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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    12 Retina and Vitreous

    Part I: Fundamentals and Diagnostic Approaches

    Chapter 01: Basic Anatomy

    Neurosensory Retina

    Retinal Layers and Neurosensory Elements

    The layers of the retina can be seen in cross-sectional histologic preparations, and most layers can be identified with spectral-domain optical coherence tomography (SD-OCT) (see Activity 2-1). The layers of the retina as seen on histologic section, in order from the inner to outer retina, are listed here (Fig 1-4):

    Figure 1-3 Schematic of the ora serrata, showing an ora bay and dentate process. Meridional folds are pleats of redundant retina. Tears may occur at the posterior end of such folds.

    (Used with permission from Federman JL, Gouras P, Schubert H, et al. Retina and vitreous. In: Podos SM, Yanoff M, eds. Textbook of Ophthalmology. Vol 9. London: Mosby; 1988.)

    • internal limiting membrane (ILM)

    • nerve fiber layer (NFL; the axons of the ganglion cell layer)

    • ganglion cell layer (GCL)

    • inner plexiform layer (IPL)

    • inner nuclear layer (INL)

    • middle limiting membrane (MLM)

    • outer plexiform layer (OPL)

    • Henle fiber layer (HFL)

    • outer nuclear layer (ONL; the nuclei of the photoreceptors)

    • external limiting membrane (ELM)

    • rod and cone inner segments (IS)

    • rod and cone outer segments (OS)

    To reach the photoreceptors, light must travel through the full thickness of the retina. The density and distribution of photoreceptors vary with their topographic location. In the fovea, densely packed cones are predominantly red- and green-sensitive, with a density exceeding 140,000 cones/mm2. The foveola has no rods; the fovea contains only photoreceptors, rods and cones, and processes of Müller cells. The number of cone photoreceptors decreases rapidly in areas farther away from the center, even though 90% of cones overall reside outside the foveal region. The rods have their greatest density in a zone lying approximately 4 mm from the foveal center, or 12° from fixation, where they reach a peak density of about 160,000 rods/mm2. The density of rods also decreases toward the periphery. A small area of high rod concentration (176,000 rods/mm2) has been found in the superior macula. The arrangement of rods and cones can be visualized with noninvasive adaptive optics imaging (Fig 1-5).

    Figure 1-4 Cross-sectional photomicrographs of peripheral macular and foveal retina (H&E stain). A, Cross section of the retina and choroid, showing the layers of the retina (labeled).B, In the fovea, the inner cellular layers are laterally displaced, and there is an increased density of pigment in the retinal pigment epithelium (RPE). Note that on the right edge of the image, the inner cellular layers are laterally displaced. This allows the incident light to fall directly on to the photoreceptors, avoiding the inner retinal layers, thereby reducing the potential for scattering of light. An additional characteristic of the foveal region is that there is increased density of pigment in the RPE.

    (Courtesy of Ralph Eagle, MD.)

    The light-sensitive molecules in rods and cones are derived from vitamin A and are contained in the disc membranes of the photoreceptor outer segments. The discs are attached to a cilium, which is rooted through neurotubules in the ellipsoid and myoid of the inner segment. The ellipsoid, which is adjacent to the cilium, contains mitochondria and is responsible for the cone shape. The myoid, which is closer to the photoreceptor nucleus, contains endoplasmic reticulum. The mitochondria, cilia, and inner discs together form the inner-outer segment junction, which provides evidence of the origin of the photoreceptor as a modified sensory cilium prone to the full range of ciliopathies. Rod outer segments may contain up to 1000 discs stacked like coins. These discs are renewed in and shed from the outer retina and are phagocytosed by the retinal pigment epithelium (RPE) for processing and recycling of components (Fig 1-6).

    Figure 1-5 Comparison of a conventional fundus photograph (A) and confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images of a healthy left-eye macula. The white box on the fundus photo that is closer to the fovea is 0.5° from fixation and represents a 300 × 300-micron area of macula. The corresponding AOSLO image of the retina within that white box (B) shows cones that are smaller and very tightly packed; no rods are visible. The white box on the fundus photo that is closer to the optic nerve is 7° from fixation and also represents a 300 × 300-micron area of macula. The corresponding AOSLO image (C) shows cones that are larger and less densely packed; intervening rods are starting to become visible.

    (Courtesy of Mina M. Chung, MD, and Hongxin Song, MD, PhD.)

    Cone photoreceptors have a 1-to-1 synapse with a type of bipolar cell known as a midget bipolar cell. Other types of bipolar cells also synapse with each cone. Conversely, more than 1 rod—and sometimes more than 100 rods—converge on each bipolar cell. Bipolar cells, the first neurons of the visual pathway, synapse with ganglion cells, the second neurons of the visual pathway in the IPL. The ganglion cells summate responses from bipolar and amacrine cells and develop action potentials that are conducted to the dorsolateral geniculate nucleus and the third neuron in the brain. Amacrine cells on the inside of the INL help process signals by responding to specific alterations in retinal stimuli, such as sudden changes in light intensity or the presence of certain sizes of stimuli. The outside of the INL is composed of horizontal cells. In the NFL, axons of the GCL course along the inner portion of the retina to form the optic nerve, a brain tract. The ILM, which is formed by the footplates of Müller cells, is attached to the posterior cortical gel of the vitreous (Fig 1-7).

    Figure 1-6 Schematic of a cone cell (left) and a rod cell (right) in the peripheral retina. C = cilium; CP = cone cell pedicle; DM = membranous discs; ELM = external limiting membrane; G = Golgi apparatus; IF = inner fiber; IS = inner segment; M = mitochondria; MV = microvilli of pigment epithelial cells; N = nucleus; OF= outer fiber; OS = outer segment; P = perikaryon; PC = processus calycoides; PE = pigment epithelium; R = free ribosomes; RER = rough endoplasmic reticulum; RF = rootlet fiber; S = rod cell spherule; SER = smooth endoplasmic reticulum.

    (Used with permission from Krebs W, Krebs I. Primate Retina and Choroid. Atlas of Fine Structure in Man and Monkey. New York: Springer Verlag; 1991.)

    Two additional intraretinal “membranes” identified by histologists, the ELM and MLM, are actually junctional systems, not true membranes. At the outer extent of the Müller cells, zonular attachments between photoreceptors and Müller cells create the ELM, a structure visible with both light microscopy and OCT. Thus, the Müller cells whose nuclei reside in the INL course through almost the entire thickness of the retina. The inner third of the OPL has a linear density in which synaptic and desmosomal connections occur between the photoreceptor inner fibers and the processes of the bipolar cells. This linear density, which is also apparent with OCT, is the junctional system that has been called the MLM.

    Figure 1-7 Schematic of the neuronal connections in the retina and participating cells.

    (Illustration by Mark Miller.)

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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