Cornea and Sclera Development Flashcards
Inductive mechanisms of cornea development
- pax6 gene locus is transcription factor for the various
- developing lens necessary to act as inucer for ectoderm to transform into cornea
- morphogenesis requires coordinated cellular events: migration, proliferation, and differentiation
Overview of cornea development
Surface ectoderm => presumptive corneal epithelium
Mesenchyme => neural crest mesenchyme => corneal endothelium and stroma
Surface Ectoderm (5-6th week) => presumptive corneal epithelium
ECM-tissue interactions
initiated when lens vesicle separates from surface ectoderm
surface ectoderm: presumptive corneal epithelium (2 layers):
Primary Stroma
produced by primitive corneal epithelial cells
acellular matrix: collagen fibrils, hyaluronic acid and GAGs
hydration of hyaluronic acid causes swelling to create space for cellular migration
directional membrae to guide the migration of neural crest cells
1st wave Mesenchymal components produces what (7th wk)
the 1st wave of neural crest mesenchyme produces the corneal endothelium
1st wave mesenchyme: neural crest mesenchyme at anterior tip of optic cup
- migrates to form single layer in front of lens
- presumptive corneal endothelium
2nd wave mesenchymal components produces what (8th wk)
2nd wave of neural crest mesenchyme produces secondary cornea stroma.
2nd wave of neural crest mesenchyme invades primary stroma at margin of optic cup
-do not invade anterior 10 um primary stroma => becomes bowman’s layer
cornea stroma production
neural crest cells proliferate and differentiate into keratoblasts:
- synthesize type 1 collagen fibrils and GAGs
- layers fill in from posterior to anterior stroma
corneal stroma differentiation
process begins in posterior stroma and progresses anteriorly
-collagen lamellae: 1st organized in posterior stroma
keratoblasts differentiate into keratocytes
collagen and lamellae create most of stroma, but initally started by these keratoblasts
Descemet’s membrane development
endothelial cells produce basement membrane
DM seen 8wks and matures at 4 months
innervation development
tissue of origin of innervation: neural crest cells
3-5 month: first seen
6-9 month: nerve inc. in number and form network
supplied by CN5 V1
Fusion of eyelids and development
Eyelids fuse at 9th wk
in 24 weeks, eyelid open: cornea epithelium increase thickness and differentiates to basal, wing, squamous cells
factors affecting corneal size, curvature, transparency
Eyelid fusion: transparency gradually achieved due to maturation of stromal lamellae, metabolic activity of endothelium dehydration of cornea
cornea at birth and postnatally
newborn diameter: 9.5-10mm
diameter reaches adult size at 2 years of age
newborn radius of curvature: 47.00 (STEEEP)
-flattens with age
at birth: cornea may be thicker than adult (caused by increased water content caused by underdeveloped endothelial ion transport)
cornea translucent during fetal period
Sclera development tissue origin
neural crest: 95% of sclera
mesoderm: small portion from paraxial mesoderm
scleral development inductive mechanisms
- RPE influences scleral development (neural crest differentiation)
- IOP and vitreous formation: determines scleral shell size (expansion from IOP, increased vitreous volume)
Scleral development timeline
7th week - scleral condensation– limbus
8th week - equator
3rd month - optic nerve
5th month - lamina cribosa
develops anterior to posterior
scleral condensation
anterior to posterior development
neural crest cells differentiate to fibroblasts
fibroblasts: collagen, elastic fibers, and GAGs
neuro crest cells meet myoblasts of EOMs
neural crest cells form sheaths for muscle fibers near equator of globe
Fibroblasts synthesize what
collagen fibrils - initially small diameter that steadily increases
elastic fibrils
proteoglycans and GAGs (13 wk)
postnatal scleral development
birth: sclera thin, highly distensible, translucent
postnatal: collagen synthesis most active in posterior eye
diameter of fibers and rigidity change: outer scleral layers (larger diameter) collagen fibrils compared to inner layers (smaller)
- response to circumferential streses on scleral by IOP
- regional differences in fibril diameter likely contribute to scleral resistance to IOP
sclera increases diameter and thickness in relatively rapid manner, loses distensibility during first 3 years
growth continues at a slow pace after 3 years:
anterior sclera adult size by age 2
posterior sclera develops until age 13-16
differences between cornea and sclera development
cornea development:
- derived from surface ectoderm and neural crest mesenchyme
- induced by lens
- formed by 1st and 2nd waves of neural crest mesenchyme that migrates anteriorly with a guiding matrix of primary stroma with a resulting regular lamellar arrange ment
sclera development:
- derived from neural crest mesenchyme and some mesodermal mesenchyme
- induced by RPE
- formed from scleral condensation that migrates posteriorly with a resulting irregular interweaving arrangement
differences between developed cornea and sclera
cornea - transparent
- regular lamellar arrangement
- uniform fibrils with uniform diameter
- regularly spaced with regular size
- less interweaving and regular directed bundles
- steeper curve – clear cap on front of eye
- lacks elastin components
sclera - opaque
- irregular lamellar arrangement
- more nonuniform in diameter
- more irregularly spaced, arranged in variously sized
- high interweaving, irregularly directed bundles
- flatter curve-opaque covering of eye
- elastin components
Cryptophtalmos
absent cornea
- facial skin replaces eyelids, covers orbit, obliterating cornea
- bilateral
- associated with other congenital birth defects
megalocornea
megaocornea newborn: 12 mm (normal 10 mm)
in adults: >13 mm (normal 12 mm)
-hereditary or secondary to congenital glaucoma
megalocornea - hereditary
resulting from anomalies of differentiation of neural crest
greater than normal steepness (myopia)
defect in growth of optic cup
typically isolated but many ocular and systemic associations
megalocornea - 2nd to congenital glaucoma
buphthalmos - ox eye
- elevated IOP stretches cornea and sclera
- ocular enlargement
- descemet’s may rupture or tear
- -haab’s stria: old, healed horizontal ruptures in descemet’s
- -curved lines or scars at endothelial level (tend to be horizontal)
other findings with congenital glaucoma: tearing, photophobia, blepharospasm
microcornea
horizontal diameter < 10mm
nonprogressive, can be unilateral or bilateral
flat cornea
2 proposed cause:
1) arrest in growth of cornea (after 5th gestational month)
2) overgrowth of anterior lips of optic cup
sclerocornea
non-progressive
cornea opaque and limbus indistinct
corneal flat (< 43 D)
cornea plana
cornea curvature < scleral curvature
occur alone or with other ocular defects
usually bilateral, commonly asymmetric
caused by abnormailty of 2nd wave of mesenchyme (severity variable)
central cornea usually clearer than periphery (differnt than peter’s anomaly)
posterior corneal defect (peters’ anomaly)
- rare, sporadic and frequently bilateral disorder
- range of severity, from barely detectable focal indentation to total corneal scarring and ectasia
- results from delay or failure of separation of lens vesicle from surface ectoderm
- results in adhesion between cornea and lens
–migration of mesenchyme is impeded by this adhesion, causing characteristic features of this anomaly
peter’s anomaly characteristic features
opacity of central cornea
central concave defect in posterior corneal stroma
corneal endothelium and descemet’s membrane absent in posterior ulcer
lens adheres to cornea
iris adheres to cornea (iridocorneal adhesions)
severe form: corneal staphyloma, scarring, ectasia
tears in endothelium and desecemet’s membrane
birth trauma: vertical or oblique lines in inner corneal layers
congenital glaucoma: haab striae: horizontal breaks or circumferential breaks
corneal dystrophy
occur early in life
familial inheritances - AR or AD
bilateral, central cornea involved
- almost all autosomal dominant
- not associated with any other systemic diseases
- onset of dystrophy is by age 20
- bilateral
- slowly progressive
- primary involved in a single cornea layer (either epithelium, stroma, endothelium)
anterior corneal dystrophies
corneal epithelium
epithelial basement membrane
bowman’s layer
epithelial-basement membrane dystrophy (EBMD)
most common anterior corneal dystrophy
abnormal basement membrane synthesized
onset 30-40
central
3 patterns:
maps - gray epithelial patches: islands of anomalous basement membrane
dots - multiple intraepithelial cysts + cellular debris; intraepithelial opacities
fingerprints - gray or refractile fine lines; basement membrane separating sheets of duplicated epithelium
stromal dystrophies
abnormal substances appear within keratocytes or among collagen fibrils
- Granular (hyaline)
- Lattice (amyloid)
- Macular (GAGs/ MMP)
mnemonic: Mickey Mouse Goes Home to LA
granular dystrophy (hyaline deposits) - stroma
hyaline deposits in anterior stroma
gray-white opacities do not extend to limbus
visual loss relative late
in life
macular dystrophy (GAGs deposits/MMP deposits) - stroma
least common, most severe
begins as central gray-white superficial stromal opacities
clear corneas that cloud between age 3-9
autosomal recessive
accumulation of GAGs
lattice dystrophy (amyloid deposit) - stroma
most common stromal dystrophy
localized amyloidosis
glasslike branching lines in stroma, seen best with retroillumination
autosomal dominant
Endothelial dystrophy: Fuch’s endothelial dystrophy
thickening of descemet’s membrane (corneal guttata: droplets)
compromise of endothelial fxn
corneal edema
rare symptomatic before 50
corneal decompensation
marked stromal edema
microcystic and bullous epithelial edema
subepithelial fibrosis
anterior keratoconus - ectatic dystrophy
- progressive thinning of central stroma
- leads to conical configuration of cornea
- present in teens
- bilateral, central, and slowly progressive
- munson’s sign - pushes on lower lid when looking down
- fleisher’s ring (iron) in deep epithelium and BM at base of cone
- vogt’s lines (vertical striae/stress lines)
- stromal thinning
- acute hydrops (stromal edema
- scissors reflex in ret
