The Cornea.pdf

The Cornea Karen Gil MD, MHSN Corneal Development • 6th week - Corneal epithelium develops from the surface ectoderm • Neural crest cells (mesenchymal cells) contribute to the formation of the corneal stroma (which produces Bowman’s layer) and the corneal endothelium (which produces de Descemet’s...

The Cornea Karen Gil MD, MHSN Corneal Development • 6th week - Corneal epithelium develops from the surface ectoderm • Neural crest cells (mesenchymal cells) contribute to the formation of the corneal stroma (which produces Bowman’s layer) and the corneal endothelium (which produces de Descemet’s layer) Corneal Development 7th month adult corneal structure is establish Cornea • Outer connective tissue coat of the eye: – Cornea (anterior) • Smaller anterior transparent sphere • Radius of curvature approximately 8mm – Sclera (posterior) • Larger posterior opaque sphere • Radius of approximately 12 mm • The globe is not symmetric, diameters: – 24mm anteroposterior – 23mm vertical – 23.5 mm horizontal Cornea • • • • • Thin Transparent Toric structure Five layers Fits into the anterior scleral foramen • The refractive power is 45D Corneal Dimensions • Viewed from the front the cornea appears oval and from behind appears spherical • Anterior horizontal diameter – 12mm • Anterior vertical diameter – 11mm • Posterior horizontal and vertical diameters – 11.7 Corneal dimensions • Has an elliptic shape • Radius of curvature of the central cornea: – the anterior surface is 7.8 mm – the posterior surface is 6.5 mm Corneal dimensions • Central cornea thickness is 0.53 mm • Corneal peripheral thickness is 0.71mm (approximately) Corneal Histological Features • Principal refracting component of the eye • Transparency and avascularity provide optimal light transmittance • Anterior surface covered by tear film • Posterior surface borders the aqueous-filled anterior chamber • Its periphery continuous with the conjunctiva and the sclera Corneal layers • From anterior to posterior • Five layers: 1. Epithelium (50 μm) 2. Bowman’s layer (8-14 μm) 3. Stroma (500 μm) (Dua’s Layer 3-15 μm)* 4. Descemet’s membrane (5-15 μm) 5. Endothelium (5 μm) Corneal Epithelium • Outermost layer • Stratified squamous nonkeratinized epithelium • 5 to 7 cells thick • Measures approximately 50 μm • Thickens at the periphery and is continuous with the conjunctival epithelium at the limbus Corneal Epithelium • Three different layers of the epithelium 1. Surface layer 2. Wing cells 3. Basal layer Corneal Epithelium • Surface layer – 2 cells thick – Nonkeratinized squamous cells – The plasma membrane secretes glycocalyx – Contain microvilli that increase the surface area and enhance stability of the tears – As cells age, they are sloughed off into the tear film Corneal Epithelium • Surface layer: – Tight junctions: • Zonula occludens (tight junctions) • Adherens junctions • Desmosomes (macula adherence) • Gap junctions – Provide tight barrier between the cells to impede intercellular movement of substances from the tear layer and prevent the uptake of excess fluid from the tear film – Highly effective semipermeable membrane (fluid and molecules pass though the cells but not between them) Corneal Epithelium • Wings cells: – 2-3 cells thick – Have wing like lateral processes – Polyhedral – Convex anterior surface, concave posterior surface (fit basal cells) – Desmosomes join these cells together and to surface and basal cells Corneal Epithelium • Basal layer: – single layer of columnar cells – Is the germinal layer (mitosis) – Secrets its own basement membrane and attaches to it via hemidesmosomes – The basement membrane of the basal layer attaches to the underlying Bowman’s membrane via hemidesmosomes that penetrate Bowman’s and attach to extracellular matrix within the stroma Corneal Epithelial Replacement • Cell proliferation occur in the basal layer • Basal cells move up to become wing cells • Wing cells move up to become surface cells • Only the cells in contact with the basement membrane have the ability to divide Corneal Epithelial Replacement • Stem cells located in a 0.5 to 1 mm wide band around the corneal periphery • Stem cells are the source for renewal of the corneal basal cell layer • Migration of basal cells occurs form the periphery toward the center of the cornea • Turn over time for the entire corneal epithelium is approximately 7 days • Minor abrasions heal within hours, larger ones overnight • Damage basement membrane need months to complete healing The basal epithelial cells of the cornea, which undergo vertical proliferation (both daughter cells move into the middle layers of the epithelium) are continually replenished by a stem cell population that resides in basal layer of the limbus. The transient amplifying (TA) basal epithelial cells, which are two horizontal progeny from the stem cells, migrate forward from the limbus to the periphery of the cornea and commonly to reach the center of the cornea. The TA undergo mixed (one daughter cell retained in the basal cell layer and the other moves into the middle layers of the epithelium) proliferation. The final or terminal cell cycle of mitosis is the vertical proliferation step, where the two daughters continually move toward the surface eventually being shed in the tear film. (Modified from Thoft RA et al. Invest Ophthalmol Vis Sci 1983; 24:1442) Corneal Bowman’s Layer • Acellular dense layer composed of random collagen fibrils (20-25 μm) • Is not a membrane is a transition layer into the stroma • Approximately 8-14 μm thick • Is prenatally produced so cannot be regenerate (replaced by epithelial cells or stromal scar tissue) • Corneal nerves pass tough Bowman’s layer lose their Schwann cell covering Corneal Stroma • Also kwon as Substantia Propria • Approximately 500 μm tick • 90% corneal thickness (75-80% water) • Composed of: – Collagen fibers – Keratocytes – Extracellular ground substance (GAG substances) Corneal Stroma • Collagen Fibers – 25 - 35 μm diameter – Join and form 200-300 parallel layers called lamellae – Collagen type I,III,V and VI – Each fibril runs form limbus to limbus – Each lamella extends across the entire cornea – Posterior 2/3 of the stroma is more organized and shows a very regular pattern (latticework) and lamella become larger Corneal Stroma • Keratocytes: – Fibroblast of the cornea – Synthesize collagen and extracellular matrix components – Flattened cells that lie within and between the lamellae – Other cells can be found between lamellae • • • • WBC Lymphocytes Macrophages PMN – increase in pathologic conditions Corneal Stroma • Ground Substance: – Fills the areas between fibrils, lamellae and cells – Contains: • Proteoglycans – Macromolecules with a carbohydrate glycosaminoglycan (GAG) portion – Hydrophilic negatively charged carbohydrate molecules that attract water to create precise spacing between the lamellae – One reason for the relatively high stromal hydratation – Keratin sulfate (66%) of GAG’s in the cornea – Chondroitin/Dermatan sulfate (CS/DS) Corneal Stroma • The very regular arrangement of the stromal component and the small diameter of the fibrils contributes to stromal transparency Corneal Descemet’s Membrane • True basement membrane of the endothelium • Produced constantly and therefore thickens throughout life (age 40 doubled size) • Children is 5 μm tick • Increase to approximately 15 μm over a life-time Corneal Descemet’s Membrane • Consist two laminae 1. Anterior 3μm thick (banded appearance) 2. Posterior (nonbanded and homogenous) • Very resistant to trauma and damage a-depest corneal stromal lamellae b-Descemet´s layer c-endothelium Corneal Descemet’s Membrane • A thickened area of collagenous connective tissue may be seen at the membrane’s termination in the limbus – circular structure called Schwalbe’s line Corneal Endothelium • Innermost layer • Simple Squamous endothelial layer • Single layer of flattened cells • 5 μm thick • Basal part of each cell rests on Descemet’s membrane • The apical suface (microvilli extend) lines the anterior chamber Corneal Endothelium • Endothelial cells are polyhedral: five sided and seven sided cells (found normal cornea) • 70-80% are hexagonal • Regular arrangement of these cells described as: endothelial mosaic Scanning electron micrograph (×1000) of the posterior surface of the corneal endothelium from a 65year-old patient with healthy corneas. Note how the hexagonal endothelial cells form a uniform monolayer with small 20 nm intercellular spaces between adjacent endothelial cells. E = endothelial cells. IS = intercellular space. Adler’s physiology of the eye, cornea and sclera. Corneal Endothelium • Cells contain Na/K ATP pumps to regulate water and ion flow from aqueous • Cells are rich in organelles and mitochondria and are essential for maintaining corneal hydratation and correct lamellae spacing • Loose mitochondria with age Corneal Endothelium • Endothelial cells are linked by – Tight junctions • Desmosomes • Weak barrier to allow aa, glucose and nutrients enter from the AH Figure 3. The corneal endothelium serves as a leaky barrier between the corneal stroma (anterior) and anterior chamber (posterior). Water passively moves from the ac into the stroma, while protein and Molecular Biology of Eye Disease other nutrients (such as glucose) are Andrew J. Hertsenberg, James L. Funderburgh, in Progress in Molecular Biology and Translational Science, 2015 actively transported by corneal endothelial Corneal Endothelium • Endothelial cells do not replicate • They wear-out with age and neighboring cells change shape (pleomorphism) and size (polymegathism) • Pumps become less effective and stromal swelling can occur Corneal Endothelium • Cell density (per unit area) decreases normally with aging because of cell disintegration • Density ranges: – Children 3000-4000 cells/mm2 – Adults 2500 cells/mm2 – Age 80 years 1000-2000 cells/mm2 – Minimum necessary for adequate function 400-700 cells/mm2 Very-highmagnificatio n slit lamp biomicrosco pe photograph s of (A) high and (B) low endothelial cell density. Corneal Layer at the Limbus • Epithelium –bulbar conjunctiva • Bowman’s – lamina propria of the conjunctiva • Stroma – Sclera • Descemet’s – Schwalbe’s line • Endothelium – lines the Trabecular Meshwork Corneal Function • Two primary functions: – Refract light – Transmit light • Factors that affect the amount of corneal refraction: – The curvature of the anterior corneal surface – The change in refractive index from air to cornea (actually the tear film) – Corneal thickness – The change in refractive index from cornea to aqueous humor Corneal Function • Total refractive power of the eye is between 60-65 D (diopters) • 43 to 48 D attributable to the cornea • Regularity of spacing between the collagen fibrils is important to maintain corneal transparency (stroma 90% cornea) Corneal Blood Supply • Avascular • Tree outer sources supply: – Diffusion form the aqueous humor – Limbal conjunctival and episcleral capillary networks – Palpebral conjunctival networks Corneal Blood Supply • Cia-anterior ciliary artery • ec- episcleral arterial circle • ca-conjunctival artery • ep-episcleral capillary plexus • cp- conjunctival capillary plexus • la-limbal arcades • cv-conjunctival vein (From Meyer PAR, et al. Low dose fluorescein angiography of the conjunctiva and episclera. BJO 71:2, 1987.) Corneal Innervation • V1- Ophthalmic nerve innervates the cornea (first division of the trigeminal nerve) • Nasociliary nerves form long posterior ciliary nerves, this form a myelinated network of 60-80 nerves and enter the midstroma Corneal Innervation • The network of 60-80 nerves and enter the Bowman’s layer loose they myelin sheath and become unmyelinated • More sensitive Corneal Innervation • Networks are formed in three places: – Epithelium – Anterior stroma/Bowman’s layer – Midstroma • All the nerves penetrates Bowman’s and enter the epithelium, they lose their Schwann cell covering and become highly sensitive “naked” nerves • No corneal nerves are located in Descemet’s layer or the endothelium