10. Eye.

Tunica Fibrosa

a) The tunica fibrosa is composed of the sclera and the cornea. The external
fibrous tunic of the eye, the tunica fibrosa, is divided into the sclera and the
cornea. The white, opaque sclera covers the posterior five sixths of the
eyeball, whereas the colourless, transparent cornea covers the anterior one
sixth of the eyeball.

b) Sclera –

the white of the eye, is nearly devoid of blood vessels. It is a tough fibrous connective
tissue layer that covers approximately 85% of the eyeball. It is about 1 mm thick
posteriorly, thinning at the equator and then thickening again near its junction with the
cornea. It consists of interlacing type I collagen fiber bundles alternating with
networks of elastic fibers; this arrangement gives form to the eyeball, which is
maintained by intraocular pressure from the aqueous humor (located anterior to the
lens) and the vitreous body (located posterior to the lens).

Fibroblasts of the sclera are elongated, flat cells. Melanocytes are located in deeper
regions of the sclera. Tendons of the extraocular muscles insert into the dense
connective tissue surface layer of the sclera, which is enveloped by the capsule of
Tenon, a fascial sheath that covers the optic nerve and the eyeball as far anteriorly as
the ciliary region. This sheath, which separates the eye from the periorbital fat, is
connected to the sclera by a thin layer of loose connective tissue called the episclera.
The eyeball, along with its various parts and attached extraocular muscles, moves in
unison within the periorbital fat–filled bony orbit.

c) Cornea –

The cornea is the transparent, avascular, and highly innervated anterior portion of the
fibrous tunic that bulges out anteriorly from the eyeball. It is slightly thicker than the
sclera and is composed of six histologically distinct layer, Corneal epithelium,
Bowman membrane, Stroma, Pre-Descemet layer (Dua layer), Descemet membrane
and Corneal endothelium.
Corneal epithelium, the continuation of the conjunctiva, is a stratified, squamous,
nonkeratinized epithelium, composed of five to seven layers of cells, that covers the
anterior surface of the cornea. The larger superficial cells have microvilli and exhibit
zonulae occludentes. The remaining cells constituting the corneal epithelium
interdigitate with and form desmosomal contacts with one another. Damage to the
cornea is repaired rapidly as cells migrate to the defect to cover the injured region.
Subsequently, mitotic activity replaces the cells that migrated to the wound. The
corneal epithelium also functions in transferring water and ions from the stroma into
the conjunctival sac.

Bowman membrane lies immediately deep to the corneal epithelium Sensory nerve
fibers pass through this structure to enter and terminate in the epithelium. The
transparent stroma is the thickest layer of the cornea, constituting about 90% of its
thickness. The collagen fibers within each lamella are arranged parallel to one
another, but fiber orientation shifts in adjacent lamellae. The collagen fibers are
interspersed with thin elastic fibers, embedded in ground substance containing mostly
chondroitin sulfate and keratan sulfate. During inflammation, lymphocytes and
neutrophils are also present in the stroma. At the limbus (sclerocorneal junction) is a
scleral sulcus whose inner aspect at the stroma is depressed and houses endothelium-
lined spaces, known as the trabecular meshwork, that lead to the canal of Schlemm.
The canal of Schlemm is the site of outflow of the aqueous humor from the anterior
chamber of the eye into the venous system.

Pre-Descemet layer (Dua layer) is a 15-µm, thin, tough collagenous membrane that is
probably manufactured by the fibroblasts of the stroma. It has been suggested that the
durability of this recently discovered layer protects the cornea from damage, whereas
physical injury that breaches the integrity of pre-Descemet layer may result in corneal
hydrops (infiltration of an aqueous fluid into the corneal stroma).

Descemet membrane is a thick basement membrane interposed between the stroma

and the underlying endothelium. Although this membrane is thin (5 µm at birth) and
homogeneous in younger persons, electron microscopy has demonstrated that it
becomes thicker (17 µm) and has cross-striations and hexagonal fiber patterns in older
adults.
 The corneal endothelium, which lines the internal (posterior) surface of the cornea, is
a simple squamous epithelium. It is responsible for synthesis of proteins that are
necessary for secreting and maintaining Descemet membrane. These cells exhibit
numerous pinocytotic vesicles, and their membranes have sodium pumps that
transport sodium ions (Na+ ) into the anterior chamber. Thus, excess fluid within the
stroma is resorbed by the endothelium, keeping the stroma relatively dehydrated, a
factor that contributes to maintaining the refractive quality of the cornea.

11. Tunica Vasculosa

a) The vascular middle tunic of the eye, the tunica vasculosa (uvea), is composed of
three parts: (1) the choroid, (2) the ciliary body, and (3) the iris.

b) Choroid - The choroid, the well-vascularized, pigmented layer of the posterior

wall of the eyeball, is loosely attached to the tunica fibrosa. It is composed of
loose connective tissue containing numerous fibroblasts and other connective
tissue cells, and it is richly supplied with blood vessels. The black colour of the
choroid is due to the myriad of melanocytes present in it. Because of the
abundance of small blood vessels in the inner surface of the choroid, that region is
known as the choriocapillary layer and is responsible for providing nutrients to the
retina. The outer aspect of each collagen fiber layer is covered by a basal lamina
that belongs to capillaries on one side and the pigment epithelium of the retina on
the other side.

Ciliary Body - the wedge-shaped extension of the choroid that rings the inner wall
of the eye at the level of the lens, occupies the space between the ora serrata of the
retina and the iris. The ciliary body is composed of loose connective tissue
containing numerous elastic fibers, blood vessels, and melanocytes. The ciliary
processes are covered by the same two layers of epithelia that cover the ciliary
body. The inner nonpigmented layer has many interdigitations and infoldings; its
cells transport a protein-poor plasma filtrate, the aqueous humor, into the posterior
chamber of the eye. The aqueous humor flows from the posterior chamber into the
anterior chamber by passing through the pupillary aperture between the iris and
 the lens. The aqueous humor exits the anterior chamber by passing into the
trabecular meshwork near the limbus and, finally, as stated above, into the canal
of Schlemm, which leads directly into the venous system. The aqueous humor
provides nutrients and oxygen for the lens and the cornea.

c) Iris - the anteriormost extension of the choroid, lies between the posterior and
anterior chambers of the eye, completely covering the lens except at the pupillary
aperture (pupil). The iris is thickest in the middle, thinning both toward its
junction with the ciliary body and at the rim of the pupil. The anterior surface
consists of two concentric rings. An incomplete layer of pigmented cells and
fibroblasts covers the anterior surface of the iris. Deep to this layer is a stroma of
poorly vascularized connective tissue containing numerous fibroblasts and
melanocytes, which gives way to a well-vascularized, loose connective tissue
zone. The posterior surface of the iris is smooth and is covered by the continuation
of the two layers of retinal epithelium that cover the ciliary body. The surface
facing the lens is composed of heavily pigmented cells, which block the light from
passing through the iris except at the pupil. The epithelial cells facing the stroma
of the iris have extensions that form the dilator pupillae muscle. The sphincter
pupillae muscle, is located in a concentric ring around the pupil. Contractions of
these smooth muscles alter the diameter of the pupil. The diameter of the pupil
changes inversely with the amount of light entering it. Pupil diameter is the result
of the functions of the two intrinsic muscles contained within the iris. As their
names imply, the dilator pupillae muscle, innervated by the sympathetic nervous
system, dilates the pupil; whereas the sphincter pupillae muscle, innervated by
parasympathetic fibers of the oculomotor nerve (CN III), constricts the pupil.

12. Lens

a) The lens of the eye is a flexible, biconvex, transparent disk composed of epithelial
cells and their secretory products. The lens consists of three parts: lens capsule,
subcapsular epithelium, and lens fibers. The lens capsule is a basal lamina,
containing mostly type IV collagen and glycoprotein that covers the epithelial
cells and envelops the entire lens. This elastic, transparent, homogeneous
structure, which refracts light, is thickest anteriorly. The subcapsular epithelium is
 located only on the anterior and lateral surfaces of the lens, immediately deep to
the lens capsule. It is composed of a single layer of cuboidal cells, which
communicate with each other via gap junctions. The apices of these cells are
directed toward the lens fibers and interdigitate with them, especially in the
vicinity of the equator, where they are elongated and are columnar in shape. The
lens maintains its location in the eyeball by the presence of the suspensory
ligaments that are attached to the ciliary muscles. When these muscles are in the
contracted state, there is little tension on the ligaments, and the lens is more
convex so that near vision is sharper; whereas, during the relaxation of the ciliary
muscles, the tension on the ligaments is increased, making the lens flatter and
distant vision is sharp.

b) Vitreous Body - is a transparent, refractile gel that fills the cavity of the eye
(vitreous cavity) behind the lens. It is composed mostly (99%) of water containing
a minute mount of electrolytes, collagen fibers, and hyaluronic acid. It adheres to
the retina over its entire surface, especially at the ora serrata. The fluidfilled
hyaloid canal, a narrow channel that was occupied by the hyaloid artery in the
fetus, extends through the entire vitreous body from the posterior aspect of the
lens to the optic disk.

13. Retina

a) The retina, the third and innermost tunic of the eye, is its neural portion, which
contains the photoreceptor cells, known as rods and cones. The retina develops
from the optic cup, an evagination of the diencephalon, which gives rise to the
primary optic vesicle. Later in development, this structure invaginates to form a
bilaminar secondary optic vesicle from which the retina develops, whereas the
stalk of the optic cup becomes the optic nerve. The retina is formed of an outer
pigmented layer that develops from the outer wall of the optic cup. The neural
portion of the retina develops from the inner layer of the optic cup and is called
the retina proper. The pigmented layer of the retina covers the entire internal
surface of the eyeball, reflecting over the ciliary body and the posterior wall of the
iris, whereas the retina proper stops at the ora serrata. The cells composing the
retina proper constitute a highly differentiated extension of the brain. The optic
disk, located on the posterior wall of the eyeball, is the exit site of the optic nerve.
Because it contains no photoreceptor cells, it is insensitive to light and is therefore
called the blind spot of the retina. The optic disk is a yellow-pigmented zone in
the retinal wall called the macula lutea (yellow spot). Located in the center of this
spot is an oval depression, the fovea centralis, where visual acuity is greatest. The
retina has a dual blood supply. Much of the internal layers of the retina, from the
internal segments of the rods and cones through the optic nerve fiber layer, is
supplied by the central retinal artery, which gains access to the eyeball via the
center of the optic nerve and forms numerous branches on the surface of the
internal aspect of the retina. The external layers of the retina that constitute the
outer segments of the rods and cones and the pigment epithelium are served by the
vascular supply of the choroid.

Layers of Retina - From outside, adjacent to the choroid, to inside, where the
vitreous humor abuts the retina, there are 10 layers. Pigment epithelium, Layer of
rods and cones, Outer limiting membrane, Outer nuclear layer, Outer plexiform
layer, Inner nuclear layer, Inner plexiform layer, Ganglion cell layer, Optic nerve
fiber layer and Inner limiting membrane.

Pigment Epithelium - The pigment epithelium, derived from the outer layer of the
optic cup, is composed of cuboidal to columnar cells whose nuclei are located
basally. The cells are attached to Bruch membrane, which is located between the
choroid and the pigment cells. Mitochondria are especially abundant in the
cytoplasm near the numerous cell invaginations with Bruch membrane, suggesting
transport in this region. Desmosomes, zonulae occludentes, and zonulae
adherentes are present on the lateral cell membranes, forming the blood–retina
barrier. The pigmented epithelium has several functions. Pigmented epithelial
cells absorb light after it has passed through and stimulated the photoreceptors,
thus preventing reflections from the tunics, which would impair focus. These
pigmented cells continually phagocytose spent membranous disks from the tips of
the photoreceptor rods and cones. Pigment epithelial cells also play an active role
in vision by esterifying vitamin A derivatives in their smooth endoplasmic
reticulum and by storing vitamin A in their cytoplasm and releasing it to the rods
and cones as needed.
14. Rods and Cones

a) Rods, which are activated in dim light only, are so sensitive that they can produce
a signal from a single photon of light. However, they cannot mediate signals in
bright light, and they cannot sense colour. Rods are elongated cells oriented
parallel to one another but perpendicular to the retina. These cells are composed of
an outer segment, an inner segment, a nuclear region, and a synaptic region. The
outer segment of the rod, its dendritic end, presents close to a thousand flattened
membranous lamellae oriented perpendicular to its long axis. The membranes
contain a specific form of the light sensitive pigments opsins, known as rhodopsin
(visual purple). Because the outer segment is longer in rods than in cones, rods
contain more rhodopsin, respond more slowly than cones, and have the capacity to
collectively summate the reception. The cell membrane of the outer segment
houses cyclic guanosine monophosphate (cGMP)–gated Na+ ion channels that are
kept open by the cGMP that are bound to the gates if there are no photons
impinging on the rod, that is, if it is dark. Therefore, in the dark, Na+ ions may
enter the outer segment of the rod.

b) Cones, are specialized photoreceptors of the retina for perceiving bright light and
color. There are three types of cones, L cones (long wavelength), M cones
(medium wavelength), and S cones (short wavelength), each containing a different
variety of the photopigment opsin, known as photopsin and responding to
different wavelengths of light. Cones are elongated cells being longer and
narrower at the fovea centralis. Their structure is similar to that of rods, for
example, their apical terminal (outer segment) is shaped more like a cone than a
rod. The disks of cones, although composed of lamellae of the plasmalemma, are
attached to the plasma membrane, unlike the lamellae of the rods, which are
separated from the plasma membrane. Protein produced in the inner segment of
cones is inserted into the disks throughout the entire outer segment; in the rods, it
is concentrated in the most distal region of the outer segment. Unlike rods, cones
 are sensitive to color and provide greater visual acuity. Recycling of the cone
photopigment does not require the retina pigment cells for the processing. Cones
are not nearly as sensitive (as much as 100 times less sensitive) to light than rods,
but they are still able to discriminate color at relatively poorly lit conditions. The
synaptic vesicles housed in the synaptic region of cones, just as in rods, contain
the neurotransmitter substance glutamate, which they release into the synaptic
cleft when they become hyperpolarized.

15. Layer of Retina : Inner Nuclear Layer.

a) The nuclei of bipolar, horizontal, amacrine, and Müller cells compose the inner
nuclear layer. Bipolar neurons are interposed between photoreceptor cells and
ganglion cells. These neurons may be contacted by many rods, permitting
summation of the signals, which is especially useful in low light intensity. There
are two types of bipolar neurons, those that become depolarized upon being
stimulated by the glutamine released by rods or cones and those that become
hyperpolarized when stimulated by glutamine released by rods or cones. It is
believed that the two types of cells assist in enhancing visual contrast.
Horizontal cells located in this layer synapse with the synaptic junctions between
the photoreceptor cells and the bipolar cells. As their name implies, these cells
transmit information in a horizontal plane only from rods and cones to bipolar
cells. These cells enhance visual contrast by permitting the transmission of
impulses from bipolar cells that have been excited in the immediate vicinity of
cones and rods that are hyperpolarized but inhibit the transmission of impulses by
bipolar cells peripheral to the area of light impingement, a mechanism known as
lateral inhibition.

Amacrine cells are located at the inner limits of this layer. They synapse on
interproximal cells that are interspersed with bipolar cell bodies. There are many
different types of amacrine cells, some that synapse with bipolar cells and
ganglion cells, or with bipolar cells and other amacrine cells. Amacrine cells
appear to function as interneurons that control whether or not a visual information
should be transmitted to the visual center of the brain.
 Müller cells are neuroglial cells that extend between the vitreous body and the
inner segments of the rods and cones. Müller cells function as supporting cells for
the neural retina. This support is twofold, namely physical/physiological and as
light conducting. Physical or physiological support. Involves maintaining the
proper relationships among the cells of the retina, regulating the extracellular ion
levels, neurotransmitter levels, and insulating the various cellular components of
the retina. Secondly, Light conducting support. Involves the separation of the
various wavelengths of light and guiding of the impinging photons of correct
wavelength to the rods and cones that are designed for their maximal reception.
Therefore, Muller cells appear to act as if they were wavelength-specific fiber
optic cables.

16. Layer of Retina : Ganglion Cell Layer

a) Cell bodies of large multipolar neurons of the ganglion, are located in the ganglion
cell layer. Hyperpolarization of the rods and cones indirectly activates these
ganglion cells, which then generate an action potential that is passed by their
axons to the brain via the visual relay system. There are four types of ganglion
cells: W cells, X cells, Y cells dedicated to vision, and the photosensitive retinal
glial cells dedicated to relay information to the pineal gland, informing that
structure whether it is day or night and regulating the pupillary reflex.

W ganglion cells. Smallest, with a cell body and slowest with a conduction
velocity. The amacrine and bipolar cells that synapse with W cells convey
information mostly from rods and they are responsible for much of the night
vision.

X ganglion cells. These cells are responsible for most of the color vision because
they receive information from amacrine and bipolar cells that synapse with cones.
Each X cell receives information from a small region of the retina, therefore, they
provide information that is specific for location of the visual event.
Y ganglion cells. Larger and relay information faster than W or X cells. They
receive information from bipolar and amacrine cells from large areas of the visual
field. They are responsible for monitoring changes in the entire visual field but do
not provide precise information concerning the location of visual event.

Photosensitive retinal glial cells. These cells possess a photopigment, similar to

the opsins of the rods and cones, known as melanopsin. When PSRGCs are
exposed to light, they send information to these regions indicating that presence of
light; when they do not send information, it indicates that it is dark. PSRGCs also
receive input from amacrine cells and bipolar cells that synapse with rods and
cones, providing a redundancy, thus ensuring that regions of the brain that
establish the circadian rhythm receive pertinent information about daylight and
dark. These cells are also responsible for the pupillary reflex, whereby the pupil
opens or closes depending on the amount of light impinging on the retina.