is being to scatter significant quantities of light. The endothelium barrier to free passage of molecule from aqueous is formed focal tight junction between the adjacent endothelium cells, however in contrast to barrier of endothelium the endothelium is lower resistance to electronic ions and small molecules, this leaky is offset by metabolic pumping of ions out the stroma by endothelium which maintain to make the aqueous side negative to balanced the stroma pressure.

Also the epithelium contributes corneal hydration control; it is act as barrier effect on ions such as NA, CL however in contrast to barrier of endothelium is lower resistance to water diffusion. When the cornea swells by water the light scattered increase with ensued transparency loss due to disruption of regular collagen fibrils.

The other factors maintain corneal transparency:

1-Corneal an avascular.

2-Unmyelination of corneal nerve fibers.

3-Degeneration of epithelium.

integrity of this layer and all layers of cornea))

4-Higher difference between refractive index of cornea and air.

Corneal Metabolism

It is the series of chemical reaction that place in living tissue. Where the constant metabolic activity in cornea is necessary to maintain on transparency, temperature and

hydration of cornea 78%))The metabolic occur in epithelium and endothelium, the main substance for this metabolic is glucose, oxygen, amino acid and vitamin .

Due to an avascular of cornea promotes to alternative routes of metabolic supply there are three possibilities one from aqueous second from atmosphere via tear film third from perilimbal blood vessels.The oxygen is mainly derived from atmosphere via tear film, in under steady-state the assume tear are saturated with oxygen and therefore the tension of oxygen crosspending to atmosphere is 155 mm hg at sea level in the open eye and when eye closed the tension is about 55 mm hg in this state the oxygen supply from perilimbal blood vessels .

The consumption rates of oxygen for layers of the cornea are not equals is as follog 40, 39, 21 epithelium, stroma, endothelium respectively.The glucose is derived from aqueous; the cornea derives the energy from the oxidative breakdown of carbohydrates and the glucose is primary substrate for generation of adenosine triphosphate is catabolized by two metabolic pathways as follog.

-Glycilytic ( Embden Meyerhof pathway) followed by Krebs tricarboxylic or citric acid cycle.

. -(Hexose monophosphate (pentose phosphateThe first step in glucose is phosphorlyation into glucose-6-phosphate:

1 -Embden Meyerhof pathway:

This the major one which account for about 85%, in this stage the enzymes called dehydrogenises act as catalysts for each in this process, in this process the glucose molecule is split into two molecules of pyruvic acid, in third of four stages of glycolytic process liberated energy is used to form two molecules of ATP from ADP and inorganic phosphate. If occur under aerobic condition six additional molecules of ATP are formed become eight,

while under anaerobic condition two molecules are only produce, in this state the pyruvic acid is convert into lactic acid without any significant energy where the lactic acid is build up in stroma and sufficient process is created to allow to water to drawn into stroma faster than endothelium pumping so that can occur stromal edema, this because the little energy for process of pumping.

In aerobic condition of glycolytic doesn’t stop in stage of produce lactic acid but continues until the final products are carbon dioxide and water this called Krebs tricarboxylic acid cycle or citric acid during this cycle the carbon dioxide and hydrogen atoms are released the hydrogen atom at length become oxidative to form water and total oxidative process synthesize further 30 ATP molecules.

2 -Hexose monophosphate:

Although the glycolytic pathway is principle pathway for oxidative of glucose but there other available of these the hexose monophosphate shunt is the most important.

In this state or pathway the glucose-6-phosphate is directly oxidative into carbon dioxide and water with energy of 35 ATP molecules.

The effect of contact lenses on corneal metabolism

Contact lens presents barrier between the cornea and atmosphere therefore Contact lens deprivation of oxygen to enter into cornea and consequently reduction in aerobic glycolysis.

Normally this situation is avoided with hard corneal lenses because they move and produced tears circulation this permitting some degree of oxygen and carbon dioxide exchange between the cornea and atmosphere.

Soft contact lenses also move on the eye but the circulation of the tear under soft contact lens is less although they have the advantage of transmission o oxygen in amount varying with the nature and thickness of materials but with sclera lenses tear exchange is less. The cornea can tolerated levels as low as 11-19 mm hg.

Corneal sensitivity

The sensitivity of the corneal is probably unsurpassed by that of any part of the body. Its varies from a maximum apically to a minimum at the peripheral with considerable drop in sensitivity at limbus. Sensitivity of the cornea is reduce with age, The peak sensitivity found in young patient and this is 3 times that found in oldest patient.

Sensitivity also varies with iris color, in this the blue-eye color have a greater sensitivity than those with dark –brown color. Sensitivity is the same in both eye and sexes in the normal circumstance .

Corneal display a diurnal variation in sensitivity with about third greater sensitivity as the day progresses from morning to evening. Diabetic, Albinism, and all disease affecting the cone of the corneal causes reduction in sensitivity.

The corneal temperature

The central has a temperature of 34°C, which appears to increase towards the periphery and is found to be nearly 0.50°C warmer at the limbus. The cooling of the cornea follog a blink seems to be slower in those who exhibit a lower blink rate than normal .

The normal corneal temperature may alter during contact lens wear. Corneal temperature can be measured by a wide-field, colour-coded infra-red imaging device, and a thermography-visual-system.

Endothelium

Endothelium every 1mm2 has 2800 – 3200 endothelial cell. The whole number is about 500000 cells which has a hexagonal shape.

hexagonal shape

corneal endothelium

The corneal endothelium is a single layer of cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris.

It 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.

Hexagonal cells of corneal endothelium visualized by specular microscopy.

Physiology of corneal endothelium

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.

Vertical section of human cornea from near the margin.

(Corneal endothelium)

Endothelial physiology and intraocular lens implantation.

The endothelium is the cellular monolayer which lines the posterior surface of the cornea. This layer is important in clinical ophthalmology because it is vital to maintenance of the transparency of the cornea and vision through its pump and barrier functions which limit the ingress of fluid into the cornea from the aqueous .

When the function of the corneal endothelium becomes compromised, the corneal stroma swells as it hydrates. Subsequently, epithelial bullae form with painful recurring epithelial erosions, and finally corneal scarring and blindness result. The relatively vulnerable position of the corneal endothelium renders it susceptible to iatrogenic injury during intraocular procedures, especially IOL implantation: the poor regenerative (mitotic) capacity of the human corneal endothelium limits its ability to recover normal function once it is injured.

The functional reserve of corneal endothelium.

With recent advances in our knowledge of corneal physiology, coupled with the development and increasing availability of the specular microscope as a clinical instrument, valid observations relating the morphologic appearance of the corneal endothelium to its functional capacity are within our reach .

Manual methods of data analysis are cumbersome, time consuming, and associated with human error and investigator bias. The Omnicon pattern analysis system lends itself to objective analysis of morphologic features, offers the possibility of quantifying the data obtained and, hopefully, will lead to a better understanding of the many aspects of endothelial cell morphology which, in total, relate to the functional reserve of a given cornea .

Epithelium

Embryologically, the corneal epithelium is derived from surface ectoderm at approximately 5–6 weeks of gestation. It is composed of nonkeratinized, nonsecretory, stratified squamous epithelium, which is 4–6 cell layers thick (40–50 μm). The epithelium is covered with a tear film of 7 μm thickness, which is optically important in smoothing out microirregularities of the anterior epithelial surface .

Corneal epithelium

Without this film, degradation of visual images results. The tear−air interface, together with the underlying cornea, provides roughly two thirds of the total refractive power of the eye. The mucinous portion of tears, which forms the undercoat of the tear film and is produced by the conjunctival goblet cells, interacts closely with the corneal epithelial cell glycocalyx to allow hydrophilic spreading of the tear film with each eyelid blink .

Referances

.1http://www.acuvue.co.in/acuvue-life/health-file/about-your-eyes/physiology-of-the-eye.html

.2http://www.ncbi.nlm.nih.gov/pubmed/673339

.3http://palopticlub.com/vb/forumdisplay.php?f=10

.4http://dare.ubvu.vu.nl/handle/1871/10864.5http://en.wikipedia.org/wiki/

Corneal_keratocyte

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