Embriologi

Mata
Muhamad Rifqy Setyanto

Importance
To understand the structure of normal adult
eye and its anatomic characteris.cs
the pathogenesis of numerous congenital
anomalies of the eye that may occur as a
result of defec<ve embryogenesis
The various diseases of the eye

3 elements have been iden<ed that regulate:

Growth Factors

Fibroblast growth factors (FGF)

Transforming Growth Factor- (TGF- 1 and TGF- 2)
Insulin like Growth factor-I (IGF-I)

Homeobox genes - DNA sequence found

within genes that are involved in the regula<on
of paMerns of anatomical development
(morphogenesis)
P PAX 6
P HOX (HOX8.1, HOX 7.1)

Neural crest cells

Synergis.c ac.on of these mul<ple trophic

factors appears to be a signicant regulatory
tool for :
Ini<a<ng cellular ac<vi<es and
For limi<ng abnormal development

 Neural plate
Ectodermal cells of
anterior por<on of
embryonic plate
proliferates + thickens
Neural groove
Medial longitudinal
furrow
Neural fold
Eleva<on at 2 sides of
the neuroectoderm
Neural Tube neural
folds meet at midline


At the anterior por<on of the neural
tube 3 dilata<ons are formed


The eye begins to develop as a pair
of op#c vesicles on each side of the
forebrain

Of the three germ layers of the embryo, only
two are involved in the development of eye
Ectoderm surface ectoderm

neuroectoderm
Mesoderm

EMBRYOGENESIS OF EYE
PRIMITIVE EYE starts
in 3rd week of gesta<on
when anterior por<on
of neural tube is
closing.
It origins as op.c pit
thickening on either
side of midline in the
ventrolateral region of
primi<ve forebrain

 The op<c pit enlarges to

form 2 globular structures
at either side Primary
Op.c Vesicles.
Which connects to the
forebrain via a n Op.c Stalk
Primary op<c vesicle meets
surface ectoderm

 During 4th week of gesta<on op<cal vesicle invaginates

distally and inferiorly forma<on of two layered op<c
cup
Op<c cup is widely open distally and inferiorly.
Invagina<on also involves the op<c stalk so this inferior
groove forms Op.c ssure/ embryonic ssure

Invagina#on of op#c vesicle

Rim of optic
cup

Lateral wall
of Forebrain

Embryonic ssure

Embryonic ssure
Closes at 6th week
Closure begins at centre and extends anteriorly and
posteriorly un<l only a small crescent remains open
at the posterior pole.

IMPORTANCE: Through the ssure there is

Outgrowth of axons from ganglion cells which form
the op<c nerve
Ingrowth of vascular elements which aids in
growth and development of the eye

Applied anatomy

Failure of fusion of this ssure - 6th/7th week
results in coloboma forma<on

PAnterior extreme Colobomas of iris

PPosterior extreme Colobomas of posterior
fundus and op<c nerve

Anterior and posterior aspects of cup are

open for longer <me hence it is exposed
longer to teratogenic insults

Coloboma op#c disc

Coloboma iris

RETINA
Develop from two layers of op<c cup

PSensory re<na is formed by the inner layer of op<c cup
PRe<nal pigment epithelium is formed by the outer layer of
op<c cup

Re.nal Pigment layer

It is a single layer of columnar cells
ini<ally it is non-pigmented but at 5th week
melanogenesis begins (Premelanosomesmelanosomes)
Dieren<a<on begins at posterior pole and proceeds
anteriorly

Neurosensory layer
PThe anterior 1/5th forms posterior surface of
developing ciliary body and iris
PThe posterior 4/5th ini<ally divided into-
inner marginal zone -devoid of nuclei
outer primi<ve nuclear zone which has 9
rows of nuclei

Later the outer nuclear layer invades the inner

marginal layer at the <me of closure of
embryonic ssure, so re<nal Neurosensory cells
divide into
Inner neuroblas<c layer which contains
ganglion cells, amacrine cells, muller cells

Outer neuroblas<c layer which contains

horizontal, bipolar nerve cells, rod and cone cells

These layers are separated by the Transient

nerve ber layer of Chievitz which later forms
the inner plexiform layer

The inner 9 layers of re<na are formed by merging

of these two cell layers
By the 8th month of fetal life all layers of re<na are
recognizable

 Ganglionic cells are the

rst cell of re<na to be
clearly dieren<ated
Cones outer segment
form - 5 month
Outer Rods segment
form - 7 month
photoreceptor cells
con<nue to form afer
birth so it develops the
ability for increasing
resolu<on and
sensi<vity

 Ora serrata is a wavy line, that lies between the small

non nervous layer near the edge of cup & large
photosensi<ve por<on in the inner layer of op<c cup
Macula has localized increase of superimposed nuclei
in the ganglion cell layer, lateral to op<c disc, in mid
term
Fovea centralis during 7th month, thinning of centre of
macula due to peripheral displacement of ganglionic
cells.
Ganglionic layer
Inner Nuclear layer
Outer plexiform layer/
Henles layer *
Foveal
Depression

Applied Anatomy
Areas where RPE does not form (some<mes along the
line of closure) the underlying choroid/sclera/
neurore<na is hypoplas<c
Re<nal detachment- Poten<al space between the inner
and outer layers of op<c cup is the site for re<nal
detachment.
Foveal region is extremely thin, devoid of ganglion cells
and retains rela<ve transparancy, allowing persistent
transmission of underlying highly vascular choroidal
hue eg. Cherry Red spot (Sphingolipidoses)
Juvenile Re<noschisis- splihng of the re<na in the
nerve ber layer.

OPTIC NERVE

Op<c stalk and op<c axons together form the op<c nerve.
Its the constricted elongated area between primi<ve eye and
forebrain
Ini<ally there is an inner zone (neuroectodermal cells) and
outer zone (undieren<ated neural crest)
6th weeksome cells of inner region vacuolate+ degenerate
+ remaining inner zone dieren<ates into glial cells.
Axons from ganglion cells run through the inner layer of stalk
Cells of inner layer encroach on the cavity of the stalk
cavity disappears
End of gesta<on Development of lamina cribrosa

Myelina<on of axons of op<c nerve begins just

before birth and con<nues some <me afer birth
Op.c disc- the point where the axons from
ganglionic layer of re<na converge to leave the
posterior surface of op<c cup along with the op<c
stalk
Op.c chiasma- par<al decussa<on of the axons of
the 2 op<c nerve
Op<c tracts
Lateral geniculate bodies
Tectum of midbrain

Applied Anatomy
Op<c nerve

Aplasia
Hypoplasia

Morning Glory Syndrome -

central excava<on surrounded
by an elevated rim of pink
neuroglial <ssue with the
vessels emerging radially from
the disc as spokes in all
direc<ons

Pit of the op<c disc

Lens
Begins development at 3rd week
Derived from surface ectoderm
Triggered by interac<on of forward growth of op<c
vesicle with surface ectoderm thickens and forms
lens placode

It invaginates to form lens pit that eventually

seperates + meets at the margin lens vesicle

CORNEAL EPITHELIUM
ANTERIOR WALL- single
layer of cuboidal
epithelium
POSTERIOR WALL-
increases in length and
form elongated bres
that projects into lumen
of vesicle (crystallin)
NUCLEAR BOW- nuclei
of the lens bers move
anteriorly to form a
convex line

 Nuclei disappears
Addi<onal lens bers are formed by mito.c division
of the anterior epithelial cells at pre-equatorial
region Secondary bers
These are formed through out life
Basal ends are aMached to the basal lamina while
apical ends extends to primary bers As the
bers are laid down concentrically laminar
appearance of the lens
New bres are added concentrically around the old
central bres around the equator

 Drawing shows
forma<on of the
lens vesicle and
op<c cup. The
op<c ssure is
present because
the op<c cup is
not fused
inferiorly.


Dierent layers seen in adult eye:
Embryonic nucleus- 1st to 3rd month of embryonic
life (Primary bers)
Fetal nucleus- 3rd to 8th month of fetal life
Infan.le nucleus- last weeks of fetal life to puberty
Adult nucleus- formed afer puberty
Cortex- recently formed bers, beneath epithelium
anteriorly, beneath capsule posteriorly


SUTURES The linear juncture where the bers
terminate and abut each other.
Y Sutures- begin to form 2nd month
PAnterior upright
P Posterior inverted

 Later in gesta<on and following

birth, sutures become complex
and dendriform.
LENS CAPSULE
PVascular lens capsule formed
from mesenchyme surrounding
the lens, Disappears afer birth
PTrue lens capsule formed
from Thickened basal lamina,
which develops from lens
epithelium.

 The Zonular Apparatus begins to

develop after the tertiary vitreous has
formed.
Ciliary Epithelial cells synthesize
collagen fibrils of the zonular fibers.
By 5th month increase in number,
strength and merge with the anterior
and posterior capsule.

Applied Anatomy
Unequal growth of bers from posterior wall +
New bers growing from equatorial regions
Ellip<cal shape of lens

If sutures are not formed and the bers meet at a
single point at anterior and posterior pole a pit
would be formed poor op<cal proper<es

Applied Anatomy

Lens epithelial cells lef behind in the capsular bag afer
ECCE PCO (posterior capsular opacica<on)
development.
PClinically 2 types of PCO,
Pbrosis type prolifera<on and migra<on of lens
epithelial cells, which undergo Epithelial-to-
Mesenchymal Transi<on brous metaplasia
producing folds and wrinkles in the posterior capsule.
Ppearl typeremnants located at the equatorial lens
region (lens bow) causes regenera<on of crystallin
expressing len<cular bers and forms Elschnig pearls
and Soemmering ring.

CONGENITAL CATARACTS

THE VITREOUS BODY

Develops between the lens and op<c cup
Primary vitreous forma<on at 1st month
P Network of delicate cytoplasmic processes
P derived partly from lens and partly from
re<nal layer of op<c cup and mesenchymal cells
P Supplied by hyaloid vessels and its branches
Secondary vitreous - forma<on at 2nd month
Between primary vitreous and re<na and is avascular
Derived from re<na and replaces the primary vitreous
extracellular matrix composed of type II collagen+
hyaloctes
Hyaloid vessels undergo atrophy hyaloid canal (5th
-6th mth-) cloquets canal which extends from op<c
nerve head and posterior surface of lens, Funnel
shaped

 Ter.ary vitreous- at 4th month

Between ciliary processes and lens capsule
Large no. of collagen bres develop with
forma<on of zonular bres

Applied Anatomy
Mittendorfs dot: remnants of anterior end
of hyaloid artery associated with posterior
polar cataract & attached to posterior lens
capsule.
Subluxation/Ectopia lentis: Partial or total
failure in Tertiary vitreous development
Bergmelsters Papillae: flakes of glial
tissue projecting from the optic disc
Persistent Primary hyperplastic vitreous:
U/L, premature child.

UVEA

Middle vascular layer of eyeball

Composed of iris, ciliary body & choroid
Stroma of all these are mesodermally derived
Consists of blood vessels, pigmented cells called
melanocytes and connec<ve <ssue.

IRIS

Developed from 2 layers

PMesoderm Anterior stroma
PNeuroectoderm-
iris pigment epithelium
sphincter and dilator muscles

pupillary membrane is formed by condensa<on of
mesenchyme situated in the anterior surface of the lens
2 layers of neuroectoderm forming the edge of op<c cup
extend to the posterior surface of pupillary membrane-
these structures fuse to become iris
Opening in the central part of iris becomes the pupil
Pupillary membrane begins to degenerate at about 8th
months of gesta<on

Applied Anatomy
Varying amount of atrophy of stromal vessels
(pupillary membrane) while peripheral
membrane remains well developed produce
the ne architecture of iris crypts
Pigmenta<on of stroma doesnt become
evident un<l afer birth, hence newborns
usually have blue iris

Polycoria, Ectopia, Corectopia, Aniridia

CILIARY BODY AND SUSPENSORY LIGAMENTS OF LENS

Mesenchyme at edge of op<c cup forms the-
Connec<ve <ssue of ciliary body,
Smooth muscle bres of ciliary muscle,
suspensory ligaments of lens

2 epithelial layers formed from neuroectoderm at the
edge of op<c cup
Pouter pigmented
PInner devoid of pigment

Ciliary body is situated between future iris epithelium and

peripheral re<na

Ciliary epithelium undergoes folding to form 70-75 ciliary
processes

 CHOROID

PMiddle vascular coat of eyeball. Begins to form at the

anterior region of the cup & proceeds posteriorly.
PFormed from mesenchyme surrounding the op<c vesicle
PHas 3 layers. The innermost Bruchs membrane is
derived from basement membrane of RPE ,
choriocapillaries layer, Elastic tissue and collagen
fibrils
PThe outer 2 layers are the - vascular and capillary
layers
PDuring 5th month melanocytes of neural crest origin may
be seen
PMelanocytes of neural crest origin are predisposed to
development of malignant melanoma

NUTSHELL:
Iris muscle-ectodermal in origin
Ciliary muscle is mesodermal in origin

CORNEA

Forma<on of cornea is induced by lens and op<c vesicle

forma<on
Epithelium derived from surface ectoderm
Bowmans membrane and Substan<a propria mesenchyme
Descemets membrane endothelial cells
Endothelium neural crest

Keratoconus
Is a condi<on when
the cornea assumes
a conical shape
secondary to stromal
thinning

 ANOMALIES
MICROCORNEA
Adult cornea<10mm in
horizontal diameter
Related to fetal arrest of
growth of cornea in 5th month
MEGALOCORNEA
Diameter 12mm or > at
birth&13mm or>afer 2 yrs
Due to failure of op<c cup to
grow & of its anterior <ps to
close

SCLERA
Outer tough brous coat of eyeball
Originates as the condensa<on of
mesenchyme outside the op<c cup 7th
week of gesta<on
First forms at the limbal region and
progresses peripherally un<l posterior pole is
reached 5th month
Primi<ve mesoderm dieren<ates into
collagen and elas<c bres of an adult sclera

Sclerocornea
There is sclera-like
clouding of cornea
Disorder of second
wave mesenchyme
migra<on
90% bilateral

ANTERIOR CHAMBER
It arises as a slit in the mesenchyme between the surface
ectoderm and developing Iris.
7th week angle of the anterior chamber is occupied by
mesenchymal cells of neural crest originTrabecular
meshwork
3rd monthSchlemms canal develops from small plexus of
venous canaliculi. The endothelial lining of Schlemm's canal is
mesodermal in origin.
5th monthVacuola<on of the endothelium around
Schlemm's canal occurs + individual cells are connected by
zonulae adherentes
Final dieren<a<on of deni<ve ltra<on apparatus occurs
shortly before birth.

Schlemm
canal

Scleral
spur

Trabecular
meshwork

POSTERIOR CHAMBER
Split in the mesenchyme posterior to the
developing iris and anterior to the developing
lens.
Anterior and Posterior Chamber
communicates when the pupillary membrane
disappears and pupil is formed
Aqueous humor lls these two chambers

RETINAL CIRCULATION
By 7th -8th month of gesta<on, re<nal vessels would
have extended nasally to ora serrata but only to
equator temporally
Vessels reach ora on temporal region only close to
term and even afer birth.
APPLIED ANATOMY:
Re5nopathy of prematurity excessive O2 in
premature infants vasoconstric<on obliterated
veins neovasculariza<on vascular area is non-
stretchable (detaches) / non-vascular area is
stretchable.

UVEAL CIRCULATION
Develops from vasoforma<ve paraxial mesoderm that
surrounds the op<c cup
6th week-
Common temporal ciliary artery branch of dorsal
ophthalmic artery runs along the temporal aspect of stalk &
cup
Common Nasal ciliary artery branches of ventral
ophthalmic artery runs along the nasal aspect of stalk & cup
These two vessels are the precursors of long posterior
ciliary artery
These anastomose with each other posteriorly & anteriorly
to form greater circle of iris.

3rd month

12 -15 short posterior ciliary arteries

develop from dorsal ophthalmic artery
Anterior ciliary artery
Develops from small tributaries from
muscular & lacrimal branch of
ophthalmic artery
Anastomose with branches of long
posterior ciliary artery

 Develop as folds of surface

ectoderm above and
below the developing
cornea.
Folds fuse at 3rd month
intrauterine life.
A closed space,
conjunc<val sac, exists in
front of cornea.
Separa<on of eyelids starts
by 5 month and completes
by the 7th month.

EYELIDS

 Connec.ve .ssue and tarsal plates Mesenchymal core

of the lids
Eyelashes epithelial buds from surface ectoderm
First appear in upper lid
Arranged in 2-3 rows

Glands of Zeis and Moll ciliary follicles

Tarsal/Meibomian glands develop as columns of
ectodermal cells from lid margins
Gland of Zeis and Moll
Mebomian gland
Orbicularis Oculi
Cornea

APPLIED ANATOMY- EYELID

cryptophthalmos Failure of separa<on of
eyelids
In cases of cryptophthalmos usually cornea is
absent

Ankyloblepharon adhesion of eyelids

Epicanthal Foldspalpebralis, tarsalis,
supraciliary and inversus

EXTRAOCULAR MUSCLES
From the mesenchyme in the region of
developing eyeball
four rec< muscles
superior and inferior oblique muscles
Ini<ally represented as a single mass of
mesenchyme
Later separates into dis<nct muscles, rst at
inser<ons and later at their origins

 Levator palpabrae superioris formed last

splihng from the mesenchyme that forms the
superior rectus
During development, muscles become
associated with III rd, IV th and VI th cranial
nerves
Orbicularis oculi muscle-

Mesenchyme of 2nd pharyngeal arch

Invades eyelids
Supplied by VIIth cranial nerve

APPLIED ANATOMY OF EOM

During congenital ptosis there is

paralysis of superior rectus muscle .

LACRIMAL GLAND
Form as series of epithelial
buds, which grow
superolaterally from superior
fornix of conjunc<va into the
underlying mesenchyme
Buds canalize- secretary units
mul<ple ducts
With the development of
Levator palpabrae superioris,
gland divides into-
orbital part
palpebral part

No tear produc<on un<l third

month afer birth

LACRIMAL SAC AND NASOLACRIMAL

DUCT
Develop as solid cord of ectodermal cells
between the nasal process and maxillary process
of the developing face

The cord later canalizes nasolacrimal duct
Superior end dilates to form lacrimal sac
Further cellular prolifera<on forms lacrimal ducts
which enters each eyelid

APPLIED ANATOMY

At junc<on of advancing cords there is a

membranous plate, and it is at this site that
block of NLD usually occurs in congenital NLD
block
Incomplete canaliza<on watering from
eyeinfec<on of the lacrimal duct and sac

ORBIT

Orbital bones mesenchyme that encircles the

op<c vesicle
Medial wall lateral nasal process
Lateral and inferior wall- maxillary process
Superior wall- mesenchymal capsule of
forebrain
Posteriorly from bones of base of skull
Orbital bones form in membrane, except those
forming the posterior part which form in
car<lage

 Axis of orbit-
At 1st month- 180 degrees laterally
At 2nd month - this angle begins to lessen
At 3rd month 72 degrees
Later stabilises at 45 degrees

Development of eyeball is at faster rate than

of orbit; at 6th intrauterine life anterior half of
eyeball projects beyond orbital opening

Primordial <ssues and its deriva<ves

Neuroectoderm
Surface ectoderm
Mesoderm

SUMMARY OF OCULAR
EMBRYOGENESIS
3rd week

4th week

1st month

Optic groove
appears

Optic pit
develops into
opticvesicle
Lens plate forms
Embryonic
Fissure develops

Lens pit then

Lens vesicle
form
Hyaloid vessels
develop

1 month

7th week

Closure of
embryonic
fissure
Proliferation of
neural retinal
cells
Appearance of
eyelid folds and
nasolacrimal duct

Formation of
embryonic
nucleus of the
lens
Sclera begins to
form
Migration of
waves of neural
crest

First wave:
formation of
corneal and
trabecular
endothelium
Second wave:
formation of
corneal stroma
Third wave:
formation of Iris
stroma

3rd month

4th month

Differentiation of precursors of
Rods and Cones
Anterior Chamber appears
Fetal nucleus starts to develop
Sclera condenses
Eyelid folds lengthen and fuse

Formation of Retinal
vasculature begins
Hyaloid vessels begin to regress
Formation of physiological
optic dsc and Lamina Cribosa
Canal of Schlemn appears
Bowmans membrane develop
Formation of major arterial
circle and spinchter muscle of
Iris

5th month

6th month

7th month

Photoreceptors
differentiate
Eyelid separation
begins

Differentiation of
dilator pupillae
muscle
Nasolacrimal
system becomes
patent
Cones
differentiate

Rods differentiate
Myelination of
optic nerve begins
Posterior
movement of
anterior chamber
angle
Retinal vessles
start reaching
nasal periphery

8th month

9th month

After birth

Completion of
anterior
chamber angle
formation
hyaloid
vessels
disappear

Retinal vessels
reach temporal
periphery
Pupillary
membrane
disappears

Macular region
of the retina
develops
further

Summary of various part of the eye ball.

Part

Derived from

Lens

Surface ectoderm

Re<na

Neuroectoderm (op<c cup)

Vitreous

Mesoderm

Choroid

Mesoderm (inltrated by neural crest cells?)

Ciliary body

Mesoderm

Ciliary muscles

Mesenchymal cells covering the developing ciliary body

(neural crest)

Iris

Mesoderm

Muscles of the iris

Neuroectoderm (from op<c cup)

Sclera

Mesoderm (inltrated by neural crest cells?)

Cornea

Surface epithelium by ectoderm, substan<a propria and inner

epithelium by neural crest

Conjunc<va

Surface ectoderm

Blood vessels

mesoderm

Op<c nerve

Neuroectoderm. Its covering (pia, arachnoid and dura) are

derived from mesoderm

Terima kasih