Foundation Volume 1, Chapter 25.

Anatomy and Embryology of the Optic Nerve

Chapter 25
Anatomy and Embryology of the Optic Nerve
JIE ZHANG, RICHARD M. RUBIN and NARSING A. RAO
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ANATOMY
HISTOLOGY
BLOOD SUPPLY
EMBRYOLOGY AND HISTOGENESIS
REFERENCES

ANATOMY
The optic nerve is a unique part of the central nervous system (CNS). It lacks
neuronal cell bodies and is isolated from the rest of the brain. The optic nerve
consists of unbranched axons of the retinal ganglion cells and the glial cells. The
number of axons can be considered a constant, whereas glia and myelin are present
in variable amounts relative to the axons and the surrounding microenvironment.
The human optic nerve is approximately 50 mm long from the back of the eye to the
optic chiasm and consists of four portions. The intraocular portion (optic nerve head)
is approximately 1 to 1.5 mm long and 1.5 mm in diameter and traverses the sclera.
The intraorbital portion, approximately 30 to 40 mm long and 3 to 4 mm in diameter,
has a sinuous course that allows for considerable excursion as the globe moves.
Approximately 8 to 15 mm behind the globe, the central retinal artery penetrates
and reaches the axia of the optic nerve (Fig. 1). The intracanalicular portion, which is
approximately 5 to 8 mm long, passes through the optic canal and is tightly fixed
within the canal. The intracranial portion is approximately 10 mm long and joins with
the contralateral nerve to form the optic chiasm. All of the CNS sheaths, including
the pia mater, arachnoid, and dura mater, surround the intraorbital portion of the
optic nerve.
Fig. 1. Anatomy of the optic nerve head and part of the
intraorbital portion of the optic nerve. The intraocular
part of the optic nerve consists of the nonmyelinated
axons and appears as a semitransparent, yellowish
segment (arrow). A portion of the intraorbital optic
nerve. The myelinated axons demonstrate a wax-white
color (**). The central retinal vessels penetrate into the
axia of the optic nerve. The dura mater is continuous
with the sclera (arrowhead).
Several important structures are situated close to the intracranial portion of the optic
nerve. The frontal lobe of the brain lies above each optic nerve. The anterior cerebral
and anterior communicating arteries separate the optic nerve from the olfactory
tract. Laterally, the ophthalmic artery arises from the internal carotid artery and is
located beneath the optic nerve near the optic canal. Because of the close anatomic
relationship that exists between the proximal optic nerve, the chiasm, and the
internal carotid artery and its branches, any space-occupying lesions that occur in
this area may compress the optic nerve or chiasm, resulting in vision loss and visual
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field defects. Also, diseases of the sphenoid and posterior ethmoid cells, which are
usually situated either inferiorly or inferomedially, may also affect the optic nerve
and chiasm.
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HISTOLOGY
OPTIC NERVE HEAD
The optic nerve head extends from the surface of the optic disc to the posterior
scleral surface,1 where the axons of the retinal ganglion cells form bundles that
emerge from the nerve fiber layer and turn to exit from the globe. For the purposes
of discussion, the optic nerve head is divided into three regions: (1) the surface
nerve fiber layer, (2) the prelaminar region, and (3) the lamina cribrosa region.2
1. The surface nerve fiber layer contains compact optic nerve fibers covered by a
layer of astrocytes (the inner limiting membrane of Elschnig) that separates
the nerve fiber layer from the vitreous. Its thickness is related to the size of
the physiologic cup. Eyes with a small cup have a thick membrane; eyes with a
large cup usually have a thinner membrane.
2. The prelaminar region consists of nonmyelinated axons, astrocytes, capillaries,
and surrounding connective tissues. The axons are arranged in bundles and
surrounded by astrocytes. At the lateral edges of the prelaminar region, the
axonal bundles are separated from the adjacent retina by glial tissue known as
the intermediary tissue of Kuhnt and from the choroid by a primarily
collagenous tissue known as the border tissue of Elschnig. A posterior
extension of glia from the intermediary tissue of Kuhnt, the so-called border
tissue of Jacoby, is located internal to the border tissue of Elschnig.1 The
prelaminar portions contain very little collagenous connective tissue other than
that which surrounds the central retinal vessels and capillaries of the disc.
3. The lamina cribrosa is a specialized, sieve-like region with many oval or round
openings through which pass the nerve fibers and the central retinal vessels.
This region consists of dense, compact collagenous sheets of scleral trabeculae
alternating with glial sheets. Elastic tissue is also found in this area.3,4 The
astrocytes that line the openings in the lamina cribrosa form a continuous glial
membrane that surrounds each nerve fiber bundle and separates the nerve
fiber bundles from the adjacent connective tissue (Fig. 2).

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Fig. 2. A. Histology of the optic nerve head.

Longitudinal section: (A) the surface nerve fiber
layer and the physiologic cup. (B) Prelaminar
region. (C) Lamina cribrosa region. The
nonmyelinated axons in the optic nerve head are
not stained by Luxol fast blue, whereas the
myelinated axons behind the lamina cribrosa are
stained. Luxol fast blue, 40. B. High
magnification demonstrates the transmission of
the nonmyelinated and myelinated axons, 400.

Immunohistochemical analysis reveals two subtypes of astrocytes, types 1A and 1B,

in the optic nerve head.5 Type 1A astrocytes, located at the edges of the cribriform
plates, form the glial limiting membrane that supports the axons. Type 1B astrocytes
form the glial columns, line the cribriform plates, and may interface between blood
vessels and other connective tissue surfaces.5 Both astrocyte subtypes, 1A and 1B,
are positive forglial fibrillary acidic protein (GFAP) and negative for A2B5, an
antibody that recognizes an epitope common to sialogangliosides and sulfatides in
the plasma membrane of neurons and neuroendocrine and glial cells.6,7 The major
difference between the two subtypes is that type 1A astrocytes are negative for both
HNK-1 and N-CAM (antibodies associated with the HNK-1 epitope and the neural cell
adhesion molecule, respectively), whereas type 1B cells are positive for both of
these antibodies.810 In contrast to the other portions of the optic nerve, there are
no oligodendrocytes in the optic nerve head.
INTRAORBITAL, INTRACANALICULAR, AND INTRACRANIAL PORTIONS OF
THE OPTIC NERVE
These three portions of the optic nerve are composed of myelinated axons;
neuroglial cells, including astrocytes, microglia, and oligodendrocytes; and
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fibrovascular septa, consisting of the blood vessels, fibroblasts, and pial

meningothelial cells. The axons are grouped into bundles by astrocyte columns and
vascular connective tissue septa. Within a group, axons are separated from each
other by myelin sheaths, interspaced with the cytoplasmic processes of glial cells.
Axons
The axons, also called nerve fibers, are the major component of the optic nerve. The
nonmyelinated axons of the retinal ganglion cells converge toward and turn sharply
on the optic disc. Once they penetrate the lamina cribrosa, the axons immediately
become myelinated (see Fig. 2). In cross-section using hematoxylin and eosin (H&E)
stain, the principal myelinated optic nerve fibers appear as small, faintly stained,
eosinophilic dots surrounded by relatively clear halos. These clear halos,
representing the myelin sheaths, are the result of lipid dissolution during processing.
Special stains can be used to enhance the appearance of axons (e.g., Bodian's
method and Luxol fast blue staining). Under electron microscopy, the nerve fibers
are identified as cytoplasm with mitochondria enveloped by multilaminar myelin
sheaths. The myelin sheaths of the optic nerve are formed by oligodendrocytes (Fig.
3). A distinct arrangement of axons is found in the optic nerve: the peripheral retinal
axons are located in the peripheral portion of the optic nerve, and the central area of
the nerve contains fibers from the posterior retina. Macular fibers form the
papillomacular bundle and enter the disc temporally; they remain temporal for a
short distance behind the eye, but as they proceed further posteriorly these fibers
become diffusely distributed. Nerve fibers arising in the nasal half of the retina cross
in the chiasm; axons arising in the temporal half are uncrossed.11 It is believed that
most optic nerve fibers carry afferent visual and pupillomotor impulses. A few fibers
project to the hypothalamus or superior colliculus, where they may provide afferent
information affecting the body's circadian rhythm or a rudimentary representation of
the visual space (blindsight), respectively.12,13 Efferent (centrifugal) fibers of the
optic nerve, presumed to be vasomotor in function, were identified in the human
optic nerve after enucleation of the globe. Silver staining of these axons showed
retrograde degeneration, whereas the remaining axons in the orbital portion of the
optic nerve showed little or no retrograde degeneration. In uninterrupted optic
nerve, efferent axons could not be differentiated from those of the afferent type.14
Fig. 3. Ultrastructure of the optic
nerve. (A) Axons are surrounded
by myelinated sheath. (B)
Oligodendritic cell. (M) Microglial
cell. 18,750. (Courtesy of Dr.
John R. Guy)

Glial Elements
As in the CNS, the glial elements of the optic nerve include astrocytes,
oligodendrocytes, and microglia. The astrocytes and oligodendrocytes are derived
from the neuroectoderm15; the origin of the micro-glia is controversial. Most studies
support their origin from mesoderm rather than ectoderm.16,17

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ASTROCYTES. All of the astrocytes in the optic nerve and optic nerve head appear
to be fibrous, with a large cell body and many long, coarse processes. Astrocytes line
the borders between axons and other tissues of the area, in particular the vitreous
interface, choroid, sclera, and capillaries. With H&E staining, the cell processes are
not demonstrable; their nuclei appear to be naked, and the cell bodies are likewise
arranged into longitudinal rows with interspersed astrocytes and oligodendrocytes.
Under electron microscopy, the astrocytes are characterized by rich processes,
extensively lobulated nuclei, numerous intermediate glial filaments, glycogen
granules and a wide type of granular endoplasmic reticulum.
In the optic nerve there are two subtypes of astrocytes, types 1 and 2, based on
differences in the intensity of staining with anti-GFAP and A2B5 antibodies. Type 1
astrocytes, which are GFAP positive and A2B5 negative, are located at the periphery
of the nerve and form the glial limitans.1820 Type 2 astrocytes are positive for GFAP
and A2B5. These are primarily located in the interior of the nerve and form
transversely oriented processes that end on blood vessels (Fig. 4). Functionally,
astrocytes provide a scaffolding that supports the axons and maintains a stable
biochemical environment around the nerve fibers. At the site of axonal loss,
astrocytes can form scar tissue, known as gliosis.
Fig. 4. Immunohistochemistry in longitudinal section of
the optic nerve. The processes and cytoplasm of the
astrocytes are stained positively by GFAP. The nuclei of
astrocytes are arrayed longitudinally. 660.

OLIGODENDROCYTES. Oligodendrocytes can make and maintain myelin sheaths of

the optic nerve axons, similar to the function of Schwann cells in the peripheral
nerves, but without forming a basement membrane around the myelin sheaths.21
Oligodendrocytes are normally absent in the retina and optic nerve head, appearing
posterior to the lamina cribrosa. Morphologically, they show small, round or oval
nuclei, a granular cytoplasm, and delicate branching processes that terminate in
loops. Oligodendrocytes are located in groups between the axons, usually near the
center of the axonal bundles, with their processes running parallel to the axons. In
contrast to the astrocytes, oligodendrocytes are devoid of footplates; they do not
exhibit any connection with connective tissue septa, and they lack the ability to
regenerate once injured.
When viewed by electron microscopy, oligodendrocytes appear moderately electron
dense compared with astrocytes. The nucleus is round or oval and is usually
eccentrically located, leaving a large mass of cytoplasm at one pole of the cell. The
nuclear content exhibits a slight clumping of chromatin that appears as a rim
beneath the nuclear envelope. The cytoplasm is rich in ribosomes, either free or
associated with the endoplasmic reticulum. The Golgi complex is well developed. The
oligodendrocytes have neither glycogen granules nor bundles of intermediate
filaments (see Fig. 3). When analyzed by immunohistochemical methods,
oligodendrocytes stain negative for GFAP but positive for galactocerebroside, myelin
basic protein, and neural cell marker HNK-1/N-CAM.5

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MICROGLIA. Microglia are the phagocytes of the CNS. In the normal optic nerve,
these cells are ordinarily present in small numbers, and most are found within
bundles of axons, with some situated adjacent to the glial septa and to blood
vessels.17 Normally, these cells are irregularly oval, containing small nuclei and
many long and slender branching processes. Under electron microscopy, microglial
cells have small, heterochromatic nuclei. The cytoplasm shows vacuoles, granular
endoplasmic reticulum arranged in long, narrow strands, and various inclusions,
including large dense bodies, lamellar bodies, myelin bodies, and other forms of
cellular debris (see Fig. 3).17 Immunohistochemical studies reveal that microglia in
the retina are positive for Griffonia simplicifolia B4-isolectin, CR3 complement
receptor, leukocyte common antigen (CD45), and antimacrophage marker CD68 (Fig.
5).22,23 These cells do not contain glial filaments.
Fig. 5. Immunohistochemistry in the longitudinal section
of the optic nerve. CD68-positive cells (red) are
scattered in the optic nerve and represent microglia.
660.

Microglia usually reside quietly in the optic nerve, but they can be easily activated by
trauma, inflammation, edema, or degenerative conditions. The activated microglia
become oval or rod-shaped, their small nuclei enlarge and become elongated, and
the complicated cytoplasmic processes are withdrawn. Activated cells can
phagocytize a variety of materials and can express major histocompatibility complex
class I and II molecules (see Fig. 5).22,23
Optic Nerve Sheaths and Their Spaces
The intraorbital portion of the optic nerve is enclosed by three sheaths that are
continuous with the meninges of the CNS: the dura mater, arachnoid, and pia mater
(Fig. 6). The outermost of these is the dura mater, a dense collagenous and elastic
tissue. Anteriorly, the dura mater frays and inserts into the sclera and rectus muscle
sheaths along with the ciliary arteries and nerves. Posteriorly, the dura mater divides
into two layers. One of these layers fuses with the periosteum of the bony canal and
with Zinn's annulus at the apex of the orbit; the remaining layer is tightly adherent
to the bone of the canal and the optic nerve. When the optic nerve passes the cranial
foramen of the canal, the dura mater becomes the periosteum of the sphenoid bone.
Therefore, even small lesions that occur within the canal or at its openings will
compress and damage the optic nerve.
Fig. 6. Cross-section of the optic nerve. (A) central
retinal artery; (V) central retinal vein; (S)
connective septa from the pia mater; (P) pia mater;
(An) arachnoid cell nests; (D) dura mater; (N) axon
bundles intermingled with glia cell nuclei.

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The arachnoid is composed of trabeculae of collagenous and elastic fibers lined by

meningothelia. It contains numerous vessels, along with some fibroblasts and
histiocytes. The meningothelia often proliferate in a concentric pattern and form
onion-like structures, with or without calcification, known as the psammoma bodies
or corpora arenacea, respectively.
The pia mater lies tightly on the surface of the nerve and consists of collagenous
fibers, elastic fibers, and a fused glial layer. The pia mater invests the nerve and
sends fibers into it to form the characteristic septa. The septa are separated from
the surrounding nervous tissue by the foot processes of the astrocytes, but they are
continuous with the collagenous adventitial sheaths of the central retinal artery and
vein within the optic nerve. The pia mater joins the sclera and choroid anteriorly;
posteriorly, it continues through the optic foramen to form the single sheath around
the intracranial portion of the optic nerve.
The potential space between the dura mater and the arachnoid, known as the
subdural space, does not communicate with the corresponding intracranial space and
has little clinical significance. The subarachnoid space, between the arachnoid and
the pia mater, is continuous with the corresponding intracranial space. It transmits
cerebrospinal fluid, which provides a pathway for the spread of blood, infectious
agents, and tumor cells between the eye and the CNS.
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BLOOD SUPPLY
OPTIC NERVE HEAD
The blood supply to the optic nerve head comes from an extensive network of
arterioles and capillaries originating from the short posterior ciliary arteries, the
central retinal vessels, the pia mater, and the choroid. The surface nerve fiber layer
is primarily supplied, in a centripetal pattern, by branches of the central retinal
artery arising in peripapillary retina. Direct choroidal contribution is not
demonstrated in this layer. Anteriorly, the capillaries in this region are continuous
with the retinal capillary bed atthe disc margin; posteriorly, they connect with the
capillary bed of the prelaminar region.2,2427 When the cilioretinal artery is present,
its precapillary branches may contribute to the temporal sector of this layer.2,26
The major blood supply to the prelaminar region is the short posterior ciliary
arteries. The central retinal artery does not directly contribute to this portion. In
fact, there is some controversy regarding the precise blood supply to this region. The
Zinn-Haller circle is an arterial anastomotic circle made up of the short posterior
ciliary arteries, but some investigators report that this circle is uncommon and
incomplete when it exists.2,28 Others point out the many anatomic variations of this
circle and its location approximately 200 to 300 mm posterior to the superchoroidal
space surrounding the optic nerve head.2527,29 The short posterior ciliary arteries
supply the prelaminar region, both through direct branches and via the Zinn-Haller
circle.
Another debate concerns whether the peripapillary choroidal vessels supply the optic
nerve head. Some reports have emphasized the contributions of the centripetal
branches from the peripapillary choroidal vessels to this region.2,28,30,31 Other
studies have shown that branches from the short posterior ciliary arteries, passing
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through the sclera rather than through the choroid, supply most of the optic nerve
head.25,27,32 However, 10% of the vessels entering the prelaminar region originate
from choroidal vessels.26 The capillaries in this region are complex, randomly
arranged, and continuous with the capillary bed of the surface nerve fiber layer and
laminar region. Because of the capillary network, the central retinal artery and the
short posterior ciliary artery can communicate and contribute to the prelaminar
region.26,33 Infrequently, the branches of cilioretinal arteries also supply this
region.26
The laminar region is entirely supplied by branches from the short posterior ciliary
arteries and the Zinn-Haller circle.2,26 The peripapillary choroid may contribute
occasional small arterioles.25 The capillaries in the laminar region form striated
layers following the pattern of the connective tissue septa of this region and are
continuous with the capillaries of the retrolaminar region.
The retrolaminar region is considered an integral part of the optic nerve head on the
basis of blood supply. The blood to this region comes mainly from the pial vessels on
the periphery of the optic nerve and branches arising from the short posterior ciliary
arteries.2,25 The central retinal artery also contributes centrifugal branches during its
intraneural course in the optic nerve.2 Hayreh2 reported contribution to this region
from the peripapillary choroid, but the same was not noted by Onda and
colleagues.25 This region also receives blood from the laminar region through a
continuous capillary network. The capillaries become sparse in this region in
comparison to the surface nerve fiber layer and the prelaminar and laminar
regions.3436 The blood supply to the optic nerve head is demonstrated in Figure 7.
Fig. 7. A. Arterial circulation of the anterior optic
nerve conceived as primarily centripetal and from a
single arterial source: the short posterior ciliary
arteries (SPCA) and their derivative choroidal
vessels (redrawn from Hayreh2). (CRA), central
retinal artery; (SNFL), superficial nerve fiber layer;
(Pre-LC), prelaminar region; (LC), lamina cribrosa;
(R-LC), retrolaminar cribrosa. B. Composite
illustration to scale of the various vascular
arrangements. Venous vessels and superficial
central retinal artery (CRA) plexus are not drawn in
all. Retrolamina: (1) pia mater as source of
transverse and longitudinal vessels. (2,2')
Recurrent short posterior ciliary artery (SPCA) to
retrolamina, and pial vessels to lamina cribrosa.
(3,3') Pial-derived longitudinal arterioles course to
and anastomose with laminar vasculature. (4)
Occasionally realized large pial arteriole courses
longitudinally through laminar tissue. (5) Intraneural branching of central retinal
artery, with anastomosis to laminar and retrolaminar systems. Lamina cribrosa: (6)
Transverse entry of scleral short posterior ciliary arteries that dominate laminar
vasculature and mingle with longitudinal microcirculation. Prelamina: (7) Branch of
short posterior ciliary artery courses through Elschnig tissue (E) at level choroid
(CH) and enters into nerve. (8) Occasionally choroidal vessel to prelamina; S
indicates sclera. Superficial nerve fiber layer (SNFL): (9) Choriocapillaris spur
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capillary anastomoses with other retinal and prelaminar vessels. (10) Both
epipapillary and peripapillary branches of central retinal artery anastomose with
prelaminar vessels. (Lieberman MF, Maumenee AE, Green WR: Histologic studies of
the vasculature of the anterior optic nerve. Am J Ophthalmol 82:405, 1976)
The venous drainage of the optic nerve head is mainly through centripetal tributaries
to the central retinal vein. Smaller venules also drain from the superficial nerve fiber
layer to the choroid (opticociliary veins).26
The arteries, veins, and capillaries in the optic nerve head and the nerve are similar
to the vessels of the CNS. The endothelia are nonfenestrated and have tight
junctions. Pericytes and their processes are found on the outside of the endothelia in
some capillaries. The blood vessels in the optic nerve head do not leak fluorescein or
other tracers. The capillary network of the optic nerve head is separate from that of
choroid. A vascular cuff is noted at the boundary of the peripapillary choroid and the
optic disc head, which also has nonfenestrated endothelia.27 Although the capillary
bed of the choroid similarly derives from the posterior ciliary arteries, it has a
fenestrated endothelium with few pericytes, and it leaks fluorescein.
OPTIC NERVE
It is generally agreed that the main blood supply to the intraorbital portion of the
optic nerve is directly or indirectly derived from the ophthalmic artery via the vessels
of the pia mater. Ophthalmic artery branches cross the dural sheath 10 to 12 mm
behind the eye to contribute to the pial system. Recurrent branches from the
posterior ciliary arteries and juxtapapillary choroid add to the anterior pial supply.
The centripetal branches from the central retinal artery may cosupply the intraorbital
optic nerve. The central retinal artery, also a branch of the ophthalmic artery, passes
directly through the subarachnoid space to enter the nerve, whereas the
accompanying vein has a variable course that is more oblique. The intracranial
portion of the optic nerve is supplied by the vessels derived from the internal carotid,
anterior cerebral, anterior communicating, and ophthalmic arteries. The pial
arterioles become capillaries as they pass through the pial septa into the axial
portion of the nerve. Capillaries in the retrolaminar optic nerve are continuous with
those of the laminar region but are decreased in number.3436
The pathway of the ophthalmic artery branches to the central retinal vessels through
the sheaths and into the nerve is of clinical importance. Neoplasms and
inflammatory processes originating in the eye or the optic nerve may follow their
course and gain access to the subarachnoid space and hence to the brain.
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EMBRYOLOGY AND HISTOGENESIS

OPTIC NERVE HEAD
The optic nerve head is formed late in the embryonic period as the optic stalk
encloses the hyaloid artery (the eighth week, 20-mm stage). At this stage, the
hyaloid artery is inside the hyaloid canal, which communicates with the primary
vitreous. Bergmeister's papilla consists of a cone-shaped mass of glial cells at the
mouth of the hyaloid canal (23- to 32-mm stage), where the hyaloid artery exits
from the disc. From the hyaloid artery, the vascular buds develop (the 13th week,
96-mm stage) within Bergmeister's papilla and through it into the nerve fiber layer
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of the retina. The glial cells form the sheaths of these vessels. Eventually, the
hyaloid artery disappears before birth, Bergmeister's papilla becomes atrophic, and
the physiologic cup of the optic disc develops at the 15th week of gestation.
OPTIC NERVE
Axons
The optic nerve develops from the embryonic optic stalk, which appears at the fourth
week and connects the optic vesicle to the forebrain (Table 1). As the stalk
lengthens, it becomes thinner and the lumen is progressively occupied by the axons
growing from the ganglion cells of the retina (the seventh week, 15-mm stage). In
the meantime, the embryonic cleft closes at the sixth week of gestation. At the
eighth week, axons fully occupy the stalk and reach the brain, and a rudimentary
optic chiasm is established. The mechanism by which the embryonic retinal ganglion
cell axons reach the optic disc remains unclear. Many factors, such as the paired box
containing the Pax2 gene,37 the axon guidance molecule netrin-1,38 and other cell
surface or extracellular matrix components39 may be involved in axon pathfinding
mechanisms. Expression errors of these molecules lead to optic nerve hypoplasia.
The axons of the optic nerve are surrounded by myelin sheaths. Myelinization begins
centrally, progresses in a centrifugal direction toward the eye, and terminates at the
level of the lamina cribrosa. The myelin sheath is produced by oligodendrocytes, and
myelinization is usually complete shortly after birth.

TABLE ONE. Development of the Optic Nerve 24,41,42

Week of
Gestation

Length
(mm)

Developing Events

2.56 mm

Short optic stalk

59 mm

Development of hyaloid vasculature

814 mm

Embryonic cleft closes

1318 mm

Growth of axons
Formation of optic nerve

1831 mm

Stalk fully occupied by axons

Axons of optic nerves reach the brain
Rudimentary optic chiasm established
Optic nerve vascularization starting to form
Optic nerve head starting to form

11

6573 mm

Vascular-connective septa invade the nerve

12

80 mm

Pia mater, arachnoid, and dura mater

distinguishable
Glial filaments appear

14

105 mm

Subarachnoid space appears

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117123 mm Physiologic cup starts to form

18

160 mm

Vascularization of the optic nerve completed

23

220 mm

Myelinization starts

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Optic Nerve Sheaths

The sheaths of the optic nerve begin to appear at the end of the seventh week. Thin,
elongated mesenchymal cells surround the optic nerve (10-mm stage) and become a
single compact layer by the 17-mm stage. The pia mater can be identified by the
ninth to tenth week of gestation (45- to 50-mm stage), followed by the dura mater
at the fifth month of gestation and the arachnoid sheath by the sixth and seventh
months of gestation. Both the pia mater and the arachnoid are derived from the
neural crest.
Glial Element
At the ninth week (45-mm stage), the glial cells in the optic nerve are oriented in
rows between the fascicles of axons. A peripheral layer of glial cells forms a glial
limitans made up of immature astrocytes with glial filaments under the thin
meningeal sheath. The glial limitans is separated from the pia mater by a complete
basement membrane. Astrocytes line the connective tissue septa and capillaries.
They are distributed among the axons at the 200-mm stage.
It has been suggested that optic nerve oligodendrocytes may originate from the
astrocytes that occupy the optic nerve before myelinization rather than exclusively
from glioblasts. The glial cells in the optic nerve and retina may differentiate into
astrocytes and oligodendrocytes.14,16,40,41
It is not clear whether microglia originate from mesoderm or ectoderm, although
most studies support a mesodermal origin.17 Under the electron microscope,
microglia are identified in the optic nerve at the eighth week of gestation. Most
microglia are found within bundles of axons, and there is no preferential distribution
in relation to blood vessels or to the pial surface at any stage of development. The
percentage of microglia present increases from 1.3% at 8 weeks to 2.7% at 18
weeks.14
Vasculature
The development of capillaries in the optic nerve and the CNS is similar. At the 11th
week (65- to 73-mm stage), vessels and connective tissue from the pia mater begin
to enter the proximal optic nerve and slowly enlarge the connective tissue septa
during the next few months.3 The capillaries within the optic nerve are separated
from the axons by a relatively complete astrocyte sheet and perivascular space. In
the 18th week (160-mm stage), vascularization of the optic nerve is completed, and
there may be anastomoses anteriorly by this stage with the arterial circle of ZinnHaller. The capillaries within the neural tissue are surrounded by astrocytes and by a
partially fused double basement membrane of both endothelial and glial cell origin.
The basement membrane along the astrocytic foot processes defines the limits of the
connective tissue septa along the neural tissue.41,42

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18. Raff MC: Glial cell diversification in the rat optic nerve. Science 243:1450, 1989
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36. Olver JM, Spalton DJ, McCartney ACE: Quantitative morphology of human
retrolaminar optic nerve vasculature. Invest Ophthalmol Vis Sci 35:3858, 1994
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