Figure 2-28 A, Cross section of retina illustrating the layers of retina and

approximate location of blood supply to these layers. B, Cell types and histologic
layers in the human retina. The basic relationship between rod (R) and cone (C)
photoreceptors as well as bipolar (B), horizontal (H), amacrine (A), inner plexiform
cell (I), and ganglion (G) neurons is depicted. Note that the Müller cell (M) extends
across almost the whole thickness of the retina; the apical processes of Müller cells
form the external limiting membrane; the foot processes of Müller cells partially
form the internal limiting membrane. (Part A modified with permission from
D’Amico DJ. Diseases of the retina. N Engl J Med. 1994;331:95–106. Part B
illustration by Christine Gralapp.)

Neuronal elements
The photoreceptor layer of the neurosensory retina consists of highly specialized
neuroepithelial cells called rods and cones. Each photoreceptor cell consists of an
outer segment and an inner segment. The outer segments, surrounded by a
mucopolysaccharide matrix, make contact with the apical processes of the RPE.
Tight junctions or other intercellular connections do not exist between the
photoreceptor cell outer segments and the RPE. The factors responsible for keeping
these layers in apposition are poorly understood but probably involve active
transport.
The rod photoreceptor consists of an outer segment that contains multiple laminated
discs resembling a stack of coins and a central connecting cilium. The microtubules
of the cilium have a 9-plus-2 cross-sectional configuration rather than the 9-plus-2
configuration found in motile cilia. The rod inner segment is subdivided into 2
additional elements: (1) an outer ellipsoid containing numerous mitochondria and
(2) an inner myoid containing a large amount of glycogen; the myoid is continuous
with the main cell body, where the nucleus is located (Fig 2-29). The inner portion
of the cell contains the synaptic body, or spherule, of the rod, which is formed by a
single invagination that accommodates 2 horizontal cell processes and 1 or more
central bipolar dendrites (Fig 2-30). The outer segments of the cones have a different
morphology depending on their location in the retina.

Figure 2-29 Rod and cone photoreceptor cells. (Illustration by Sylvia Barker.)

Figure 2-30 Synaptic bodies of photoreceptors. A, Cone pedicle with synapses to

several types of bipolar cells. B, Rod spherule with synapses to bipolar cells. FB =
Flat bipolar; FMB = Flat midget bipolar; H = horizontal cell processes; IMB =
invaginating midget bipolar; RB = rod bipolar. (Illustration by Sylvia Barker.)

The extrafoveal cone photoreceptors of the retina have conical ellipsoids and
myoids, and their nuclei tend to be closer to the external limiting membrane than are
the nuclei of the rods. Although the structure of the outer segments of the rods and
cones is similar, at least 1 important di_erence exists. Rod discs are not attached to
the cell membrane; they are discrete structures. Cone discs are attached to the cell
membrane and are thought to be renewed by membranous replacement. The cone
synaptic body, or pedicle, is more complex than the rod spherule. Cone pedicles
synapse with other rods and cones as well as with horizontal and bipolar cell
processes. Foveal cones have cylindrical inner segments similar to rods but
otherwise are cytologically identical to extrafoveal cones. Horizontal cells make
synaptic connections with many rod spherules and cone pedicles; they also extend
cell processes horizontally throughout the outer plexiform layer. Bipolar cells are
oriented vertically. Their dendrites synapse with either rod or cone synaptic bodies,
and their axons make synaptic contact with ganglion cells and amacrine cells in the
inner plexiform layer.
The axons of the ganglion cells bend to become parallel to the inner surface of the
retina, where they form the nerve fiber layer and later the axons of the optic nerve.
Each optic nerve has more than 1 million optic nerve fibers. The nerve fibers from
the temporal retina follow an arcuate course around the macula to enter the superior
and inferior poles of the optic disc. The papillomacular fibers travel
straight to the optic nerve from the fovea. The nasal axons also pursue a radial
course. The visibility of the nerve fibers is enhanced when they are viewed
ophthalmoscopically using green (red-free) illumination.

The neuronal elements and their connections in the retina are highly complex. Many
types of bipolar, amacrine, and ganglion cells exist. The neuronal elements of more
than 120 million rods and 6 million cones are interconnected, and signal processing
within the neurosensory retina is significant.

Glial elements
Müller cells are glial cells that extend vertically from the external limiting membrane
inward to the internal limiting membrane. Their nuclei are located in the inner
nuclear layer. Müller cells, along with the other glial elements (the fibrous and
protoplasmic astrocytes and microglia), provide structural support and nutrition to
the retina and are crucial to normal physiology.

Vascular elements
The inner portion of the retina is perfused by branches of the central retinal artery.
In addition, a cilioretinal artery can branch from the ciliary circulation to supply the
macula; studies show this occurs in approximately 18%–32% of eyes.

The retinal blood vessels are analogous to the cerebral blood vessels and maintain
the inner blood–retina barrier. This physiologic barrier is due to the single layer of
nonfenestrated endothelial cells, whose tight junctions are impervious to tracer
substances such as fluorescein and horseradish peroxidase. A basal lamina covers
the outer surface of the endothelium. The basement membrane contains an
interrupted layer of pericytes, or mural cells, surrounded by their own basement
membrane material.

Müller cells and other glial elements are generally attached to the basal lamina of
retinal blood vessels. Retinal blood vessels lack an internal elastic lamina and the
continuous layer of smooth muscle cells found in other vessels in the body. Smooth
muscle cells are occasionally present in vessels near the optic nerve head. They
become a more discontinuous layer as the retinal arterioles pass farther out to the
peripheral retina. The retinal blood vessels do not ordinarily extend deeper than the
middle limiting membrane. Where venules and arterioles cross, they share a
common basement membrane. Venous occlusive disorders are common at
arteriovenous crossings.

Stratification of the neurosensory retina

The neurosensory retina can be subdivided into several layers (see Fig 2-28). The
outermost layer, which is located next to the RPE, is the external limiting membrane
(ELM). It is not a true membrane and is formed by the attachment sites of adjacent
photoreceptors and Müller cells. It is highly fenestrated.

The outer plexiform layer (OPL) is composed of the interconnections between the
photoreceptor synaptic bodies and the horizontal and bipolar cells. In the macular
region, the OPL is thicker and contains more fibers, because the axons of the rods
and cones become longer and more oblique as they deviate from the fovea. In this
region, the OPL is known as the Henle fiber layer (Fig 2-31). At the edge of the
foveola, it lies almost parallel to the internal limiting membrane. The inner nuclear
layer (INL) contains nuclei of bipolar, Müller, horizontal, and amacrine cells.

Figure 2-31 Schematic section through the fovea. FAZ = foveal avascular zone;
GCL = ganglion cell layer; INL = inner nuclear layer; IPL = inner plexiform layer;
IS = inner segment of the photoreceptor; NFL = nerve fiber layer; ONL = outer
nuclear layer; OPL = outer plexiform layer (Henle fiber layer); OS = outer segment
of the photoreceptors; RPE = retinal pigment epithelium.
(Illustration by Sylvia Barker.)

The next region is formed by a zone of desmosome-like attachments in the region of

the synaptic bodies of the photoreceptor cells. The retinal blood vessels ordinarily
do not extend beyond this point. The inner plexiform layer (IPL) consists of axons
of the bipolar and amacrine cells and dendrites of the ganglion cells and their
synapses. The ganglion cell layer (GCL) is made up of the cell bodies of the ganglion
cells that lie near the inner surface of the retina. The nerve fiber layer (NFL) is
formed by axons of the ganglion cells. Normally, these axons do not become
myelinated until after they pass through the lamina cribrosa of the optic nerve.

Similar to the ELM, the internal limiting membrane (ILM) is not a true membrane.
It is formed by the footplates of the Müller cells and attachments to the basal lamina.
The basal lamina of the retina is smooth on the vitreal side but appears undulating
on the retinal side, where it follows the contour of the Müller cells. The thickness of
the basal lamina varies. Overall, cells and their processes in the retina are oriented
perpendicular to the plane of the RPE in the middle and outer layers but parallel to
the retinal surface in the inner layers. For this reason, deposits of blood or exudates
tend to form round blots in the outer layers (where small capillaries are found) and
linear or flame-shaped patterns in the nerve fiber layer. At the fovea, the outer layers
also tend to be parallel to the surface (Henle fiber layer). As a result, radial or star-
shaped patterns may arise when these extracellular spaces are filled with serum and
exudate.

Macula
The terms macula, macula lutea, posterior pole, area centralis, fovea, and foveola
have created confusion among anatomists and clinicians. Clinical retina specialists
tend to regard the macula as the area within the temporal vascular arcades.
Histologically, it is the region with more than 1 layer of ganglion cell nuclei (Figs
2-32, 2-33; also see Fig 2-28). See BCSC Section 12, Retina and Vitreous, for further
detail. The name macula lutea (which means yellow spot) derives from the yellow
color of the central retina in dissected cadaver eyes. This color is due to the presence
of carotenoid pigments, which are located chiefly in the Henle fiber layer. Two major
pigments—zeaxanthin and lutein—have been identified whose proportions vary
with their distance from the fovea. In the central area (0.25 mm from the fovea), the
lutein-to-zeaxanthin ratio is 1:2.4, and in the periphery (2.2–8.7 mm from the fovea),
the ratio is greater than 2:1. This variation in pigment ratio corresponds to the rod-
to-cone ratio. Lutein is more concentrated in rod-dense areas of the retina;
zeaxanthin is more concentrated in cone-dense areas. Lipofuscin, the yellow age
pigment, has been observed in the cytoplasm of the perifoveal
ganglion cells by electron microscopy.