Ординатура / Офтальмология / Английские материалы / The Retina and its Disorders_Besharse, Bok_2011

and tertiary neurons in response to light stimulation. In general, ON cone bipolar cells are excited by light that is brighter than its surround, whereas OFF cone bipolar cells are excited by light that is dimmer. This segregation of visual input is maintained in parallel signaling pathways to ON and OFF ganglion cells (see Figure 1).

Lateral Communication Networks

Signal transfer through the retinal layers, particularly for the rod system, depends on lateral communication between retinal cells. There are several cell types and neural connections within retinal layers that mediate lateral transfer of signal. The major cell types include amacrine and horizontal cells but lateral transfer is also accomplished by a class of low-resistance electrical gap junctions.

Gap Junctions

Low-resistance electrical gap junctions are ubiquitous in the mammalian retina. They enable the intercellular, bidirectional transport of ions, metabolites, and secondorder messengers. These gap junctions are mediated by connexins of which several different types have been reported in the mammalian retina. The most abundant of these is neuronal Connexin36. Connexin36 is associated with processes in the outer and inner plexiform layers, consistent with expression in multiple cell types. In the outer plexiform layer, cone photoreceptors communicate laterally via Connexin36-mediated gap junctions between cone pedicles (see Figure 1). The gap junctions also permit signal transfer between cone pedicles and rod spherules. In the inner plexiform layer, the expression of Connexin36 co-localizes with the dendritic processes of AII-type amacrine cells. The latter gap junction mediates transfer of signal from AII amacrine cells to ON cone bipolar cells, a signaling pathway that is crucial for rod signals to infiltrate the cone postreceptoral signaling pathway. In addition, the gap junctions in the outer plexiform layer (between cone pedicles and rod spherules) allow rod signals to infiltrate the cone signaling pathway very early in visual processing. These pathways are described later in more detail.

Horizontal Cells

Horizontal cells are second-order, mainly inhibitory, neurons located in the outer plexiform layer. While these cells make synaptic connections with photoreceptors, they are also extensively coupled by either Connexin50 or Connexin57 gap junctions. Morphologically, three types of horizontal cells have been identified in the primate and human retina, referred to as HI, HII, and HIII. The HI-type horizontal cells have small dendritic fields (75–150 mm), but with long axons (300 mm) ending in a broad dendritic tree. HIII horizontal cells are similar to the HI horizontal cell

but have larger dendritic trees at all retinal locations. In addition, HIII cells contact many more cones than HI. HII horizontal cells are more spidery and intricate in dendritic field characteristics than either of the other types. The three types of horizontal cells in the human retina demonstrate evidence of color-specific coding. HI horizontal cells contact primarily with greenand red-sensitive cones, with a smaller number of contacts with blue-sensitive cones. HII horizontal cells contact blue-sensitive cones primarily, and HIII horizontal cells contact only greenand red-sensitive cones.

Most, if not all, of the input to horizontal cells is derived from the response of cone photoreceptors to light and, depending on the type of horizontal cell, can make contact with many cones over broad retinal areas. In addition, because horizontal cells are extensively coupled via electrical gap junctions, their receptive fields can be much larger than their dendritic spreads. The connection to rod photoreceptors has traditionally been thought to occur at the axon terminal process, implying that signal transfer from cones to rods is unidirectional. However, rod inputs have been recorded in horizontal cell somata in the cat retina, presumed to be delivered via cone-rod gap junctions or direct dendritic connections. Like cone OFF bipolar cells, horizontal cells express iGluRs at their dendrites and are hyperpolarized in response to light.

In the primate retina, the transmitter release from cones that drives horizontal cells and bipolar cells is also regulated by feedback from horizontal cells. This feedback loop provides a mechanism for the inhibition of signals from adjacent cone photoreceptors. The precise mechanism by which horizontal cells produce this lateral inhibition is not well understood but may occur as a result of the modulated release of the inhibitory transmitter g-aminobutyric acid (GABA) at the synaptic terminal of cones or via the modulation of the Ca2þ channels that regulate the release of glutamate. Regardless of the precise mechanism of lateral inhibition, the lateral interconnections provided by horizontal cells contribute to the formation of the antagonistic surrounds of bipolar cell receptive fields. The antagonistic center-surround interaction is thought to enhance the detection of edges but have also been implicated in the processing of color information where the center-surround configuration modulates antagonistic (or opponent) color information, and in illusory surface filling effects. In addition, the observation of rod and cone inputs at horizontal cell somata provides a mechanism for integrating light signals over broad retinal areas to ensure optimal retinal sensitivity over the entire intensity range.

Amacrine Cells

There are up to 30 types of amacrine cells located in the inner retina of the mammalian retina that have been

distinguished on the basis of morphological characteristics, physiological properties, and pharmacological criteria. While cells upstream from amacrine cells generate graded potentials in response to stimulation by light, the amacrine cell is the first site in the retina where action potentials are generated. Amacrine cells receive their input from bipolar cells, mediated by iGluRs at the synaptic terminals, and from ganglion cells and other types of amacrine cells. The main job of the amacrine cells is to provide a mechanism for transfer of signals from bipolar cells within and between sublamina of the inner plexiform layer, and with ganglion cells. However, amacrine cells, like horizontal cells, provide a mechanism for lateral signal communication between retinal cells, including providing a feedback loop to bipolar cells. They are assumed to play an important role in modulating activity in the antagonistic surrounds of ganglion cell receptive fields that shape higher visual functions, such as object segregation and spatio-temporal adaptation. The feedback from amacrine cells has also been implicated in switching the site of light adaptation between receptor and postreceptoral sites.

The extent of lateral transfer depends on the morphology of the amacrine cell. Wide-field amacrine cells transmit lateral information across a broad expanse of the inner plexiform layer and are present in many species, including the mouse, rat, cat, rabbit, salamander, and monkey. Small-field amacrine cells mediate local interactions between different sublaminae of the IPL. The best characterized of these is the AII amacrine cell which plays an important role in mediating signal transfer through the rod-mediated neural circuitry. Unlike cone bipolar cells, rod ON polar cells do not make direct contact with ON ganglion cells. Rather rod signals are transmitted to ON ganglion cells by AII electrical coupling (gap junctions) with ON cone bipolar cells and by synaptic connections with OFF-cone bipolar cells (see below). Another amacrine cell type, the A17 amacrine cell, has also been implicated in the rod-signaling pathway of the mammalian retina. Up to 11 other small-field amacrine cells have been identified in the cat, rabbit, and mouse, but their precise function is not well understood.

Ganglion Cells

Signals carried through the retinal layers converge on ganglion cells, the latter responsible for carrying information to higher-order visual centers. Up to 25 different types of ganglion cells have been identified in the mammalian retina, dependent on species. These retinal ganglion cells are broadly grouped into classes based on morphological characteristics and physiological properties. In the primate retina, for example, there are at least 18 different types of retinal ganglion cells that are classified morphologically into Pa (parasol), Pb (midget), and Pg types, and physiologically into two major types:

parasol or magnocellular (M), and midget or parvocellular (P) cells. The parvocellular cells project exclusively to the parvocellular layers of the lateral geniculate nucleus (LGN) and play a key role in central acuity. Parasol ganglion cells are motion-sensitive cells and primarily project to the magnocellular layers of the LGN. Intrinsically photosensitive retinal ganglion cells (ipRGCs) containing melanopsin as the photosenstitive pigment have also been described recently. These neurons, which receive input from both rod and cone photoreceptors, have been implicated in nonimage-forming responses to environmental light such as the pupillary light reflex and circadian entrainment.

Multiple Rod Signaling Pathways

Cone photoreceptors synapse directly with both ON and OFF bipolar cells, which then transmit signals in parallel pathways to ON and OFF ganglion cells, respectively (Figure 1). In contrast, rod photoreceptors, which synapse with rod ON bipolar cells, do not make direct contact with ganglion cells, but rather transmit their signals to these cells through several alternate pathways. Consider first the evidence for multiple rod pathways. The alternative signaling pathways are described later and shown in

Figure 2.

It is generally accepted that rod-mediated vision, like cone vision, involves multiple signaling pathways. The evidence in support of this hypothesis derives from early psychophysical experiments in humans in which critical fusion frequency (CFF; the intensity at which flicker can just be detected) was measured under conditions mediated by rods. These experiments revealed two distinct branches in the function that relates CFF and stimulus intensity. In the lower branch, over dim flash intensities, the CFF was no better than 15 Hz, and remained at this level over a broad range of stimulus intensities. However, at higher intensities, covering mesopic light levels, CFFs increased rapidly and could be as high as 28 Hz. The doublebranched CFF versus intensity response function implied the existence of at least two signaling pathways mediating rod function in the mammalian retina. This hypothesis was supported by the observation that patients with achromatopsia, a retinal abnormality in which cone function is absent, also display the same response properties.

Additional support for at least dual rod signaling pathways comes from psychophysical measurements of rod flicker perception in humans. These experiments demonstrated that for 15 Hz flickering stimuli (the optimal stimulus presentation frequency for demonstrating the interaction), there is an intensity region, well above flicker detection threshold, where the perception of flicker is minimized or nulled. The perceptual nulling of flicker has been assumed to result from the mutual cancellation of signals originating from at least two signaling pathways

IPL

GJ

GCL

GCL

GCL

having different speeds of signal transmission. The hypothesis argues that when signals are in phase, despite different speeds of transmission, they are mutually additive but, when out of phase, produce destructive interference, which contributes to the inhibition of signal strength and the flicker nulling perception. This mutual cancellation has also been demonstrated with the electroretinogram (ERG), which is a noninvasive measure of the massed response of the retina to light. It is assumed only to reflect activity of outer and middle retinal cells. As in the perceptual experiments described above, supportive evidence derives from a unique feature of the function that relates ERG signal amplitude and stimulus. A local response minimum is observed at an intensity that is well above ERG flicker detection threshold but still within the scotopic range of intensities and occurs at the same intensity where the perception of flicker in humans is also minimized.

Much of the electrophysiological evidence in support of the existence of multiple signaling pathways comes from experiments in which single unit extracellular recordings are made from ganglion cells in the mouse and rabbit retina. Using pharmacological agents to disrupt different cellular connections in the retinal circuitry, combined with animal models with known genetic defects affecting these connections, electrophysiological support for multiple rod

pathways has come from what signals remain detectable at the ganglion cell level. On the basis of these types of experiments, rod photoreceptor signals are presumed to be transmitted to ganglion cells via three alternate pathways.

The anatomical substrates mediating rod postreceptoral signaling in the retina seem to be well established and are assumed to be conserved across mammalian species. They are illustrated in Figure 2. In the primary rod pathway (left panel), rod photoreceptors synapse with rod ON bipolar cells, via sign-inverting glutamatergic synapses. The output from the rod ON bipolar cell is then transmitted to AII amacrine cells in the inner plexiform layer via sign-conserving glutamatergic synapses. Signals from the AII amacrine cells then converge onto the cone pathway by exciting ON cone bipolar cells via electrical gap junctions and inhibit cone OFF bipolar cells via sign-inverting glycinergic synapses (see Figure 2 for color coding).

Rod signaling through the secondary rod pathway (middle panel) converges onto the cone circuitry at an even earlier stage. The secondary rod pathway is mediated through rod-cone gap junctions that exist between rod spherules and cone pedicles located in the outer plexiform layer. Through the rod-cone gap junction, rod

photoreceptors can transmit signals directly to both ON and OFF cone bipolar cells and to ON and OFF ganglion cells. The circuitry for the primary and secondary rod pathways has been shown to exist in the cat, rabbit, primate, and more recently in the mouse.

A third pathway for rod signal transmission (right panel), in which rod photoreceptors bypass the rod ON bipolar cell and directly excite cone OFF bipolar cells, has also been hypothesized and supported by anatomical and physiological data. This alternative pathway has been demonstrated to exist using electrophysiological methods. In these experiments, a ganglion cell signal continues to be observed in animals without cones (thereby eliminating the rod–cone gap junction of the secondary pathway) and in which all signal transmission through the primary rod pathway is blocked with pharmacological agents.

Thus, the retinal circuitry comprising the rod system offers multiple signaling routes for carrying information from rod photoreceptors to inner retinal ganglion cells. While these signaling pathways provide the rod system with multiple opportunities for system redundancy, they also subserve specialized functions related to scotopic vision. It has been suggested that signal transfer from the primary to secondary rod signaling pathway affords the rod system the capability of enhanced temporal resolution at the expense of light sensitivity. However, further work is needed to better understand the precise role of each of the rod signaling pathways in the processing of visual information.

Concluding Statements

A major step in forming our perceptions of the visual world is accomplished in the retina, where information from rod and cone photoreceptors is filtered, processed, and channeled through multiple parallel signaling pathways. In addition to the different spectral sensitivities of rod and cone photoreceptors and the intensity range over which they operate, the different types of bipolar cells, amacrine cells, and horizontal cells are presumed to be tuned to capture or enhance specific attributes of a visual scene – color processing, brightness contrast, temporal processing, signal enhancement and integration, and adaptation mechanisms. Ultimately, these processed and filtered signals from the retina are transmitted to higher-order visual centers, such as the lateral geniculate nucleus and the primary visual cortex of the brain, where the information is optimized to form our perceptions of the visual environment.

Acknowledgments

The authors are grateful to Dr. William H. Ridder for reading the text and providing helpful comments and Bryan Chen for assistance with drawings.

See also: The Circadian Clock in the Retina Regulates Rod and Cone Pathways; Information Processing: Amacrine Cells; Information Processing: Bipolar Cells; Information Processing: Ganglion Cells; Information Processing in the Retina; Morphology of Interneurons: Amacrine Cells; Morphology of Interneurons: Bipolar Cells; Morphology of Interneurons: Horizontal Cells; Morphology of Interneurons: Interplexiform Cells; Phototransduction: Phototransduction in Cones; Phototransduction: Phototransduction in Rods.

Further Reading

Bloomfield, S. A. and Dacheux, R. F. (2001). Rod vision: Pathways and processing in the mammalian retina. Progress in Retinal and Eye Research 20: 351–384.

Dowling, J. E. (1999). Retinal processing of visual information. Brain Research Bulletin 50: 317.

Falk, G. and Shiells, G. (2006). Synaptic transmission: Sensitivity control mechanisms. In: Heckenlively, J. H., Arden, G. B., Nusinowitz, S., Holder, G., and Bach, M. (eds.) Principles and Practice of Clinical Electrophysiology of Vision, pp. 79–91. Cambridge, MA: MIT Press.

Fu, Y. and Yau, K. W. (2007). Phototransduction in mouse rods and cones. Pflugers Archiv. European Journal of Physiology 454: 805–819.

Kolb, H. (2006). Functional organization of the retina. In: Heckenlively, J. H., Arden, G. B., Nusinowitz, S., Holder, G., and Bach, M. (eds.) Principles and Practice of Clinical Electrophysiology of Vision, pp. 47–64.

Cambridge, MA: MIT Press.

Kolb, H. and Famiglietti, E. V. (1974). Rod and cone pathways in the inner plexiform layer of cat retina. Science 186: 47–49.

Masland, R. H. (2001). The fundamental plan of the retina. Nature Neuroscience 4: 877–886.

Nickle, B. and Robinson, P. R. (2007). The opsins of the vertebrate retina: Insights from structural, biochemical, and evolutionary studies. Cellular and Molecular Life Sciences 64: 2917–2932.

Pugh, E. N., Jr. and Lamb, T. D. (1993). Amplification and kinetics of the activation steps in phototransduction. Biochimica et Biophysica Acta 1141: 111–149.

Schmidt, T. M., Taniguchi, K., and Kofuji, P. (2008). Intrinsic and extrinsic light responses in melanopsin-expressing ganglion cells during mouse development. Journal of Neurophysiology 100: 371–384.

Volgyi, B., Deans, M. R., Paul, D. L., and Bloomfield, S. A. (2004). Convergence and segregation of the multiple rod pathways in mammalian retina. Journal of Neuroscience 24: 11182–11192.

Wassle, H. (2004). Parallel processing in the mammalian retina.

Nature Reviews Neuroscience 5: 747–757.

Glossary

Anastamosis – A network of streams that both branch out and reconnect forming a communication between two blood vessels or other tubular structures.

Autoregulation – The intrinsic ability of a system to maintain constant blood flow despite changes in perfusion pressure and local vascular parameters to maintain homeostasis.

Choriocapillaris – A layer of capillaries in the choroid immediately adjacent to Bruch’s membrane. Central retinal artery – A branch of the ophthalmic artery which pierces the optic nerve close to the globe, sending branches to the internal surface of the retina.

Extraocular muscles – A group of six muscles that control the movements of the eye, including the superior, inferior, lateral, and medial recti, and the superior and inferior obliques.

Fenestration – From the Latin word for window (fenestra), a fenestration is an opening in a wall or membrane.

Hemodynamics – The study of the forces generated by the heart and the flow of blood through the cardiovascular system.

Ophthalmic artery – A branch of the internal carotid artery which enters the orbit through the optic canal, along with the optic nerve, to supply structures in the orbit.

Poiseuille’s law – A physical law that describes slow, viscous, incompressible flow through a circular cross section. It states that for a laminar, nonpulsatile fluid flow through a uniform straight tube, the vascular resistance is inversely proportional to the fourth power of the radius of a vessel, and is directly proportional to the blood viscosity and length of the vessel.

Retrobulbar vessels – Blood vessels behind the eye.

Introduction

A thorough understanding of vascular anatomy is critical to appreciate the physiology of the optic nerve head (ONH). The study of blood flow and the metabolism of

the eye are also important in understanding the role of the circulatory system in various eye diseases. The arterial supply to the optic nerve has been widely investigated; however, the precise anatomy of the anterior optic nerve microvasculature remains difficult to ascertain. Detailed assessment of this anatomy is limited by its small vessel caliber, its complex three-dimensional structure, and the relative inaccessibility of the microvascular bed. Although the evaluation of ocular hemodynamics continues to improve with the development of new imaging technologies, current techniques for measuring optic nerve blood flow do not directly evaluate the optic nerve. We summarize the vascular anatomy of the ONH, retina, and choroid, the regulation of blood flow in the ONH, and several imaging techniques used to measure blood flow in the eye.

Anatomy of the Vascular Supply

The ophthalmic artery (OA), which is the first branch of the internal carotid artery, provides the vast majority of the ocular blood supply (Figure 1). The OA enters the orbit through the optic canal and, in most individuals, runs inferolaterally to the optic nerve. After coursing nasally and anteriorly, the OA runs superior to the optic nerve, where it gives off most of its major branches. These branches include vessels to each of the extraocular muscles, the central retinal artery (CRA), and the posterior ciliary arteries (PCAs) (Figure 2). There are usually two to three PCA trunks, each dividing into approximately 10–20 short PCAs before, or, occasionally after, penetrating the sclera. The short PCAs supply the posterior choriocapillaris, peripapillary choroid, and the majority of the anterior optic nerve. The medial and temporal long PCAs pierce the sclera about 3–4 mm nasally and temporally from the optic nerve (Figure 2). They then travel anteriorly within the suprachoroidal space, along the horizontal meridians of the globe. Typically, the long PCAs divide in the vicinity of the ora serrata to supply the iris, ciliary body, and the anterior region of the choroid.

The CRA branches directly from the OA to pierce the medial aspect of the optic nerve sheath approximately 10–15 mm behind the globe. The CRA courses adjacent to the central retinal vein (CRV) through the center of the optic nerve. It emerges from the optic nerve within the globe, where it branches into four major vessels: the arteriola nasalis retinae superior, arteriola nasalis retinae inferior, arteriola temporalis retinae superior, and arteriola temporalis retinae inferior.

The vasculature of the eye can be divided into two distinct systems: the retinal system and the uveal system. The retinal system provides blood flow to the inner twothirds of the retina. The choroid and ciliary body are nourished by the uveal system. The retinal pigment epithelial layer, which is located between the retina and choroid, actively exchanges nutrients and metabolic waste products between the retina and the choroid. Thus, the outer layers of the retina receive their blood flow via the uveal system.

Retina

The retina receives its arterial blood supply from two distinct sources. The CRA provides blood flow to the inner two-thirds of the retina. The CRA branches on the surface of the optic disk, typically producing four main trunks which lie within the nerve fiber layer. Each trunk supplies its respective quadrant of the retina. The outer

one-third of the retina, including the photoreceptors and bipolar cells, receives nourishment from the underlying choroid, specifically the choriocapillaris. Nutrients are actively transported between the choroid and retina via the retinal pigment epithelium. In approximately 30% of the people, a cilioretinal artery is present. Typically a branch of a ciliary artery, this vessel supplies a variably sized region of the retina temporal to the optic nerve. When present, the cilioretinal artery is an end artery, and therefore its territory receives no additional blood supply from any other vessels.

Retinal capillaries run parallel to the retinal nerve fiber layer, eventually coalescing into retinal veins, which empty into the CRV. The CRV exits the eye through the optic nerve, running parallel to the CRA. Once in the optic nerve, the CRV receives additional intraneural tributaries, and eventually empties into the superior ophthalmic vein. Although the CRV is normally the only outflow channel

for retinal circulation, potential anastamoses exist between the retinal and choroidal circulation. These alternate pathways are significant in the case of a CRV occlusion.

Choroid

The choroid supplies the outer retina with nutrients and maintains the temperature and volume of the eye. The choroidal circulation, which accounts for 85% of the total blood flow in the eye, is a high-flow system with relatively low oxygen content. The choroidal circulation is controlled mainly by sympathetic innervation and is considered not to be autoregulated. This lack of autoregulation makes the choroid more dependent on the ocular perfusion pressure.

The short PCAs supply the posterior choroid and the peripapillary region, while the anterior parts of the choroid are supplied by the long PCAs and the anterior ciliary artery. The anterior ciliary artery is a branch from the OA which accompanies the rectus muscle anteriorly to supply the iris and the anterior choriocapillaries.

The outer choroid, known as Haller’s layer, is composed of large caliber, nonfenestrated, vessels. The inner choroid is referred to as Satler’s layer, and is composed of significantly smaller vessels. The choriocapillaries of the innermost choroid are composed of richly anastomotic, fenestrated capillaries. The capillaries of the choriocapillaries are

separate and distinct from the capillary bed of the anterior optic nerve.

Venous drainage from the choriocapillaries is primarily through the four vortex veins. Minor drainage also occurs through the ciliary body and the anterior ciliary vein. Venous anastomoses are frequent in the choroid. The vortex veins drain into the inferior and superior ophthalmic veins, which then exit the orbit through the superior and inferior orbital fissures, respectively.

Optic Nerve

The anterior optic nerve is divided into four anatomical regions: the superficial nerve fiber layer, the prelaminar layer, the laminar region, and the postlaminar region (Figure 3). The arterial supply to the ONH is derived from branches of the OA. The short PCAs penetrate the perineural sclera at the posterior aspect of the globe to supply the peripapillary choroid and anterior ONH. The circle of Zinn-Haller is a noncontinuous arterial circle surrounding the ONH within the perineural sclera. Formed by a network of small branches of the short PCAs, the circle of Zinn-Haller provides multiple perforating branches to various regions of the anterior optic nerve, peripapillary choroid, and pial arterial system. The capillaries of the anterior ONH are nonfenestrated, contain tight junctions, and form a rich anastomotic plexus. Some investigators surmise that the division of the short PCAs into branches

that supply the choroid and those supplying the ONH form the watershed zone near the ONH.

The superficial nerve fiber layer, which is continuous with the nerve fiber layer of the retina, receives its blood supply from recurrent arterioles arising from branches of the retinal arteries (Figure 4). These vessels, referred to as epipapillary vessels, originate in the peripapillary nerve fiber layer and run toward the center of the ONH. The temporal nerve fiber layer may receive additional arterial contribution from the cilioretinal artery when present.

Immediately posterior to the nerve fiber layer is the prelaminar region, which lies adjacent to the peripapillary choroid. In this region, ganglionic axons are grouped into bundles, surrounded by glial tissue septa, as they prepare for passage posteriorly through the lamina cribrosa. The prelaminar region is supplied primarily by branches of the short PCAs and, when present, by branches of the circle of Zinn-Haller (Figure 5). The amount of choroidal contribution may be difficult to determine, as there are branches from both the circle of Zinn-Haller and the short PCAs which course through the choroid and ultimately supply the optic nerve in this region. These vessels do not originate in the choroid, but merely pass through it. The choroid contributes little, if any, blood supply to this area of the ONH.

The laminar region is continuous with the sclera and is composed of fenestrated connective tissue lamellae which allow the passage of neural fibers through the sclera. This region, called the lamina cribrosa, receives its blood supply either from centripetal branches of the short PCAs or from branches of the circle of Zinn-Haller (Figure 6). These branches pierce the outer aspect of the lamina cribrosa before branching centrally to form an intraseptal capillary network throughout connective tissue. The larger peripapillary choroidal vessels occasionally contribute small arterioles to the lamina cribrosa region.

The retrolaminar region lies posterior to the lamina cribrosa, and is discernible by the beginning of the axonal myelination. Surrounded by the meninges of the central nervous system (CNS), the retrolaminar region is supplied primarily by branches of the pial arteries and the short PCAs (Figure 7). The pial system is an abundant anastomotic network fed by the OA, the circle of Zinn-Haller, and recurrent branches of the short PCAs. The pial branches are located within the pia matter and extend centripetally to perfuse the axons of the optic nerve. In addition, the CRA occasionally contributes small branches within the retrolaminar optic nerve.

Like that of the retina, the venous drainage from the ONH is through the CRV. In the superficial nerve fiber

layer, blood is drained by small, converging veins that empty into the CRV. In the other layers of the ONH, centripetal veins serve as tributaries, eventually emptying into the CRV. In the prelaminar region, there is also a noteworthy contribution from the peripapillary choroidal veins. Small portions of the peripheral region of the ONH may partially drain into the pial venous network, which ultimately joins together with the CRV as well.

Histology of Blood Vessels in the Optic

Nerve

The anterior optic nerve is composed of nerve axons, neuroglia, blood vessels, and connective tissue. Largecaliber arteries of the optic nerve contain a muscularis layer, composed of multiple layers of smooth muscle, surrounded by the adventitia. The latter consists of

circumferential collagen fibers which blend with fibers from the perivascular space. On its luminal surface, the muscularis layer is separated from the endothelium by an inner elastic layer. The basement membrane lies

between the endothelial cells and blends with the internal elastic lamina.

Arterioles of the optic nerve are much smaller in diameter, and have a single layer of smooth muscle.