Date post: | 13-Aug-2015 |
Category: |
Health & Medicine |
Upload: | lhacha |
View: | 36 times |
Download: | 1 times |
Anatomy and Physiology of cornea
Dr.Lhacha Wangdi
1st year Resident
Department of Ophthalmology
JDWNRH/KGUMSB
Outline
Gross anatomy of cornea -Surface anatomy -clinical applicationMicroanatomy of cornea -anatomy of ultra structurePhysiology of corneal tissue
Introduction
Word cornea originated from Latin word-
Cornu (horn) Cornea tela(horny tissue)
Transparent avascular tissue with a convex anterior surface & concave posterior surface.
Main function is OPTICAL
Other functions are: -STRUCTURAL INTEGRITTY -PROTECTION FOR THE EYE
Gross anatomy of corneaCovers the anterior scleral foramenLimbus is transition zone between
cornea and scleraThe cornea protrudes slightly beyond
the scleral globe because of the different curvatures of the two structures
Radius of curvature (cornea)–6.7-9.4mm whereas scleral-11.5mm
Cornea appears elliptical in shape measuring 11-12mm horizontally and 10-11mm vertically
Surface area: About 1.3 cm² (one-sixth of the
globe)
11-12mm
10-11mm
limbus
Corneal thicknessPosterior surface of cornea is
curved more than anterior surface
Central zone- 0.52mm Paracentral zone- 0.52-
0.57mm(outer diameter-7-8mm)Periphery zone- 0.63-0.67mmThe thinnest zone is 1.50mm
temporal to the geographic center about 0.505-0.51mm
In endothelial/ epithelial cell dysfunction, corneal becomes unusually thick due to stromal edma
Thick cornea will give false IOP reading
Surface anatomy- corneaCornea is not a true sphereIt has a central spherical
(optical zone-4mm)with uniform flattening towards the periphery –prolate shape
Flattening is more extensive nasally and superiorlySurface cornea is divided into three zones-
1. Central zone of 1-2mm-spherical(red area)2. Paracentral zone of 3-4mm around the
central zone with progressive flattening3. Peripheral zone which is flattened more.
Clinical application-
1. Topographic information of
cornea is important in contact lens
fitting2. Flattening of
cornea at periphery helps to
reduce the spherical
aberration of optical system
3. Alteration of the uniform curvature of cornea will induce astimatism
Spherical aberrationIn total spherical object
peripheral parallel rays of light refract more and focus in front of ideal image point.
Effects- blurred vision
Spherical aberration is minimized by aspheric (prolate) shapes of eye surfaces- due to peripheral flattening
Cornea as a optical system
Main function of cornea- optical( refraction of light for clear vision)
Contributed by its special characteristics; 1. Transparency 2.Avascularity 3. Controlled hydration 4. High refractive power The optical power of the cornea=42.0 D Is equal to 2/3 of the total optical power of the human eye (57 – 62
D)
Refractive power of cornea=(refractive index of cornea-refractive index of air)
(radius of curvature of cornea)Refractive index of cornea is more -Cornea- 1.33765 -Air- 1.000Radius of curvature is inversely proportional to curvature: - Anterior surface – about 7.8 mm -Post. Surface – about 6.5 mm
Microanatomy of corneaCornea has five defined layers
1. Epithelium and basal lamina-5% of thickness
2. Bowman’s layer3. Stroma-90% of total
thickness4. Descemet’s Membrane5. Endothelium –single
cellular layer (germinal layer)
Composition of corneaWater: 78 %Collagen: 15 % of which: Type-I : 50-55 % Type-III : 1 % Type-IV : 8-10 % Type-VI : 25-30 %Other protein: 5 %Ground substances -Keratan sulphate: 0.7 % -Condroitin/dermatan sulphate: 0.3 %Hyaluronic acid: +Salts: 1 %
Embryonic origin of cornea
Clinical significance-cell line originating from surface ectoderm has regenerative capacity whereas those from neural crest has little regenerative capacity
Disease affecting other organ such as in atopic dermatitis may cause keratitis due to similar embryonic origin
Epithelium-Derived from surface ectoderm
Bowmans layer-mesenchyme(neural
crest cell)
Endothelium-mesenchyme(neural crest cell) 1st wave
Stroma -mesenchyme(neural crest cell) 2nd wave
descemet’s – synthesised by endothelium
Epithelium Derived from surface ectodermConstitutes of 5-6 layers of cell accounting for
about 5% of corneal thickness-(0.05mm/50um)
Its has three cell layers1. Apical cells-
nonkeratinised Squamous epithelium
2. Wing cells- 2-3 layers of polygonal cell
3. Basal columnar cells (germinative layer)
Nonepithelial cells- histocytes, macrophages, lymphocytes, antigen presenting langerhans cells are also present which becomes more numeruous during keratitis
Ultrastructure of epithelium
Apical cells layers consists of 2-3 layers of flattened hexagonal cells
Surface cells contain microvilli & microplicae coated with 300-nm thick glycocalyx/glycoprotein (buffy cell coat)The mucin layer of tear binds with glycocalyx
and helps in uniform spreading of tear film,
Ctn…Epithelial cells are adhered together by tight junctions –
1. Tight junctions & desmosomes – surface cells
2. Desmosomes – wings & superficial cells
3. Desmosomes & Hemidesmosomes – in basal cells
4. Cells are anchored to deeper tissue by anchoring proteins
Functions- 1. Maintains corneal homeostasis(impermeable to Na ions & confer
semipermeable membrane properties to the epithelium)2. Mechanical barrier – protective function against infection/toxins3. Tight junction ensure corneal transparency 4. Anchor epithelial cells to basal lamina and bowmans layer
Anchoring protein
desmosome
hemidesmosomes
Basal lamina Fibrous layer consisting of 1V collagen and glycoprotein.
Secreted by the basal cells 0.5 - 1 μm wide Ultra structurally it is
distinguished in to two parts1. Lamina lucida (superficial)-
electron lucen zone 2. Lamina densa (deep electron
dense zone)3. Anchored to bowman’s layer with
numerous anchoring fillaments
Lipid solvent, stromal oedema and inflamation may loosened the cohesion between Bowman’s zone,lamina and epithelial cells-– eg mucus filaments due to epithelial instability
With old age, in diabetes and in some corneal disorders it becomes thickened and multilamellar
Epithelial regeneration
The epithelium is constantly in a state of turn-over with exfoliating apical cells being replaced by underlying wing cells-weekly
Basals cells are only epithelial cells capable of mitosis
During normal apical cell exfoliation basal cells proliferates and replace lost cells in 7-14 days
Loss of basal cells and defective regeneration will lead to corneal scar formation
Apical cells loss
Wound healing
During epithelial defect either due to infection/trauma/inflamation there are extended proliferation and differentiation of basal cells
If Boman’s layer is intact the epithelium is regenerated in 7-14 days
Cellular events
Repair of corneal epithelial injury like abration/infection follows a distinctive sequence of events-1. Cells at wound edge retract, thicken
and lose attachment, produce various growth factors (egTGF-Bs)
2. Basal cells travel in an amoeboid movement to cover the defect
3. Migration process is halted by contact inhibition
4. They then anchor by secreting basal lamena
5. Mitosis resumes to re-establish epithelial thickness
6. Surface tight junctions re-establised7. Adhesion with Bowman’s layer
within 7 days (if basal lamina intact)8. The healing process occurs rapidly,
rate of cell migration is 60 – 80 μm/hr
Toxin, trauma,
infection, inflammatio
n
Spreading and dedifferentiati
on
Cell migration
Cell proliferation
Regeneration
redifferentiation
Germinative cellsIt is now recognized that
the germinative region lies at the limbus
Limbal stem cell migrate centrally to replace corneal epithelial basal cells
The stem cells migrate at a very slower rate (123 μm/week) to the center of the cornea which may be as long as a year
Loss of limbal stem cells will result in corneal scar
Limbal stem cells
The XYZ hypothesisRichard A. Thoft & Judith Friend(1983) proposed on
the basis of experimental evidence that both limbal basal and corneal basal cells are the source for corneal epithelial cells. The corneal epithelium is maintained by a balance among-
(Z)Sloughing of cells from the corneal surface is = (X)cell division in the basal layer + (Y) Migration of basal cells originating from the limbal stem cells
Ctn.. In normal healthy cornea there is a constant balance between; (cell turn over=regeneration)Regeneration= balanced basal cell proliferation +
migration+maturation+secretion of basement membrane+regeneration.
Abnormality of epithelial Cell turn over and regeneration causes epithelial opacity and haziness.
Example, Corneal Epithelial Basement membrane Dystrophy(EBMD) aslo called ‘map dot finger print’/’cogan microcystic dystrophy’
chateractised by; -dots/epithelail microcysts
(due to abnormal epithelium) -fingerprint/geographic map lines (due to thicken basement membrane)
Bowman’s layerModified region of anterior stroma8 – 14 μm thickAcellular homogeneous zone It is perforated by many nerve
axons which courses through toward the epithelium
Ant. surface is smooth & parallel with corneal surface
Posteriorly it becomes blended & interweaved with fibrils of ant. stroma
Functions- 1. Anchoring site for epithelial cells to ensure its stability2. Tough acellular layer provide mechanical supports3. Prevents stromal keratocytes from exposure to epithelial
growth factors- prevents keratocytes metaplasia to fibroblast and scar formation
Ultrastructural featuresUltrastructurally it is a
meshwork of fine collagen fibrils of uniform size in a ground substance (glycoprotein &proteoglecan)
Compact arrangement of collagen types I, III, V, and VI
it has great strength and relatively resistant to trauma both mechanical and infective
It is acellular and lacks fibroblast therefore after injury it is unable to regenerate- replaced by course scar tissue
Stroma About 450- 500 μm thick (about 90% of corneal thickness) Transperant and rich in collagen-predominantly of type I
collagen with types III, V, and VI also in evidence.
Proteoglycan(glycosaminoglycan)ground substance between the collagen fibers
5% of stromal volume occupied by keratocytes which synthesizes both collagen and proteoglycan
stroma
Stromal lamellaeStroma ensure transparency
of cornea by lamellar arrangement of collagen bundles
Stroma has about 200 layers of lamellae
Lamelae are arranged regularly almost right angle to each other
Each lamellae consists of bundle of collagen-
1. 200 – 300 bundles – centrally 2. 500 bundles – peripherally3. Width about 9 – 260 μm4. Thickness about 1.15 – 2 μm
Ultrastructural featuresEach lamellae comprises of a
band of collgen fibrils arranged in parallel with each other
Fibrils are regularly placed
each other with center-to-center distance of 55-60nm.
There is a unique uniformity of fibril diameter of 22 (±1) nm from ant. to post.
Regularly arranged lamellae with uniform diameter and seperation of collagen fibers makes cornea transparent
Ground substances of stroma The ground substance of cornea consists of
proteoglycan that run between the collagen fibers
It constitutes approximately 10% of corneal weight
Proteoglycan are glycosylated with glycosaminoglycan(GAGs)-disaccharides
GAGs include- 1. Keratin salphate 2.Chondroitin sulphate 3.Dermatan sulphateFunction- 1. Confer hydrophilic properties of stroma2. Maintains corneal transparency by controlled stromal
hydration by contributing fixed negative charge of stroma (normally stroma is 78% hydrated)
3. Helps in regular spacing of collagen fibers to ensure transparency
Cellular components of stromaKeratocytes: Long, thin, flattened cells (maximally 2μm
thick) running parallel to corneal surface Position – between the lamellae Having long flattened nuclei, sparse
cytoplasm but contains full component of organells
Function 1. responsible for synthesis and maintaining
of collagen & proteoglycan substance of stoma
2. helps in corneal regeneration after injury3. Part of corneal anti-oxidant
defense(proteinase inhibiter, inhibitors of metalloproteinases e.t.c) Other cells-
Lymphocytes, macrophages and polymorphonuclear leucocytes (very rarely) also found in stroma ocationally- becomes numerous in corneal ulcer/stromal abscess
Stromal transparency theoryThe cornea transmits nearly
100% of the light that enters it. Transparency achieved by –
Two theories –i) Maurice (1957): The transparency of the
stroma is due to the lattice arrangement of collagen fibrils.
He explained, because of their small diameter and regularity of separation, back scattered light would be almost completely suppressed by destructive interference
Ctn…
ii) Goldman et al. (1968): He suggest, a perfect crystalline lattice
periodicity is not always necessary for sufficient destructive interference.
He explained, if fibril separation(55-60nm) and diameter(22nm)is less than a third of the wavelength of incident light,(400-700nm) then almost perfect transparency will ensue.
This is the situation which obtains in normal cornea.
Other factors of corneal transparency
1. Epithelial non-keratinization 2. Regular & uniform arrangement of
corneal epithelium 3. Junctions between cells & its
compactness and also tear film maintain a homogenicity of its refractive index
4. Relative controlled hydraton of normal cornea
5. Corneal avascularity 6. Non myelenated nerve fibres
Descemet’s membrane It is the basal lamina of corneal
endothelium -First appears at 2nd month of gestation
and synthesis continue throughout adult life
Thickness – at birth (3-4 μm) adult (10 – 12 μm)It has two zones-Anterior 1/3 zone - developed in utero -irregular banded zone Posterior 2/3 zone -developed after birth - Homogenous fibrillogranular material It is a strong resistant sheet -Major protein of DM is Type IV collagen
Ctn…. Due to aging ther can be
focal overproduction of basal lamina- peripheral excrescence called Hassal-Henle warts
No clinical abnormality in corneal function
In extensive stromal thinning eg. in corneal ulcer descemet’s membrane may bulge forward to form desmatocele
Ctn…The peripheral rim of DM is
the internal landmark of corneal limbus
It is the anterior limit of drainage angle, is called Schwalbe’ line
Schwalbe’s line may hypertrophied in congenital anomalies and appears as visible shelf on gonioscopy, is called posterior embryotoxon
Endothelium It is a single layer of hexagonal,
cuboidal cells attached to posterior aspect of DM
It is nuroectodermal in origin Corneal endothelial cells
production is relatively fixedIt is about 500000
(2500cells/mm2)
Endothelial cells density – -At birth-About 6000 cells/mm² -26% lost in 1st year -Further 26% lost over next 11 years -Rate of cell loss slows and stabilizes around middle age and then it is about 2500 cells/mm²
Ultrastructural featuresSingle oval nucleus located centrallyEndothelium is rich in subcellular
organeles – large number of mitochondria, both rough and smooth endoplasmic reticulum, free ribozomes, these reflects that endothelium is extremely active metabolically
The posterior cell membrane (Apical) facing Anterior chamber shows 20-30 microvilli- increases absorption areaCellular junction-1. The anterior cell membrane (Basal) is
attached with DM by modified hemidesmosomes
2. Ant. 2/3rd – maculae adharentes3. Post. 1/3rd & apicolateral edges –
macculae occludentes
Endothelial functions
a)Maintains corneal hydration(slightly dehydrated stae-78% hydration) by ‘pump-leak hypothesis’-1. Providing physiological barrier to salts and
metabolites to stroma. 2. Active transport transport of bicarbonate by
Na+/K+ATPase actively removes H2O from stroma by pump action.
NA+/K+ATPase is located at the endothelial cell membrane
Using ATP, the pump actively transport Na+, K+ and bicarbonate to the AC
Creats + osmotic gradient in the aqueous
H2O moves from stroma to AC
NA+/K+ATPase failure
Failure of NA+/K+ATPase to maintain corneal hydration will cause;
- stromal edema, -subepithelail fibrosis -epithelial bullae -corneal guttata
Example- Fuchs endothelial dystrophy
Endothelial function ctn..
b)Injury and repair-Endothelial cell regeneration is not possible by
mitosisHealing occurs by cell enlargement.Immediately after injury; 1.Descet’s membrane retracts and injured endo.cell detaches. 2. fibrin clots formed at wound 3.within hours adjacent endo.cell attenuate with cytoplasmic processes 4.migrate to wound site 5. cellular reorganization and enlargement- reconstitute monolayer (completes by 1-3 days)
Ctn….Endothelial decompensation will cause stromal
edema, reduced transparency and loss of visionEndothelial decompensation occurs when cells
density falls upto 500 cells/mm² .
With advancing age the endothelial cells become polymorphic in shape due to cell enlargement during repair
Corneal Nutrition & Metabolism
Glucose, amino acid, vitamins, and other nutrients supplied to cornea by aqueous humor, a lesser amounts from tears or limbal vessels
Glucose also derived from glycogen stores in corneal epithelium
Glucose is metabolized in cornea by three metabolic pathways;
1. Tricarboxylic acid cycle(TCA)- epithelium & endothelium
2. Anaerobic glycolysis- when there is lack of O2
3. Hexose monophosphate(HMT) shunt –mainly in endohelium
Ctn..During normal aerobic metabolism end product of
glucose- pyruvic acid is converted to H2O via TCA cycle.
During anaerobic state as in tight contact lens lactic acid is produced via anaerobic glycolysis which causes
1.Stomal acidosis, 2.Edothelial cell dysfunction 3.Corneal edema and visual impairment
Oxygen – mainly from atmosphere through tear film, with minor amounts supplied by the aqueous and limbal vasculature
Nerve supply of CorneaCornea is rich in
sensory nerve supply derived from ophthalmic division of trigeminal which give branch to;
- Nasociliary nerve and -Ciliary nerves (terminal branch)
Ciliary nerve enter the pericoroidal space a short distance behind the limbus.
60-80 myelinated branches pass into cornea
Ctn… 1-2 mm from the limbus nerves axon lose myelin sheaths and divide into;
- anterior branche -posterior banche Anterior nervs (40-50) pass through stroma and form plexus subjacent to Bowman’s layerNerve fibres then penetrate
Bowman’s layer and form subepithelial plexus
Fibres then divide dichotomously to form a parallel network which run for upto 2 mm
Free nerve terminals finally supplies superficial epithelial layers
The posterior groups of nerves (40-50) pass posteriorly to
innervate the posterior stroma excluding Descemet’s membrane
Subepithelial plexus
Anterior posterio
r
Ctn…
HSV infection of cornea spreads along the nerve axons
Involvement of terminal nerve causes;
-dendritic appearance - loss of corneal sensation
Nerve innervation is important to maintain balanced epithelial cell division
Lesion of fifth nerve will cause abnormal cell turn over and loss of reflex tearing and leads to Neurotrophic keratitis
References
Yanoff & Duker Ophthalmology- 4th edition
American Academy of Ophthalmology Jack J. Kanski Clinical ophthalmology- 7th
editionOxford textbook of ophthalmologyJournal- Association for Research in
Vision and OphthalmologyDuane’s clinical ophthalmologyImages and graphics- internet sources