Visual System

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Chapter 1 Visual System

The visual system takes in information from the environment in the form of light and analyzes and interprets it. This process of sight and visual perception involves a complex system of structures, each of which is designed for a specific purpose. The organization of each structure enables it to perform its intended function.

The eye houses the elements that take in light rays and changes them to a neural signal; it is protected by its location within the bone and connective tissue framework of the orbit. The eyelids cover and protect the anterior surface of the eye and contain glands that produce the lubricating tear film. Muscles, attached to the outer coat of the eye, control and direct the globe’s movement, and the muscles of both eyes are coordinated to provide binocular vision. A network of blood vessels supplies nutrients, and a complex system of nerves provides sensory and motor innervation to the eye and surrounding tissues and structures. The neural signal that carries visual information passes through a complex and intricately designed pathway within the central nervous system, enabling an accurate view of the surrounding environment. This information, evaluated by a process called visual perception, influences myriad decisions and activities.

This book examines the macroscopic and microscopic anatomy and physiology of the components in this complex system and the structures that support it.

The Eye

Anatomic Features

The eye is a special sense organ made up of three coats, or tunics, as follows:

Within this globe are three spaces: the anterior chamber, posterior chamber, and vitreous chamber. The crystalline lens is located in the region of the posterior chamber (Figure 1-1).

image

Figure 1-1 The visual system.

(From Kronfeld PC: The human eye, Rochester, NY, 1943, Bausch & Lomb Press.)

The outer dense connective tissue of the eye provides protection for the structures within and maintains the shape of the globe, providing resistance to the pressure of the fluids inside. The sclera is the opaque white of the eye and is covered by the transparent conjunctiva. The transparent cornea allows light rays to enter the globe and, by refraction, helps bring these light rays into focus on the retina. The region in which the transition from cornea to sclera and conjunctiva occurs is the limbus.

The vascular layer of the eye is the uvea, which is made up of three structures, each having a separate function but all are interconnected. Some of the histologic layers are continuous throughout all three structures and are derived from the same embryonic germ cell layer. The iris is the most anterior structure, acting as a diaphragm to regulate the amount of light entering the pupil. The two iris muscles control the shape and diameter of the pupil and are supplied by the autonomic nervous system. Continuous with the iris at its root is the ciliary body, which produces the components of the aqueous humor and contains the muscle that controls the shape of the lens. The posterior part of the uvea, the choroid, is an anastomosing network of blood vessels with a dense capillary network; it surrounds the retina and supplies nutrients to the outer retinal layers.

The neural tissue of the retina, by complex biochemical processes, changes light energy into a signal that can be transmitted along a neural pathway. The signal passes through the retina, exits the eye through the optic nerve, and is transmitted to various parts of the brain for processing.

The interior of the eye is made up of three chambers. The anterior chamber is bounded in front by the cornea and posteriorly by the iris and anterior surface of the lens. The posterior chamber lies behind the iris and surrounds the equator of the lens, separating it from the ciliary body. The anterior and posterior chambers are continuous with one another through the pupil, and both contain aqueous humor that is produced by the ciliary body. The aqueous humor provides nourishment for the surrounding structures, particularly the cornea and lens. The vitreous chamber, which is the largest space, lies adjacent to the inner retinal layer and is bounded in front by the lens. This chamber contains a gel-like substance, the vitreous humor.

The crystalline lens is located in the area of the posterior chamber and provides additional refractive power for accurately focusing images onto the retina. The lens must change shape to view an object that is close to the eye, through the mechanism of accommodation.

Anatomic Directions and Planes

Anatomy is an exacting science, and specific terminology is basic to its discussion. The following anatomic directions should be familiar (Figure 1-2):

image

Figure 1-2 Anatomic directions.

(From Palastanga N, Field D, Soames R: Anatomy and human movement, Oxford, UK, 1989, Butterworth-Heinemann.)

The following planes are used in describing anatomic structures (Figure 1-3):

image

Figure 1-3 Anatomic planes.

(From Palastanga N, Field D, Soames R: Anatomy and human movement, Oxford, UK, 1989, Butterworth-Heinemann.)

Because the globe is a spherical structure, references to locations can sometimes be confusing. In references to anterior and posterior locations of the globe, the anterior pole (i.e., center of the cornea) is the reference point. For example, the pupil is anterior to the ciliary body (see Figure 1-1). When layers or structures are referred to as inner or outer, the reference is to the entire globe unless specified otherwise. The point of reference is the center of the globe, which would lie within the vitreous. For example, the retina is inner to the sclera (see Figure 1-1). In addition, the term sclerad is used to mean “toward the sclera,” and vitread is used to mean “toward the vitreous.”

Refractive Conditions

If the refractive power of the optical components of the eye, primarily the cornea and lens, correlate with the distances between the cornea, lens, and retina so that incoming parallel light rays come into focus on the retina, a clear image will be seen. This condition is called emmetropia (Figure 1-4, A). No correction is necessary for clear distance vision. In hyperopia (farsightedness), the distance from the cornea to the retina is too short for the refractive power of the cornea and lens, thereby causing images that would come into focus behind the retina (Figure 1-4, B). Hyperopia can be corrected by placing a convex lens in front of the eye to increase the convergence of the incoming light rays. In myopia (nearsightedness), because the lens and cornea are too strong or, more likely, the eyeball is too long, parallel light rays are brought into focus in front of the retina (Figure 1-4, C). Myopia can be corrected by placing a concave lens in front of the eye, causing the incoming light rays to diverge.

Ophthalmic Instrumentation

Various instruments are used to assess the health and function of elements of the visual pathway and the supporting structures. This section briefly describes some of these instruments and the structures examined.

The curvature of the cornea is one of the factors that determine the corneal refractive power. A keratometer measures the curvature of the central 3 to 4 mm of the anterior corneal surface and provides information about the power and the difference in curvature between the principle meridians at that location. The smoothness of the corneal surface can also be assessed by the pattern reflected from the cornea during the measuring process. The automated corneal topographer maps the corneal surface and gives an indication of curvatures at selected points. This instrument is an important adjunct in the fitting of contact lenses in difficult cases.

The optometric physician can objectively determine the optical power of the eye with a set of lenses and a retinoscope. This instrument is beneficial also for assessing the accommodative function of the lens.

The inside of the eye, called the fundus, is examined using an ophthalmoscope, which illuminates the interior with a bright light. The retina, optic nerve head, and blood vessels can be assessed and information about ocular and systemic health obtained. This is the only place in the body in which blood vessels can be viewed directly and noninvasively. Various systemic diseases, such as diabetes, hypertension, and arteriosclerosis, can alter ocular vessels. To obtain a more complete view of the inside of the eye, topical drugs are administered to influence the iris muscles, causing the pupil to become enlarged, or mydriatic. The binocular indirect ophthalmoscope allows stereoscopic viewing of the fundus.

The outside of the globe and the eyelids can be assessed with a biomicroscope. This combination of an illumination system and a binocular microscope allows stereoscopic views of various parts of the eye. Particularly beneficial is the view of the transparent structures, such as the cornea and lens. A number of auxiliary instruments can be used with the biomicroscope to measure intraocular pressure and to view the interior of the eye.

Technologic advances have produced instrumentation that can provide three-dimensional mapping of retinal and optic nerve head surfaces and measure the thickness of specific retinal layers. Additional instrumentation can allow visualization of corneal layers, cells, and nerves and can aid in the differentiation of bacterial, viral, parasitic, and fungal infection in corneal tissue.

The visual field is the area that a person sees when looking straight ahead, including those areas seen “out of the corner of the eye.” A perimeter is used to test the extent, sensitivity, and completeness of this visual field. Computerized perimeters provide extremely detailed maps of the visual field, as well as statistical information on the reliability of the test and the probabilities of any defects.

Basic Histologic Features

Because many of the anatomic structures are discussed in this book at the histologic level, this section briefly reviews basic human histology. Other details of tissues are addressed in the pertinent chapters.

All body structures are made up of one or more of the four basic tissues: epithelial, connective, muscle, and nervous tissue. A tissue is defined as a collection of similar cells that are specialized to perform a common function.

Epithelial Tissue

Epithelial tissue often takes the form of sheets of epithelial cells that either cover the external surface of a structure or that line a cavity. Epithelial cells lie on a basement membrane that attaches them to underlying connective tissue. The basement membrane can be divided into two parts: the basal lamina, secreted by the epithelial cell, and the reticular lamina, a product of the underlying connective tissue layer.1 The free surface of the epithelial cell is the apical surface, whereas the surface that faces underlying tissue or rests on the basement membrane is the basal surface.

Epithelial cells are classified according to shape. Squamous cells are flat and platelike, cuboidal cells are of equal height and width, and columnar cells are higher than wide. Epithelium consisting of a single layer of cells is referred to as simple: simple squamous, simple cuboidal, or simple columnar. Endothelium is the special name given to the simple squamous layer that lines certain cavities. Epithelium consisting of several layers is referred to as stratified and is described by the shape of the cells in the surface layer. Only the basal or deepest layer of cells is in contact with the basement membrane, and this layer usually consists of columnar cells.

Keratinized, stratified squamous epithelium has a surface layer of squamous cells with cytoplasm that has been transformed into a substance called keratin, a tough protective material relatively resistant to mechanical injury, bacterial invasion, and water loss. These keratinized surface cells constantly are sloughed off and are replaced from the layers below, where cell division takes place.

Connective Tissue

Connective tissue provides structure and support and is a “space filler” for areas not occupied by other tissue. Connective tissue consists of cells, fibers, and ground substance. The ground substance consisting of glycoproteins and water, and the insoluble protein fibers collectively are called matrix. Connective tissue can be classified as loose or dense. Loose connective tissue has relatively fewer cells and fibers per area than dense connective tissue, in which the cells and fibers are tightly packed. Dense connective tissue can be characterized as regular or irregular on the basis of fiber arrangement.

Among the cells that may be found in connective tissue are fibroblasts (flattened cells that produce and maintain the fibers and ground substance), macrophages (phagocytic cells), mast cells (which contain heparin and histamine), and fat cells. Connective tissue composed primarily of fat cells is called adipose tissue.

The fibers found in connective tissue include flexible collagen fibers with high tensile strength, delicate reticular fibers, and elastic fibers, which can undergo extensive stretching. Collagen fibers are a major component of much of the eye’s connective tissue. These fibers are composed of protein macromolecules of tropocollagen that have a coiled helix of three polypeptide chains. The individual polypeptide chains can differ in their amino acid sequences, and the tropocollagen has a banded pattern because of the sequence differences.2 Collagen is separated into various types on the basis of such differences, and several types are components of ocular connective tissue structures.

The amorphous ground substance, in which the cells and fibers are embedded, consists of water bound to glycosaminoglycans and long-chain carbohydrates.

Brief Review of Human Cellular Physiology

The cell membrane surrounds each cell and is composed of a double layer of lipids; the hydrophobic lipid portion is in the center of the membrane and hydrophilic phosphate groups face aqueous solutions both inside and outside the cell. Cholesterol molecules found in the central fatty acid portion decrease the membrane’s permeability to water soluble molecules. Protein molecules may be embedded in both surfaces of the lipid bilayer and membrane-spanning proteins have portions both inside and outside the cell.

The cellular cytoplasm (cytosol) contains various protein fibers: microtubules are the largest and are composed of the protein tubulin; other fibers may be tissue specific—keratin fibers in epithelium, microfilaments of actin and myosin fibers in sarcoplasm, and neurofilaments in neurons. The cytoskeleton is a three-dimensional scaffolding within the cytoplasm that gives the cell structure, support, and also provides intracellular transport. The nucleus, the control center for the cell, directs cellular function and contains most of the genetic material within its DNA, which is organized into chromosomes. The genes within the chromosomes are the genome Ribosomes, granules of RNA within the cytoplasm, manufacture proteins as directed by the cellar DNA. The endoplasmic reticulum (ER) network, within the cytoplasm, provides sites for protein and lipid synthesis; smooth ER produces fatty acids, steroids, and lipids; rough ER produces proteins. Golgi apparatus modify and package proteins. Mitochondria, the power house of the cell, produce the cell’s supply of energy in the form of adenosine triphosphate (ATP). The inner wall of the double-walled mitochondria is folded into cisternae, where biochemical processes produce the ATP. Lysosomes, intracellular digestive systems containing powerful enzymes, take up bacteria or old organelles and break them down into component molecules that are reused or reabsorbed into the cytoplasm to be transported to the cell membrane and out of the cell.

Fluid and solute transport across the cell membrane can occur passively by diffusion that occurs when molecules pass from a higher to a lower concentration down the concentration gradient; no energy is expended. Channel proteins within the cell membrane create water-filled passages linking the intracellular and extracellular spaces. A million ions per second may flow through such a channel and tens of millions of ions per second can enter or exit a cell.4 These channels facilitate ion movement across the lipid bilayer and move ions, also without the expenditure of energy. Channels may be specific for ion type, molecule size, or charge (i.e., Na+ channels, K+ channels, cation channels). Channels can be gated, opening and closing in response to certain stimulants (i.e., voltage-gated, chemical-gated, ligand-gated). In facilitated diffusion, carrier proteins bind to substrates that they carry across the membrane (these are slower and selective but can carry larger molecules); they never form a direct connection between the intracellular and extracellular environments. Molecules such as glucose and amino acids are moved in this way. Active transport mechanisms use energy. Transporters and co-transporters move substance against the concentration gradient and need a steady supply of ATP. Transporting epithelia are polarized and the apical and basal membranes have differing properties; both often contain ion channels; however, the Na+/K+ ATPase pumps are generally located in the basolateral membranes. Aquaporins are bidirectional channels composed of major intrinsic proteins that specifically allow water passage but may not allow other materials to pass through the channel. Aquaporins are numerous in ocular tissues: cornea, lens, ciliary body epithelia, and retina. Membranes containing aquaporins have 100 times greater water permeability than membranes without them.5 Aquaporins may have functions other than transport; some may regulate cell migration processes and some may have a role in neural signal transduction.6

Cellular metabolic functions are complex activities maintaining the viability of the cell. Amino acids, carbohydrates, and lipids are used as building blocks in the construction of cellular components or are broken down as a source of energy. Myriad biochemical pathways and processes function in cellular metabolism and are regulated by signals from either inside or outside the cell. Integrins are membrane-spanning proteins that can carry information from the extracellular matrix into the cell and activate intracellular enzymes that then influence cellular processes. Energy for metabolic processes is supplied by ATP molecules, produced either through aerobic or anaerobic metabolism; aerobic is more efficient, with 36 to 38 molecules of ATP produced per molecule of glucose; aerobic glycolysis yields 2 ATP per molecule.

Intercellular Junctions

Intercellular junctions join epithelial cells to one another and to adjacent tissue; some are named by their type and some by their shape. Protein components of intercellular junctions include cell adhesion molecules, transmembrane proteins (occludin, claudin), junctional adhesion molecules, and associated cytoplasmic proteins.7 Junctions between cells or with connective tissue can have additional functions other than adhesion. Physical changes, such as pressure and biochemical or pharmaceutical factors, can modulate junctions and alter the junctional proteins. This allows information about changes in the extracellular environment to be relayed to the cell interior affecting intracellular processes.

In a tight (occluding) junction, the outer leaflet of the cell membrane of one cell comes into direct contact with its neighbor. Ridgelike elevations on the surface of the cell membrance fuse with complementary ridges on the surface of a neighboring cell.8 As the paired strands meet, the neighboring cell membranes are fused.9 The fibers of tight junctions are connected to the cytoskeleton within the cell.

A tight junction that forms a zone or belt around the entire cell, joining it with each of the adjacent cells is called a zonula occludens (ZO) (Figure 1-5). In these zones, row on row of interwining ridges effectively occlude the intercellular space. A substance cannot pass through a sheet of epithelium whose cells are joined by ZO by passing between the cells, but must pass through the cell.In stratified epithelia, whose surface layer is constantly being sloughed and replaced from below, ZO, if present, will be located in the surface layer. The components of the tight junction are found in increasing numbers as a cell moves from its origin in the basal layer until, finally when the cell reaches the surface, its occluding junction is complete.10 The complex formed by the junctional proteins in the ZO can be affected in some diseases, causing in a breakdown in the barrier function, allowing a pathway to open through the network. Currently, researchers are developing pharmaceuticals that will cause a temporary disruption of the barrier, and that would allow other drugs or substances to pass through the intercellular route. In some instances, ridges in a tight junction are fewer and discontinuous, resulting in a “leaky epithelium.”8

A zonula adherens (ZA), an intermediate junction, is a similarly-shaped zone. However, the adjacent plasma membranes are separated, leaving a narrow intercellular space that contains a glycoporotein material causing cell adhesion but allowing intercellular passage.12 ZA junctions produce relatively firm adhesions. Adjacent to the adhering junction are fine microfilaments that extend from a plaque just inside the membrane to filaments of the cytoskeleton, contributing to cell stability.8 A terminal bar consists of a zonula occludens and a zonula adherens side by side, with the tight junction lying nearest the cell apex.1,8

Round, buttonlike intercellular junctions are either macula occludens (MO) or macula adherens (MA), depending on the type of adhesion.

A desmosome is a strong, spotlike attachment between cells (see Figure 1-5). A dense disc or plaque is present within the cytoplasm adajcent to the plasma membrane at the site of the adherence. Hairpin loops of cytoplasmic filaments called tonofilaments extend from the disc into the cytoplasm and link to keratin filaments in the cytoskelton, contributing to cell stability. Other filaments, transmembrane linkers, cadherins, extend from the plaque across the intercellular space, holding the cell membranes together and forming a strong bond.12 The intercellular space contains an acid-rich mucoprotein that acts as a strong adhesive.8

A hemidesmosome provides a strong connection between the cell and its basement membrane and underlying connective tissue. It contains similar intracellular components; the protein complex extends through the cell membrane to attach to keratin in the basement membrane. Bundles of filaments join the intracellular plaque to underlying connective tissue matrix, often attaching to a plaque embedded in the connective tissue.10

Gap junctions are formed by a group of (usually six)proteins, called connexins, that span the cell membrane and unite with connexins of a neighboring cell, forming a channel called a connexon (see Figure 5-1).13 These narrow channels allow rapid cell-to-cell communication, i.e., passage of small molecules and ions from one cell to another. A group of cells with such connection act like a syncytium, that is, a single cell with multiple nuclei.

References

1. Krause W.J., Cutts J.H. Epithelium. In: Krause W.J., Cutts J.H., editors. Concise text of histology. Baltimore: Williams & Wilkins; 1981:27.

2. Copenhaver W.M., Kelly D.E., Wood R.L. The connective tissues. In: Copenhaver W.M., Kelly D.E., Wood R.L., editors. Bailey’s textbook of histology. ed 17. Baltimore: Williams & Wilkins; 1978:142.

3. Krause W.J., Cutts J.H. Nervous tissue. In: Krause W.J., Cutts J.H., editors. Concise text of histology. Baltimore: Williams & Wilkins; 1981:137.

4. Mergler S., Pleyer U. The human corneal endothelium: new insights into electrophysiology and ion channels. Prog Retin Eye Res. 2007;26:359-378.

5. Agre P., Kozono D. Aquaporin water channels: molecular mechanisms for human diseases. FEBS Lett. 2003;555:72-78.

6. Verkman A.S., Ruiz-Ederra J., Levin M.H. Functions of aquaporins in the eye. Prog Retin Eye Res. 2008;27:420-433.

7. Teranishi S., Kimura K., Kawamoto K., et al. Protection of human corneal epithelial cells from hypoxia-induced disruption of barrier function by keratinocyte growth factor. Invest Ophthalmol Vis Sci. 2008;49:2432-2437.

8. Copenhaver W.M., Kelly D.E., Wood R.L. Epithelium. In: Copenhaver W.M., Kelly D.E., Wood R.L., editors. Bailey’s textbook of histology. ed 17. Baltimore: Williams & Wilkins; 1978:103.

9. Yoshida Y., Ban Y., Kinoshita S. Tight junction transmembrane protein claudin subtype expression and distribution in human corneal and conjunctival epithelium. Invest Ophthalmol Vis Sci. 2009;50:2103-2108.

10. Suzuki K., Tanaka T., Enoki M., et al. Coordinated reassembly of the basement membrane and junctional proteins during corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 2000;41:2495-2500.

11. Delamere N.A. Ciliary body and ciliary epithaliu. In: Fischbarg J., editor. The biology of the eye. Amsterdam, The Netherlands: Elsevier; 2006:127-148.

12. Fawcett D.W., Jensh R.P. Bloom & Fawcett concise histology. London: Chapman & Hall; 1997. p 19

13. Shurman D.L., Glazewski L., Gumpert A., Zieske J.D., Richard G. In vivo and in vitro expression of connexins in the human corneal epithelium. Invest Ophthalmol Vis Sci. 2005;46:1957-1965.