Chapter 186 – Anatomy and Physiology
ALFREDO A. SADUN
• The optic nerve, being a portion of the central nervous system, is really a tract and not a (peripheral) nerve. However, as a convention, the 1.2 million axons that derive from the retinal ganglion cells carry the name the optic nerve until they partially decussate at the optic chiasm.
Until recently, anatomical tracing techniques, quite useful in animals, could not be applied to delineate the fiber projections in humans. Hence, much of what is taught concerning the visual projections in humans derives from experimental animal studies. Because a great deal of interspecies variation exists in anatomy, some scholars rely largely on the original dissection studies performed on humans.
The optic nerves are obvious—Aristotle described them as joining at the optic chiasm, now so called because it resembles the Greek letter ? (chi). Galen of Pergamon, in about AD 150, gave a more detailed description of the optic nerves as sensory in nature but incorrectly as hollow and continuous with the ventricular system. Little progress in the understanding of the visual pathways occurred between Galen and Gratiolet, 1700 years later. Using orangewood sticks (soft) for blunt dissection, Gratiolet was able to tease, as much as trace, the retinofugal projection to the pretectum via the brachium of the superior colliculus and to confirm the main pathway from the optic chiasm to the lateral geniculate nucleus and hence to the cerebral cortex.
The optic nerve carries about 1.2 million axons that derive from the retinal ganglion cells and project to the eight primary visual nuclei ( Fig. 186-1 ).    However, only the anterior part of this heavily myelinated tract is termed the optic nerve. The optic chiasm consists of the partial decussation; the optic tract is the posterior continuation of the same fiber tract to its termination.
Hence, the optic nerve is about 50?mm long and extends from the eye to the optic chiasm. It is often described as consisting of four portions (see Fig. 186-2 ):
Figure 186-1 Retinal projections to the eight primary nuclei, showing distribution of higher order visual processing.
• Intraocular portion (the optic disc, 1?mm in anterior-posterior length)
• Intraorbital portion (about 25?mm long)
• Intracanalicular portion within the optic canal (about 9?mm long)
• Intracranial portion (about 16?mm long)
Three anatomical zones occur within the 1?mm long intraocular optic nerve (optic disc):
• Anteriorly, the retinal or prelaminar zone
• Centrally, the choroidal or laminar zone
• Posteriorly, the scleral or retrolaminar zone
Figure 186-2 The four portions of the optic nerve. The lengths are given.
Each zone contains different structures and elements of neuroectoderm and mesoderm. 
A retinal ganglion cell axon, once myelinated, is termed an optic nerve fiber. This terminology may cause confusion because the retinal nerve fibers consist of retinal ganglion axons that are unmyelinated and have not yet reached the optic disc. A topographical separation of fibers begins in the retina, continues in the optic nerve, and then becomes less precise near the optic chiasm.
The axons represent the anatomical substrate of the neural connection. Their membrane cable properties permit a regenerative signal to be transferred from the retina to the primary visual nuclei. This signal travels fastest in the axons of largest caliber and in those with the most myelin. Conduction velocities in large, myelinated fibers (about 20?m/sec) are much faster than the velocities in small, unmyelinated fibers (about 1?m/sec) in the retina.
This optic nerve–mediated signal is coded spatially (the axons are retinotopically distributed in the brain) and probably temporally as well (axonal firing frequency carries information).
In addition to the neural signals, axons permit the transfer of intracellular chemicals and organelles, such as mitochondria, from the neuron soma to the distal terminal and vice versa. Orthograde (proceeds from eye to brain) axoplasmic transport has a slow component that progresses at 0.5–3.0?mm/day and a rapid component that moves at 200–1000?mm/day.  Retrograde (brain to eye) axonal transport also occurs at an intermediate rate.
It has been suggested that, in humans, at least two classes of retinal ganglion cells exist. About 90% of the retinal ganglion cells are relatively small, concentrated in the macula, and contribute axons of small caliber that project to the parvocellular layers of the dorsal lateral geniculate nucleus (the so-called P-cell system). P cells have color-opponent physiology and are thought to subserve high-contrast, high-spatial-frequency resolution. In contradistinction, M cells are larger cells that contain large, fast-conducting axons and make up about 5–10% of the retinal ganglion cells. The M cells may be involved primarily with noncolor information of high temporal and low spatial frequency. 
Oligodendrocytes are specialized glia that provide membranes for axonal myelination. Such myelination begins centrally during development and stops at the lamina cribrosa of the optic disc at birth. However, oligodendrocytes may extend anomalously anterior to the lamina to myelinate the peripapillary retinal nerve fiber layer (optic disc medullation) in about 1% of the general population.
Microglia and macrophages are cells that derive from the immune system and can move readily into the central nervous system from the vascular beds. These immunocompetent cells probably play a far greater role than simple protection of the optic nerve from infection. For example, the apoptosis (programmed death) of retinal ganglion cells, which occurs during development and in various diseases, is probably modulated by these glial cells.
Astrocytes have extensive neurofibrillary processes that spread among the nerve fibers. These specialized glial cells line the borders between axons and other tissues, such as capillaries. They form part of the blood-brain barrier and play a role in the nutritional and structural support of axons. Intercellular junctions between cells couple chains of astrocytes electrically and biochemically.  When axons are lost because of optic atrophy, astrocytes move and proliferate to fill all the empty spaces.
FOUR PORTIONS OF THE OPTIC NERVE
The optic nerve head is 1?mm deep in the anteroposterior direction and 1.5?mm (horizontally) by 1.8?mm (vertically) in diameter at the level of the retina. The retinal ganglion axons make an orthogonal turn from the nerve fiber layer and pass through one of 200–300 holes that perforate the lamina cribrosa, the collagenous support of the optic disc. These axons must pass from an area of higher tissue pressure (intraocular compartment) to a zone of lower pressure (retrobulbar space). The collagen plates and specialized glial tissue maintain the pressure differential. The arterial supply shifts from the central retinal artery to branches of the ophthalmic artery. The axons become myelinated immediately at the posterior end of the optic nerve head.
Intraorbital Optic Nerve
This portion of the nerve (25?mm) exceeds the anteroposterior distance from the globe to the optic foramen by at least 8?mm. This redundancy of the sinuous optic nerve protects it and the eye during eye movements or in the event of up to 9?mm of proptosis.
The optic nerve diameter increases from 3?mm just behind the globe to about 4?mm at the orbital apex. Throughout its orbital course, the nerve is surrounded by dura, arachnoid, and pia mater ( Fig. 186-3 ). The outermost sheath is the dura and is composed of
Figure 186-3 Anterior optic nerve. The sheath and the vascular supply to the intraocular and intraorbital portions are shown.
Figure 186-4 Retrobulbar optic nerve. This cross section is approximately 5?mm behind the globe and is a 1?µm Epon-embedded section stained with para-phenylenediamine. The axon fascicles (about 400–600 per nerve) each carry approximately 2000 axons. The fascicles are separated by connective tissue septa. In the lower left, the central artery and vein can be seen. On the right, the pial surface is visible.
dense collagen. The arachnoid, which lies under the dura, is more cellular and less collagenous. Delicate arachnoidal trabeculae connect this membrane with the dura and underlying pia. The pia is the most delicate and the most vascular of the sheaths that cover the optic nerve. The subarachnoid space is continuous with the intracranial subarachnoid space and carries cerebrospinal fluid.
The optic nerve substance consists of 400–600 fascicles, each of which contain about 2000 fibers ( Fig. 186-4 ). The fascicles are separated by connective tissue septa through which run the smaller blood vessels. The axons are myelinated heavily ( Fig. 186-5 ) by oligodendrocytes.
Intracanalicular Optic Nerve
The optic nerve’s intracanalicular portion begins as it enters the optic canal through an opening in the lesser wing of the sphenoid bone at the apex of the orbit known as the optic foramen ( Fig. 186-2 ). The orbital canal opening is elliptic, with its widest diameter oriented vertically. The intracranial opening of the optic canal is also elliptic but with the horizontal width greater
Figure 186-5 Axon in the retrobulbar optic nerve. This is an ultrastructural high-magnification view approximately 5?mm behind the globe and is 400× the magnification of Figure 186-4 . Note the heavily myelinated axons of various sizes. The smaller axons are 0.6–0.9?µm in diameter and are probably of retinal ganglion cells of the P-cell system. The larger axons are 1–2?µm in diameter and may be part of the M-cell system. Mitochondria and cellular debris can be seen intra-axonally.
than the height. The medial canal wall is the thinnest and most likely to fracture.
Unlike the intraorbital optic nerve, the intracanalicular optic nerve does not move freely and is fixed tightly within the optic canal. Thus, small lesions that arise within the optic canal may compress and significantly damage the optic nerve while still relatively small and not radiologically visible.
Intracranial Optic Nerve
Once past the hard fold of dura above the intracranial opening of the canal, the intracranial optic nerve runs for 12–16?mm to reach the optic chiasm. The intracranial optic nerve is now about 4.5?mm in average diameter.
Above each nerve lie the gyri recti of the frontal lobes of the brain. On the lateral side of the optic nerve may lie the internal carotid artery, or alternatively the anterior cerebral and middle cerebral arteries may lie immediately adjacent. The ophthalmic artery arises from the carotid and lies to the lateral side and below the nerve within its dural sheath. The proximity of the cavernous
sinus makes it possible for tumors to produce cranial nerve palsies in combination with an optic neuropathy.
CIRCULATION OF THE OPTIC NERVE
The ophthalmic artery derives from the top of the internal carotid artery siphon, where it joins up with and occupies an inferior position to the nerve in the optic canal. In the canal and orbit, the artery gives off several branches that feed the pial circulation. At 8–12?mm behind the globe, the ophthalmic artery passes through the nerve sheath and into the nerve, where it runs along the central aspect of the nerve up to the optic disc; here, it is renamed as the central retinal artery ( Fig. 186-3 ); this artery does not contribute directly to the circulation of the optic nerve head. Instead, blood flow to the optic nerve head derives from the circle of Zinn-Haller, which receives three major sources of blood.  
• Choroidal vessels
• Four or five short posterior ciliary arteries
• Small contribution from the pial arterial network
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