Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye.

Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 4–10

Anatomy and Function of the Eye

Henry J. Kaplan
Department of Ophthalmology and Visual Science, University of Louisville,
Louisville, Ky., USA

Abstract
This text is not a generic book on the immunology of the eye, but instead is based on
the theme of ocular immune privilege. In subsequent chapters it is apparent that the immuno-
logic privilege within the eye is dependent upon novel anatomic and physiologic properties
of the organ. The focus of this chapter is to provide a concise description of both the function
and anatomy of the normal eye.
Copyright © 2007 S. Karger AG, Basel

Vision

The greatest fear expressed by all patients is the loss of vision and the fear
of blindness. The majority of patients have less of a concern about death from
cancer, stroke or heart attack. The clarity of vision is recorded as visual acuity,
which is a measurement of the smallest object a person can identify at a given
distance. A patient with normal vision will have visual acuity of 20/20 – i.e. at
20 feet the patient can see a letter that subtends an angle of 20⬚. One definition
of legal blindness is a visual acuity ⱕ20/400 – i.e. the smallest object the
patient can identify at 20 feet is a letter that subtends an angle of 400⬚ [1].
Light rays entering the eye are focused on the neurosensory retina, specif-
ically the fovea, by the two major refractive surfaces of the eye – the cornea and
the lens (fig. 1). Approximately two thirds of the refractive power of the eye are
provided by the cornea with the remaining one third provided by the lens. If the
axial lens of the eye is too short, the light rays entering the eye will be focused
at a point (focal point) behind the fovea – i.e. far sighted or hyperopia. In
contrast, if the axial lens of the eye is too long, the focal point or the incident
light rays will be focused in front of the fovea – i.e. near sighted or myopia.
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 Anterior chamber
Iris Cornea

Conjunctiva Pupil
Limbus
Posterior chamber Schlemm’s canal
Zonules Lens
Ciliary body

Sclera

Choroid

Retina

Vitreous cavity

Optic disc

Fovea
Macula
Central retinal
artery and vein
Dura mater
Optic nerve

Fig. 1. A schematic cross-section of the eye demonstrating its major anatomical fea-
tures (reproduced with permission of the American Academy of Ophthalmology [1]).

Spectacles, contact lenses, and refractive surgery can correct these optical
errors and achieve normal distance vision.
Light rays from an object at a distance (i.e. ⬎20 feet) are considered paral-
lel to the visual axis of the eye. An object that is closer than 20 feet requires
increased refractive power from the eye to maintain the focal point on the fovea
of the retina. This increase in refractive power for the eye is accomplished by
the ability of the ciliary muscle to contract and the lens to become more convex,
a process called accommodation. The lens of every eye undergoes progressive
hardening with age with the loss of the ability to change its shape. This loss of
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accommodation is experienced as a decreased ability to focus on near objects –
i.e. difficulty reading – and is termed presbyopia. It can be corrected by either
glasses used exclusively for reading (i.e. reading glasses) or the lower segment
of glasses used for distance vision that contain increased power (i.e. the bifocal
segment).

Development of the Eye

The eye starts to develop in the fetus on day 22 following fertilization with
the appearance of the optic primordium in the neural folds. It continues
throughout fetal development and is completed in the 9th month with the devel-
opment of the peripheral retinal vessels, myelinization of the fibers of the optic
nerve and disappearance of the pupillary membrane [2, 3]. The embryonic tis-
sues of the eye are derived from ectoderm and mesoderm. The ectoderm gives
rise to the neuroectoderm (e.g. neurosensory retina and retinal pigment epithe-
lium), the neural crest cells (e.g. corneal stroma and endothelium, as well as
choroid) and the surface ectoderm (e.g. conjunctival epithelium, corneal epithe-
lium, and lens).
The embryonic and fetal development of the human eye involves a series of
sequential steps, including inductive interactions and the migration of cells from
distinct regions of the embryo. Three elements have been identified as important
in this process: growth factors, homeobox genes, and neural crest cells.
Growth factors are soluble molecules that provide the chemical signals in the
earliest stages of embryonic development. There are certain substances that par-
ticipate and control the normal development of the eye influencing the migration,
proliferation, and differentiation of cells. Fibroblast growth factor, transforming
growth factor-␤ and insulin-like growth factor-I are essential for the normal
development of the eye [4]. They not only provide signals for the differentiation
of cells in the region of the eye, but they also regulate the level of expression of
homeobox genes. These latter genes function as the mechanism for controlling
the overall arrangement of the eye as an organ. Visual acuity is dependent upon
the precise spatial arrangement of the cells of the eye. Therefore, the expression
of homeobox genes at the appropriate level and time are critical.
Homeobox genes contain a distinctive segment of DNA, 180 base pairs in
length, that encodes an almost identical sequence of 60 amino acids. Since
these genes control the activity of other subordinate genes, homeobox genes are
considered ‘master’ genes. These genes act as transcription factors and bond to
specific DNA sequences of subordinate genes, resulting in activation or repres-
sion of their expression. Thus, the spatial and temporal expression of homeobox
genes is critical to the normal embryonic development of the eye [5, 6].
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 The neuroectoderm located at the crest of the neural folds gives rise to the
neural crest cells. They migrate to different regions of the embryo where differ-
entiation occurs; therefore, they are a transient population of cells. The signals
these cells encounter during migration guide the cells along the correct pathway
to their appropriate destination. The secretion of extracellular matrix molecules
such as collagen, fibronectin, and proteoglycans is influenced by growth fac-
tors, which, thus, also have a role in regulating the migration of neural crest
cells. Early in development the neural crest cells are multipotent, but their final
differentiation is considerably influenced by local factors.

The Anatomy of the Eye

Immune privilege of the eye involves the globe and its contents. Thus, only a
passing reference will be made to the orbit and eyelids. The orbit is the bony, con-
cave cavity in the skull that houses the globe, extraocular muscles, blood vessels
and nerves of the eye. There is a very thin orbital floor (consisting of the maxillary,
palatine, and zygomatic bones), a medial wall (consisting of the frontal process of
the maxilla, lacrimal bone, orbital plate of the frontal bone, and lesser wing of the
sphenoid), an orbital roof (consisting of the frontal bone), and a lateral wall (con-
sisting of the zygomatic and greater wing of the sphenoid) (fig. 2) [8].
The globe is protected by the eyelids and lubrication of the ocular surface.
The upper and lower eyelids are comprised of skin, subcutaneous connective
tissue, and muscle. In addition, the tarsal plates in each lid consist of dense con-
nective tissue and cartilage. They contain the meibomian glands – modified
holocrine sebaceous glands – that are oriented vertically in two parallel rows
through the tarsus. Movement of the eyelids assists lubrication of the surface of
the globe, as well as protection from inadvertent trauma [9].
The surface of the cornea is protected by the tear film. It is a trilaminar layer
consisting of an anterior lipid layer, a middle aqueous phase, and a posterior
mucin layer [10]. The anterior layer of the tear film contains polar and
non-polar lipids secreted primarily by the meibomian (tarsal) glands. The seba-
ceous glands in the lid margin are in close relation to the eyelashes and also
secret lipids (fig. 3). The middle aqueous layer is secreted by the main and acces-
sory lacrimal glands. The main lacrimal gland is located in a shallow depression
within the orbital plate of the frontal bone. The accessory lacrimal glands of
Krause and Wolfring are located in the conjunctival fornices. The mucin layer of
the tear film coats the superficial corneal epithelial cells and conjunctival sur-
face. Tear mucins are secreted normally by the conjunctival goblet cells.
The thick outer coat of the eye, the sclera, is white and opaque. The trans-
parent front window of the eye, which serves as the major refractive surface, is
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 Frontal bone Supraorbital foramen

Greater wing
of sphenoid Superior orbital ridge

Superior orbital fissure

Inferior Optic foramen

orbital Lesser wing of
fissure sphenoid vone
Ethmoid

Lacrimal bone
and fossa

Zygomatic
Maxilla

Infraorbital foramen

Fig. 2. Frontal view of the bony right orbit (reproduced with permission of Lippincott
Williams & Wilkins [7]).

Fig. 3. Cross-section of the upper eyelid (reproduced with permission of Lippincott

Williams & Wilkins [3]).
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the cornea (fig. 1). Light rays pass through the cornea into the anterior chamber
which is filled with aqueous humor. The rays then continue as they pass through
the lens, the major internal refractive structure of the eye. The rays then enter
the clear vitreous cavity and impinge upon the neurosensory (neural) retina.
The pigmented epithelium of the retina (retinal pigment epithelium) provides
nourishment and support to the outer layers of the neurosensory retina – the
photoreceptors (rods and cones). Nourishment for the photoreceptors is derived
from the vessels within the choroid. The choroid extends anteriorly and with the
ciliary body and iris comprises the uveal tract of the eye.
As light passes through the inner retina it is absorbed by the photorecep-
tors in the neuorsensory retina. Light is either absorbed by rhodopsin, which is
concentrated in the outer segment membrane of rods, or by opsin, which is
located in cones. Phototransduction is the process by which light is captured by
the photoreceptors and the small amount of energy is converted into a neural
response. Through a series of biochemical reactions in the neural retina, the
ganglion cells are depolarized and transmit a visual signal to the lateral genicu-
late nucleus of the central nervous system [11].

Anatomy of Immune Privilege

Immune privilege within the eye is dependent upon many molecular bio-
chemical interactions, as well as novel anatomic features – e.g. the alymphatic sta-
tus of the internal structures of the eye and the blood ocular barrier. The
conjunctiva is a mucous membrane consisting of non-keratinized squamous
epithelium with numerous goblet cells and a rich vascularized substantia propria.
The latter contains lymphatic vessels as well as bone-marrow-derived inflamma-
tory cells. Specialized aggregations of conjunctiva-associated lymphoid tissue
(CALT) are present and thought to be analogous to mucosa-associated lymphoid
tissue (MALT), which is present in the intestine. These aggregations are comprised
of T and B lymphocytes, as well as antigen-presenting cells and epithelium [12].
The fluid compartments of the eye (aqueous humor and vitreous) are sepa-
rated from blood by various tight junctions (zonulae occludens) between
endothelial or epithelial cells. The capillaries of the retinal vascular circulation
(i.e. endothelium), as well as the interdigitating surfaces of the retinal pigment
epithelium and non-pigmented epithelium of the ciliary processes, contain
zonulae occludens [13]. They constitute an effective barrier to soluble mole-
cules and contribute to the novel constitution of the aqueous humor and vitre-
ous. Both the alymphatic status of the inner globe and the blood ocular barrier
have been postulated to be important anatomical contributions to the existence
of immune privilege. In various diseases the blood ocular barrier is disrupted
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and associated with the loss of immune privilege within the eye. The presence
of collateral lymphatic channels within the normal eye, as well as during dis-
ease, has been postulated but remains an unresolved issue to date [14, 15].

References

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11 Retina; in Basic and Clinical Science Course; Section 2: Fundamentals and Principles of
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12 Knop N, Knop E: Conjunctiva-associated lymphoid tissue in the human eye. Invest Ophthalmol
Vis Sci 2000;41:1270–1279.
13 Kaufman PL, Alm A: Adler’s Physiology of the Eye, ed 10, revised. St. Louis, Mosby, 2003.
14 Junghans BM, Wadley RB, Crewther SG, Crewther DP: X-ray elemental analysis differentiates
blood vessels and lymphatic vessels in the chick choroids. Aust NZ J Ophthalmol 1999;27:244–246.
15 Liang H, Crewther SG, Crewther DP, Junghans BM: Structural and elemental evidence for edema
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Dr. Henry J. Kaplan

Department of Ophthalmology and Visual Science, University of Louisville
301 East Muhammad Ali Boulevard
Louisville, KY 40202 (USA)
Tel. ⫹1 502 852 5466, Fax ⫹1 502 852 4595, E-Mail hank.kaplan@louisville.edu
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