anatomical consideration of development of eye from embryonic stage. gives insight into future anatomical and pharmacological basis of drug development in disorders of eye.
2. Netra Uthpathi
It is gyanendriya adhisthanm meant for rupa grahanam.
Indriyas derived from atma.
Perticularly from vaikarik and taijas ahankar –all the 11
indriyas develop.(Su)
Netra indriya derived from Agni mahabhuta(Su)
Satwaguna+RajaGuna+Agnimahabhuta=Chaksyu
indriya(A.H)
According to A.S-Drusti is formed by essence of Kapha,
Raktha and and pancha mahabhutas.
Sukla mandalam- by the essence of kapha(Pittrija)
Krishna mandalam-By Raktha(Matrija)
Drustimandal- By both
3. Drusti is formed by the essence of Pancha mahabhutas
with Agni mahabhuta predominance.(Su)
Mamsa- Pruthwi mahabhuta
Raktha-Agni
Krishna mandala-Vayu
Sweta Mandala- Jala
Ashru Margam-Akasha mahabhuta.
According to Bhela - Aochak pitta takes part in
perception of vision, is of two types- Budhi vaisesik and
Chaksyu vaisesik.
4. INTRODUCTION
Ocular development is a continuous process and does
not proceed in a discrete stages.
For better understanding and description , the process of
ocular development is divided into 3 stages:
Embryogenesis
Organogenesis
Differentiation.
Embryogenesis-
Formation of three germinal layers of the developing
fetus-ectoderm, mesoderm and endoderm.
Organogenesis- Segregation and arrangement of the
primitive tissues to form the general pattern of the
organ,result in the development of the framework of eye.
Differentiation-The specific components of the eye are
developed
9. ORGANOGENESIS
Starts by 3rd week of gestation.
The first evidence of primitive eye formation
occurs during this period.
Neural Plate Procencephalon Optic
sulcus or optic pit(thickened and depressed
area on either side ).
As the optic sulcus deepens, the wall of the
procencephalon overlaying the sulcus bulges
outwards to form the optic vesicle.
The proximal part of optic vesicle
constricted and elongated to form optic stalk.
11. FORMATION OF THE LENS
Development of lens can be divided into two phases:
1.development of lens vesicle and 2. development of
lens fibers.
DEVELOPMENT OF LENS VESICLE
Optic vesicle grows laterally and comes in contact with
surface ectoderm.
Between 24th to 26th day, the surface ectoderm adjacent
to the optic vesicle thickens to form the lens placode.
The lens placode invaginates to form the lens
vesicle(between 32nd to 33rd day), which has a hallow
center.
After the lens vesicle separated from the surface
ectoderm, it is surrounded by basal lamina, which
becomes lens capsule.
Cuboidal cells line the anterior part of the lens vesicle
and the posterior portion of the lens vesicle is lined by
columnar cells that form the primary lens fiber.
12. Optic vesicles:
dilated end of
diverticulum-
invaginates & sinks
below the surface
ectoderm to form
double layered
optic cup.
Lens placode
lens vesicle.
By 22 days of
conception, optic
peduncles: a
bilateral
evagination of the
neuroectoderm of
the forebrain.
By 27 days, optic
vesicles (hollow
balls of
neuroectoderm
connected to the
brain- 3rd
ventricle- through
the hollow optic
stalk) reach
surface ectoderm
and induce
formation of lens
placode.
15. DEVELOPMENT OF LENS FIBER
The cells of anterior wall do
not devide and forms the lens
epithelium.
The posterior culumnar cells
do not devide but elongates to
form primary lens fibers and
obliterate the lumen of the
vesicle.
The primary lens fiber occupy
the central portion of the lens
forming the embryonic
nucleus.
This occurs between 5th to 8th
week of gestation.
16. Cont..
The primary lens fibers become attached to the apical surface of the
anterior lens epithelium.
Nuclei of the lens fibers move anteriorly within the cells to form a
line convex forward neuclear bow.
Secondary lens fibers additional lens fibers that are formed by
the division of the anterior epithelial cells of the equator.
New secondary lens fibers will be formed throughout life and lens
keeps enlarging.
At their anterior end(basal end) the fibers remain attached to the
basal lamina while their apical ends extend around the primary
fibers beneath the capsule.
The length of fibers not enough to reach from the anterior to the
posterior pole. At the two surfaces of the lens, therefore the ends of
the lens fibers meet one another successively to form lens
sutures.(2nd to 4th month)
The anterior becomes “Y” shaped and the posterior becomes
inverted “Y” shaped.
19. Cont..
The lens continues to grow through out the life
through the proliferation of secondary fibers
Due to the various stages of differentiation and
different optican dencities the lens nuclei
produce 4 zones
1. The embryonic nucleus-an optically clear
central area formed in embryonic life(during
1st to 3rd month) from primary lens fibers ,
which retains embryonic transparency.
2. The fetal nucleus-formed from secondary
fibers from the 3rd to 8th month of fetal life.
3. The infantile nucleus- formed from the last
week of fetal life through puberty.
4. The adult nucleus-formed after puberty in
adult life.
20. DEVELOPMENT OF CORNEA
Cornea: develops from surface ectoderm and mesoderm
At 5 to 6 weeks of gestation-the surface ectoderm separates
the lens vesicle to form the corneal epithelium.
7 weeks- mesenchyma cells derived from neural crest cells
migrate forward from around lens vesicle 3 waves.
The first wave of cells- trabecular endothelium
The 2nd wave of cells – corneal stroma
The 3rd wave of cells – migrate between the corneal
endothelim and lens to form- the iris stroma.
The final adult corneal epithelium attained by 37 weeks.
The corneal endothelium forms a two cell layer of cuboidal
cells.In 8th week the cells produce a basement membrane-
Decement’s membrane.
8 to 9 weeks- basal lamina of epithelim-produce Bowman’s
membrane.
SCLERA: derived from neural crest .Condensation of neural
crest tissue unitl12th week of development , sclera surrounds
the optiv nerve.
21. FORMATION OF THE OPTIC CUP AND
CHOROIDAL FISSURE
During 4th week of gestation, the optic vesicle is converted into a
double layered optic cup. This happens simultaneously while the
lens vesicle is being formed.
The margin of optic cup grows over the upper and lateral surface of
the lens to enclose it except in the inferior part of the lens.
The inferior invagination of the optic vesicle extends proximally to
involve the optic stalk. A deep groove appears on the ventral surface
of the growing optic cup and stalk, which is known as choroidal ,
embryonic or fetal fissure.
The embryonic fissure is essential for the growth and development
of the eye since it allows the exit of axons from ganglion cells
forming the optic nerve and the entry of the vascular system to
nourish the developing eye.
Vascular mesenchyme: grows inside the optic fissure taking
hyaloids artery with them. By 33 days.
Embryonic fissure closer around 33rd day.
• Optic canal: a narrow tube inside the optic stalk formed by 7th week
by narrowing & closure of optic fissure margins around the artery.
Failure coloboma
23. DEVELOPMENT OF RETINA
Retina consists of two layers developed from optic cup: pigmented
layer and neural layer and inter-retinal space (lumen) between them
that is continuous through the optic stalk with the 3rd ventricle.
The retina develops from the two parts of the optic cup
1. Outer layer of the optic cup- RPL(6th week)
2. Inner layer of optic cup- Neurosensory retina(6th wks-22nd wks )
6th weeek- outer wall of optic cup- become pigmented-posterior part
forms the RPL and anterior part continues forward in the cilliary
body and iris as their pigment epithelium.
Neural retina initially consists of
1. Outer neural epithelium- filled with 8 to 9 rows of nuclei
2. Inner marginal zone-devoid of nuclei called as the layer of His
Neural epithelium differentiated into two layers the inner and outer
neuroblastic layers and the transient layer of Chievitz, which
subsequently disapears.
The inner neuroblastic layer differentiates to form- ganglion cells,
Muller cells and amacrine cells(inner plexiform layers)
The outer neuroblstic layer differentiates to form- rods and cones,
bipolar cells and horizontal cells(outer plexiform layer)
24. DEVELOPMENT OF MACULAAND OPTIC NERVE
Development of macula delayed upto 8 months of gestation.
Thickening of ganglion cell layer temporal to the disc- 5th month.
6th month-center of macula-8 rows of nuclei.
Outer nuclear layer with immature cones , to the periphery
immature rods.
7th month-foveal depression starts.
4th month after birth-Both the ganglion cell layer and inner nuclear
layer retreat to the foveal slopes, leaving the cone nuclei bare in the
center of the depression.
Optic stalk develops into optic nerve.The optic stalk forms a
connection between the primary optic vesicle and the fore brain.
Optic fissure closure-5th week- optic stalk becomes a tube –receive
axons of ganglion cells and nerve fibes.
The epithelial cells of the inner wall of the stalk forms the glial
system of optic nerve.The outer basal lamina forms –glial lamina
cribrosa.
Latter with disappearance of the hyloid system, the pappila also
atrophies leaving a physiological cup.
The optic nerve sheath are derived from neural crest mesenchyme.
25. DEVELOPMENT OF UVEAL TRACT
Developed from the mesoderm and partly from the neuroectoderm.
Choroid -From mesenchyme surrounding the optic vesicle with
contribution of cranial neural crest cells.
1 to 2 month s- capillary channels , primitive choroid
3 months- chorio capillary forms from posterior to anterior.
6 to 7 months- Uveal melaniasation starts at disc and continues after
birth.(RPE melanization 5th week)
Bruch’s membrane is formed from outer layer of the optic cup.
Ciliary body – (3rd month) from both neuroectoderm and
mesoderm.
Two layered optic cup extends towards lens- pars caeca and pars optica,
the junction of these two is Orra serrata.
Ciliar muscle- 4th month- from mesoderm
Iris – 3rd month- forward extension of both wall of optic cup.
Vascular mesenchymae from neural crest forms-iris stroma.
The anterior part of tunica vasculosa lentis is replaced by the pupillary
membrane.
The spinchter and dilator muscles are neuroectodermal in origin.
Mature melanosomes are found in the iris around9 months of gestation.
27. VITVREOUS DEVELOPMENT
3 FOLD ORIGIN
Primary(primitive) -6 weeks (13 mm stage)-cellular. Partly
mesodermal and partly surface ectodermal. Later the hyloid system
of blood vessel invades through the embryonic fissure.
Secondary(Definitive)- 8 weeks(60-70mm)the neuroectoderm of
optic vesicle forms the secondary vitreous. (Vascular, hyloid
vessels, collagen fibrils,hyaluronic acid)
Arises between the primitive vitreous + retina and develops from
the retina.
Starts as a homogenous gel that increases in volume rapidly &
pushes the primitive vitreous anteriorly to behind the lens.
Hyalocytes derived from mesenchyme around hyaloids vessels.
Migrates into definitive vitreous.Later hyaloids vessels atrophy &
disappear leaving the acellular hyaloids canal.
Tertiary vitreous-> 12 weeks.The cilliary zonules are derived from
the neuroectoderm of cilliary region forms the tertiary vitreous.
Represented by vitreous base and cilliary zonules.
If the regression of primary vitreous fails –PHPV( Persistent
Hyperplastic Primary Vitreous)
28. DEVELOPMENT OF EYE LID , CONJUCTIVA
AND NASOLACRYMAL DUCT
1st sign of eye lid development- lid fold starts by 7th
week.
Eye lid from both surface ectoderm and mesenchyme.
Tarsus- from condensation of mesenchymal tissue.
Upper lid from lateral and medial frontonasal process of
mesenchymal condensation.
Lower lid from maxillary process.
Fusion of two lid around 9th week
Inward migration of ectodermal tissue gives rise to
meibomian glands, sweat glands and cillia.
Failure of fusion gives rise to coloboma of lids
Lids finally starts separating by 5th to 7th month.
Incomplete separation- Ankyloblepharon
Final maturation starts by 7th month of gestation.
30. Conjunctival sac formed in front of cornea while eyelids are fused.
Connective tissue + tarsal plates formed from mesenchyme core of
eyelids
Orbicularis oculi muscle formed from mesenchyme of second
pharyngeal arch which invades the eyelids & supplied by 7th cranial nerve.
Ciliary glands (moll & zeis) grow out from ciliary follicles
Tarsal glands (meibomian glands) develop as columns of ectodermal
cells from the lid margin
Lacrimal glands form as a series of ectodermal buds that grow
seperatly from the superior fornix at the conjunctiva into the underlying
mesenchyme
The buds later unite form secretory units & multiple ducts of the gland
After development of levator palpbrae superioris gland is divided into
orbital & palpebral
Tears are produced 3rd month after birth
Lacrimal sac & Nasolacrimal duct:
Solid cord at ectodermal cells between the lateral nasal process & maxillary
process of the face.
Cord is canalized to form the nasolacrimal duct. Superior end dilates to
form lacrimal sac.
Lacrimal duct formed by cellular proliferation.
31. SUMMARY OF OCULAR EMBROYOGENESIS
PERIOD AFTER
CONCEPTION
MAJOR MILESTONE
3 weeks Optic groove appears
4 weeks Optic pit develops into optic vesicle
Lens plate/placode forms
Embryonic fissure develops
1st month Lens vesicle forms
Hyaloid vessel develops
1 ½ month (6 weeks) Closer of embryonic fissure
Differentiation of RPE
Proliferation of neural retinal cells
Appearance of eye lid folds and nasolacrimal ducts
7th week Formation of embryonic nucleus of lens, sclera
bigins to form, Migration of waves of neural crest to
form corneal endothium, stroma and iris stroma.
3rd month Rod and cones precussor differentation , anterior
chamber appears, Fetal nucleus stats to develop
32. 4th month Hyaloid vessel begins to regress,
Formation of physiological optic
disc cup. Bowmans membrane
appears.
5th month Eye lid separation begins
6th month Differentiation of dilator pupillae
muscle, cones differentiate, Naso
lacrimal system becomes patent.
7th month Rods differentiate,
Myelination of optic nerve, retinal
vessels starts reaching nasal
periphery
8th month Hyaloid vessel dissapears
9th month Pupillary membrane dissapears
After birth Macular region develops further.
33. Part Derived from
Lens Surface ectoderm
Retina Neuroectoderm (optic cup)
Vitreous Mesoderm- mesenchyme
Choroid Mesoderm (infiltrated by neural crest cells)
Ciliary body Mesoderm
Ciliary muscles Mesenchymal cells covering the developing ciliary body (neural
crest)
Iris Mesoderm- mesenchyme
Muscles of the iris Neuroectoderm (from optic cup)
Sclera Mesoderm (infiltrated by neural crest cells?)
Cornea Surface epithelium by ectoderm, substantia propria and inner
epithelium by neural crest
Conjunctiva Surface ectoderm
Blood vessels mesoderm- mesenchyme
Optic nerve Neuroectoderm. Its covering (pia, arachnoid and dura) are
derived from mesoderm
SUMMERY OF DEVELOPMENT OF EYE BALL
34. DEVLOPMENTAL OCULAR ANOMALIES
Anophthalmia- congenital absence of eye- optic pit does not
develop properly
Microphthalmia
Congenital cystic eye- arrest of inavination of optic vesicle to form
optic cup.
Cyclopia – total fusion of the optic vesicles.
Synophthalmia- partial fusion of the optic vesicle.
Colobomas : coloboma refers to any notch, gap or fissure.
Coloboma occurilure of closer of embryonic fissure. May be iris,
choroid ciliary body, retina, and optic nerve.
Lens abnormalities:
Congenital Aphakia- lens failed to develop.
Microspherophakia- bilateral , small and spheric lens.
Anterior lenticonus, posterior lenticonus and developmental
cataract.
Persistent pupilary membrane and Metendorf’s dot – due to failure
of regression of Hyloid system of vessels. ( third month).
35. SCLERAL ANOMALIES- Blue sclera- blue clera, brittle bone and
deafness triad in osteogenesis imperfecta
CORNEAL ANOMALIES
SCLEROCORNEA- limbus is clinically indiscnict and the opque
scleral tissue extend to the cornea.
Microcornea- <11mm
Megalocornea- >14mm
Posterior keratoconus
Posterior embryotoxon- white line on the cornea with strands of iris
from peripheral iris to this white line.
Axenfeld - Rieger syndrome
Peters’ anomaly– central corneal opacity that persists fron birth- due
to failure or incomplete separation of lens vesicle from the surface
ectoderm.
Anomalies of Iris: corectopia, Aniridia
Vitreous anomalies-PHPV
36. Cont..
OPTIC NERVE Anomalies: Optic nerve apasia,
optic nerve hypoplasia,
Morning Glory Disc Anomaly-
Lid Anomaleis- Cryptophthalmos –sheet of the
skin covers the eye- due to failure of separation
of the lids during 5th months of gestation.
Eye lid colobomas
Congenital ptosis
Ankyloblepharon
RETINAL – Retinal dysplasia.
46. REFERENCES
Text book of ophthalmology- Agarwal and co-Jaypee
publication
Chapter 53.
Ocular Developmental Anomalies
SCOTT E. OLITSKY and LEONARD B. NELSON.
Comprehenive ophthalmology-A K Khurana-5th
edition.
Post graduate ophthalmology- Choudhuri and M.
Vanitha
Modern ophthalmology- L.C.Dutta.
Parsons’ Diseases of Eye-21st edition.
Shalakaya Tantra –Dingari Laxman Chari-first
edition-2005.
Editor's Notes
After fertilization-rapid mitotic division-morula (solid ball of cells)-cells rearrange and organize around a fluid filled cavity (blastocyst)-cells divide and accumulate one pity to form ole(embryoblast)- differentiate into two layer-Central epiblast and outer hypoblast-devide the central cavity to form the amniontic cavity and the yolk sac.Epiblast cell invaginates to form the mesoderm layer.