The tear film has three layers: 1. A mucin layer secreted by goblet cells that forms a hydrophilic barrier on the cornea. 2. An aqueous layer secreted mainly by the lacrimal gland, containing proteins, electrolytes, and other components. 3. An outer lipid layer secreted by meibomian glands that prevents evaporation and maintains tear film stability. The tear film is regulated by hormonal and neural pathways and provides nutrients to the cornea, removes waste, lubricates the eye, and protects against infection through its biochemical composition.

1. Ocular Biochemistry
Unit 3

2. Tear film
Unit 3
Formation and regulation (Hormonal and
Nerves control), Layers, Structure, Biochemical
composition, stability, functions and
abnormalities. Changes in contact lens wearer

3. Tear Film

4. Tear Film
Functions: Nourishment of cornea
• transport metabolites to, and remove waste products from the
epithelial cells of the cornea
• Since the corneal lack a blood supply, they must be provided
with oxygen and nutrients.
• Carbon dioxide and metabolic waste products must also be
removed.
• The nearest blood supply to the cornea is at the limbus, which
connects the cornea to the adjacent sclera. The limbal and
conjunctival blood vessels provide for these needs by supplying
a small amount of O2 and small nutrient molecules to the
cornea and removing CO2.

5. Tear Film
Functions
• When the eye is open, tears secreted from the orbital glands provide the bulk of O2
and nutrients in their secretions and remove CO2
• When the eye is closed, the aqueous humor, which bathes the endothelial side of
the cornea, supplies the cornea with its entire metabolic needs.
It is interesting to note that differentiated (multiple‐cell layered) corneas survive best in
culture when they are placed at the air–fluid interface and not submerged . This suggests
that the unique ocular surface/air interaction is important to the structure and function of
the cornea.

6. Tear Film
Functions: pH and Osmolality
• to provide the entire ocular surface with a moist environment with the
appropriate electrolyte composition. The ocular surface has a narrow range
of pH, osmolarity, and ionic concentrations necessary for optimal function.
Small changes in these variables, especially osmolarity and ion
concentrations lead to ocular surface
• Tear pH is maintained between 7.14 and 7.82 by the buffers in the eye that
are mainly bicarbonate (HCO3 - ), H + , and proteins (H + acceptors).

7. Tear Film
Functions: pH and Osmolality
• Tear osmolarity is normally 300–304 mOsm and is similar to that of plasma
• An increase of 10 mOsm is enough to be deleterious to the ocular surface,
especially the conjunctiva
• Tear osmolarity is derived from the ionic composition of tears, which is unique
when compared to plasma or other body fluids. Tears contain Na + , K + , Cl-, HCO3 -
, Ca2+ , Mg2+ , and trace levels of other ions
• Tears have a higher K + and Cl- concentration and a similar Na + concentration
compared to plasma

8. Tear Film
Functions: pH and Osmolality
• This implies that tears are not an ultrafiltrate of plasma, but are secreted by
the orbital glands
• Because this secretion is highly regulated, the ionic composition of tears
(thus the osmolarity and pH) can be tightly controlled and the health of the
ocular surface maintained

9. Tear Film
Functions: Protein composition
• Protein composition is also important for a healthy ocular surface
• Tears contain a large number of proteins, which are secreted by the orbital glands
• Tears do not normally contain serum proteins, although these can enter the
tears from leaky conjunctival blood vessels under pathological conditions
• One of the most important functions of tear proteins is preventing bacterial and
viral infections. The major tear proteins, lysozyme, secretory immunoglobulin (IgA),
lactoferrin, lipocalin, and peroxidase are antibacterial

10. Tear Film
Functions: Protein composition
• The high‐molecular weight glycoproteins in tears known as mucins are also antibacterial
and antiviral. Mucins are secreted onto the ocular surface and protect the underlying
epithelial cells by binding to and entrapping bacteria and viruses
• The carbohydrate side chains of mucins, which are attached to the protein core, are able
to bind to a wide variety of pathogens
• Since each type of pathogen has a specific carbohydrate sequence to which it will bind,
mucin carbohydrate side chains are heterogeneous and are able to bind a wide variety of
microorganisms.

11. Tear Film
Functions: Protein composition
• When mucins bind to bacteria or viruses, they prevent them from attaching to the
ocular surface and invading it
• Thus, mucins block microbial binding sites before the microorganism penetrates
the ocular surface and prevent infection
• functions include cellular migration and proliferation during wound repair, normal
cellular differentiation, and secretion of electrolytes and water
• Tears contain a wide variety of growth factors, cytokines and biologically active
peptides

12. Tear Film
Functions: protection of eye
• Tears protect the eye from noxious stimuli, such as acids, bases, and other
chemicals. Tears also remove particles and debris, such as eyelashes or makeup,
from the ocular surface
• Two components of tears are effective in this mechanism. External irritants of the
ocular surface cause neutrally mediated reflex secretion of water and electrolytes
to neutralize and wash away the irritants
• The same neural pathways also stimulate mucin secretion.

13. Tear Film
Functions: protection of eye
• Mucins physically entrap and remove irritants.
• As the cornea and conjunctiva are innervated with sensory nerves, reflex secretion of
electrolytes, water, and mucins provide a rapid response to noxious stimuli
• The blinking mechanism then washes irritants into the lacrimal drainage system
effectively removing them from the ocular surface.

14. Tear Film
Functions
• Form a smooth optical surface by filling irregularities of
corneal epithelium
• Keeps the cornea and conjuctiva moist
• Serves as a lubricant for lids
• Transfer air to the cornea
• Prevent infections
• Washes away debris and irritants
• Provides pathway to WBC in case of injury

15. Tear Film: Glands Involved
The trilaminar tear film originates from three sources.
1. The lacrimal glands secrete a variety of water-soluble substances that comprise the intermediate tear
film layer: these include electrolytes, proteins, retinol, immunoglobulins, and enzymes
2. The thin anterior lipid layer, which contains both polar and nonpolar lipids, is secreted by the
meibomian glands
3. The inner mucous layer is secreted mainly, if not entirely, by the conjunctival goblet cells
There are, however, reports that small amounts of mucus layer may also be derived from the lacrimal
gland acinar cells and from subsurface secretory vesicles of the conjunctival and corneal epithelium

16. The lacrimal glands
Tear Film: Glands Involved
the lacrimal glands are paired, almond-shaped
exocrine glands, one for each eye, that secrete
the aqueous layer of the tear film. They are
situated in the upper lateral region of each
orbit, in the lacrimal fossa of the orbit formed
by the frontal bone.

17. the meibomian glands
Tear Film: Glands Involved
Meibomian glands (often written with a small "m" and also called tarsal
glands) are holocrine type exocrine glands, along the rims of the eyelid
inside the tarsal plate. They produce meibum, an oily substance that
prevents evaporation of the eye's tear film.

18. conjunctival goblet cells
Tear Film: Glands Involved
Goblet cells are highly specialized epithelial cells,
present in mucosal tissues along the body. The main
function of these cells is to produce and secrete
mucins, which hydrate and lubricate mucosal surfaces.
Under non-pathologic conditions in the eye, goblet
cells are confined to the conjunctival epithelium

19. Glands of zeis and Gland of moll
Tear Film: Glands Involved
Glands of Zeis are unilobar sebaceous glands
located on the margin of the eyelid. The
glands of Zeis service the eyelash. These
glands produce an oily substance that is
issued through the excretory ducts of the
sebaceous lobule into the middle portion of
the hair follicle. In the same area of the eyelid,
near the base of the eyelashes are apocrine
glands called the "glands of Moll".

20. Glands of zeis and Gland of moll
Tear Film: Glands Involved
Krause's glands are small, mucous accessory
lacrimal glands that are found underneath the
eyelid where the upper and lower conjunctivae
meet. The function of these glands are to
produce tears which are secreted onto the
surface of the conjuctiva

21. Glands of zeis and Gland of moll
Tear Film: Glands Involved
Wolfring's glands are small tubular accessory
lacrimal glands (glandulae lacrimales
accessoriae) found in the lacrimal caruncle of
the eyelid. They are located in the upper border
of the tarsus, approximately in the middle
between the extremities of the tarsal glands.

22. Tear Film
Structure
Epithelium
Glycocalyx
Lipid
Lipid layer
(0.1 μm)
Aqueous Layer
(8 μm)
Mucin Layer
(0.02 – 0.05 μm)
Membrane spanning mucin
Cleaved Membrane spanning mucin
Gel-forming mucin

23. Tear Film

24. 3 LIPID LAYER
• Outer most oily layer, derived from Meibomian glands, glands of Ziess and
glands of Moll
• Contains lipids with low polarity such as wax and cholesterol esters
• Fluid layer, 10 μm
• Formed from polar and neutral lipid face aqueous component of tear film and
non polar lipids face the air
• Triglycerides, FFA, phospholipids are present in low amounts

25. 3 LIPID LAYER
Functions of lipid layer include
• Oily layer of tear film prevents the over flow of tears and retards their
evaporation. The latter fact accrues from the observation that cauterization of
the orifices of meibomian glands increases the evaporation by more than 10
times and results in absence of oily layer.
• It prevents migration of skin lipids onto the ocular surface
• It provides a clear ocular medium and smooth surface for refraction of light

26. 3 LIPID LAYER
Functions of lipid layer include
• Acts as a barrier for preventing contamination of tear film
• It acts as a surfactant layer which makes an effective bridge between the non-
polar lipid phase and aqueous-mucinous phase
• It acts as a lubricant to facilitate smooth movement of eyelids during blinking

27. 2 AQUEOUS LAYER
• The middle layer and the main bulk of tear film
• Secreted by lacrinal glands and accessory glands
of Krause and Wolfring
• 60% of the tear film
• Aqueous solution of low viscosity, containing
ions of organic salts, glucose, urea, enzymes,
tear specific prealbumin and secretory Ig-A

28. 2 AQUEOUS LAYER
• Because of bicarbonate and protein give a buffering capacity to this layer
• Electrolyte concentration in this layer varies with flow rate. At low flow rates
the layer is hypertonic where as at high flow rates it becomes isotonic
• They form the basal tear or normal lacrimation
• Reflex tears are the result of excessive lacrimation from lacrimal gland
• 7 μm, It forms a uniform layer

29. 2 AQUEOUS LAYER
• Lysozyme, lactoferin, tear specific prealbumin and immunoglobulin A
• Macromolecular mucous glycoproteins determine the surface tension of fluid
Functions of aqueous layer include
• Provides atmospheric O2 to epithelium
• Washes away debris and irritants
• Contain antibacterial substances like lysozyme and betalysin
• It has antibacterial, antiadhesive and lubricant properties

30. 1 MUCIN LAYER
• Deepest layer, 0.02-0.04 μm
• Secreted by conjunctival goblet cells, crypts of Henle, gland of Manz and also by main
Lacrinal gland
• Mucus layer is made of epithelial cell glycocalyx and a layer of tear mucin (glycoprotein)
• MUC5AC is the main tear mucin which is produced along with trefoil protein TFF1 and 3
• Made of glycoprotein, mixed with lipids, anchored by micro villi
• Clear corneal epithelium is a relatively hydrophobic surface. In order for tears to completely
cover cornea the surface must be converted to a hydrophilic surface.

31. 1 MUCIN LAYER
Glycocalyx
• long chain molecules that help hold mucin to the corneal surface
• Formed by corneal cells, glycocalyx migrate out from the surface of the corneal microvilli to
form a hydrophilic network that holds mucin on the ocular surface
• Holding mucin to the ocular surface creates a water attraction, as well as protection against
bacterial pathogens

32. 1 MUCIN LAYER
Glycoprotein/mucin
• produced by goblet cells, mixed and spread by action of lids, gets adsorbed on the cell
membrane of epithelial cells and anchored by their microvilli forming a new hydrophilic
surface on which aqueous and lipid bilayer spread spontaneously
• It thus plays a vital role in the stability of pre ocular tear film, as the latter depends upon the
constant supply of mucin to maintain proper hydration of ocular surface tissues.

33. 1 MUCIN LAYER
Other functions
• Slippery coating over foreign bodies and protecting cornea and conjuctiva against abrasive
effects of particles as they move about with blinking
• It helps to retain the aqueous layer
• Mucous or glycoproteins have a polar and non polar end. The non polar end aligns with the
hydrophobic epithelial cells and the polar end attracts water
• Stabilizes tear film, Semisolid state, highly hydrated
• Lubricates ocular and palpebral surfaces and reduces friction

34. Tear Film
Chemical composition
Water
• Major component, 98.2%
• With salts dissolved Na+, K+, Cl-, HCO3-, Ca2+
Proteins
• Un-stimulated tears: 2gm/100ml
• Stimulated tears: 0.3-0.7 gm/100ml
• Group A: 15% of proteins, IgG, Albumin,Transferrin, Alpha-1 antitrypsin, Alpha1-antichymotripsin,
beta-2-microglobulins.
• Group B: synthesized by tear glands, also known as rapid migrating proteins. Lysozyme, IgA
Albumin
Tear specific protein (prealbumin)
• Acidic protein, exact function is unknown, might be stabilizing thin tear film

35. Tear Film
Chemical composition
Immunoglobulins
• IgA is most prominent
• Produced by plasma cells in conjuctiva
• defense against viral or bacterial antigens.
• IgM and IgE are also found.
Lysozyme
• a proteolytic enzyme, net positive charge
• Produced by acinar cells of lacrinal gland
• work against bacterial infections
• lysis of bacterial cell wall
Glycolytic enzymes, lactate dehydrogenase
Betalysin: antibacterial agent
Mucopoly saccharides
Glycoproteins
Amino acids
Lipids
Metabolites: glucose, lactate, pyruvate, urea
Electrolytes: Na+, K+, Ca2+

36. Regulation
regulatory systems are of major influence of the differentiation and function
of the ocular surface
• The Nervous System
• The Endocrine Hormonal System
When the regulatory systems fail ... this leads to onset of basic underlying
factors for ocular surface disease

37. Nervous Regulation
• The ocular surface organs are
linked to neural reflex arc via
the afferent sensory cranial
nerve V (trigeminal) and via
the efferent motor fibers of
the cranial nerve VII (facial)
• SSN – Superior salivatory
nucleus

38. Nervous Regulation
• The reflex arcs typically link peripheral sensors at the ocular surface, which
are either special receptors or simply free nerve endings, via the regulatory
center of the brain stem, to efferent structures
• Efferent structures can ´respond´ a suitable answer that changes the
information of the sensors - typically by improving an unsuitable situation in
the periphery – back to the normal expected input.

39. Neural pathways from the sphenopalatine ganglion (SPG) and superior cervical ganglion
(SCG) control meibomian glands, lacrimal gland, and goblet cells
Nervous Regulation

40. Nervous Regulation
• The ocular surface organs are connected via nerves to the brain stem
• Neural Reflex Arcs between sensory nerves (typically trigeminal) and motor
nerves (typically facial) regulate functions such as tear secretion or blinking
• Here, blinking is triggered by a break-up of the tear film that leads to
irritation of corneal sensory nerves

41. Nervous Regulation
• A stimulus such as an irritation of epithelial cells and eventually of nerve
fibers, by e.g. dryness, mechanical friction and wounding, hyper-osmolarity,
temperature, wind or touch, is sensed and typically a respective answer is
triggered in the brain stem in order to evoke responses that ‘solve the
problem´
• increased glandular secretion or it can be an innervation of the lid muscle in
order to trigger blinking, either for a protective eye closure or as a means to
renew the tear film.

42. Nervous Regulation
• Eye closure, blinking and secretion are closely related and when the ocular
surface is accidentally touched this typically results in eye closure and
tearing, probably followed by blinking

43. Pain is another function of the nervous system
• The NERVOUS SYSTEM is connected via afferent nerves (here interrupted
blue lines) from the Ocular Surface and efferent fibers (here solid green
lines) to the Peripheral Organs
• Both fiber types have their center in the regulatory unit of the Brain Stem of
the Central Nervous System
• Functions of the Nervous System are not only the REGULATION of the tissue
function in a neural reflex arcs via the cranial nerves V (trigeminal) and VII
(facial) but also the Perception of Neural Sensations and of Feelings of PAIN.

44. Pain is another function of the nervous system
• Sensations mean that a stimulus comes into consciousness and is thus realized as
a basically neutral information
• The region for conscious realization of such external stimuli is the cortex - the
outer grey layer of the brain
• Pain, in contrast, is not a ´simple´ incoming neural sensation but is typically
associated with an emotional feelings that are typically negative
• A well known system associated with emotionalism is the limbic system that
forms a circular arrangement of different structures that are all involved in
emotions

45. Painisanotherfunctionofthenervoussystem

46. Neural control of the tear film.
1. Neural pathways from the sphenopalatine ganglion (SPG) and superior cervical ganglion (SCG) control
meibomian glands, lacrimal gland, and goblet cells
2. The trigeminal V1 (fifth cranial) nerve bears the sensory pathway (afferent) of the tear reflexes
3. The motor pathway is autonomic (involuntary), &, in general, uses the pathway of the facial (seventh)
nerve in the parasympathetic division via pterygopalatine/ spheno palatine ganglion, as efferent
pathway
A newborn infant has insufficient development of nervous control, so
she/he "cries without weeping”
Secretion of Tears: Neural control of the tear film.

47. Neural pathways from
the sphenopalatine
ganglion (SPG) and
superior cervical
ganglion (SCG) control
meibomian glands,
lacrimal gland, and
goblet cells
Nervous Regulation

48. Neural pathways from the sphenopalatine ganglion (SPG) and superior cervical ganglion
(SCG) control meibomian glands, lacrimal gland, and goblet cells
Secretion of Tears: Neural control of the tear film.

49. The endocrine system of hormones
• The organs of the ocular surface are all connected to the endocrine system of hormones
• This concerns the circulation of hormones and hormone precursors in the blood stream
that are of major influence for the growth, differentiation and functional regulation of
the ocular surface.
• Of prime importance appear to be the sex hormones but numerous other soluble factors
are also relevant
• ´Male´ sex hormones (androgens) and ´female´ sex hormones (estrogens and
progesterons) are actually present in both sexes - however in different proportions.

50. The endocrine system of hormones
• The sex hormones are in both male and female important for the growth
and differentiation of the organs in development
• The conjunctiva as well as the connected glands respond equally to the
hormones
• Much of the sex hormones are produced locally in the ocular tissues from
hormone precursors in the blood.

51. The endocrine system of hormones
• In adulthood, the function of the ocular surface tissues and particularly of
the glands seems to be more positively influenced by androgens in both
sexes
• This explains why females typically have a higher risk for Dry Eye Disease due
to the lower level of androgens
• changes of hormone levels in menopause can further disturb the
physiological function of the ocular surface.

52. Hormonal Regulation of Meibomian Glands
• blinking controls the release of meibomian gland fluid from the ducts of the
meibomian gland
• androgen sex steroids regulate meibomian gland lipid synthesis and
secretion
• these glands also contain enzymes that either convert testosterone and
dihydroepiandrosterone into the potent androgen, 5a‐dihydrotestosterone
or metabolize androgens into other androgenic forms

53. Neuronal Regulation of Meibomian Glands
• Another mechanism for the regulation of meibomian gland secretion
involves the nerves surrounding the acinar cells of the alveoli of the gland
• Neural control of the meibomian gland would be unique given that the other
sebaceous glands are not innervated
• Vasoactive intestinal peptide (VIP)‐containing nerves, probably
parasympathetic, are abundant and surround the acinar cells

54. Neuronal Regulation of Meibomian Glands
• Sympathetic and sensory nerves are also present, but are not as abundant as
parasympathetic nerves and are located mainly near blood vessels
• Neuropeptide Y (NPY)‐ containing nerves are also abundant with a similar
distribution as VIP
• Nerves could also regulate the release of lipids from the secretory granules
by stimulating fusion of the secretory granule and apical membranes.

55. Hormonal Regulation of Lacrimal Glands
• Hormones from the hypothalamic–pituitary–gonadal axis, such as α -
melanocyte stimulating hormone (α‐MSH), adrenocorticotropic hormone
(ACTH), prolactin, androgens, estrogens, and progestins have been shown to
exert a significant influence on the lacrimal gland
• Androgens are potent hormones that stimulate the secretion of SIgA and
cystatin‐related protein
• glucocorticoids, retinoic acid, insulin, and glucagon are also known to affect
various aspects of the lacrimal gland

56. Neuronal Regulation of Lacrimal Glands
• Parasympathetic, sympathetic, and sensory nerves innervate the lacrimal
gland
• Parasympathetic innervation provides the primary input
• Parasympathetic nerves are also located adjacent to duct cells and blood
vessels
• In the lacrimal gland, these nerves contain the neurotransmitters
acetylcholine, a muscarinic, cholinergic agonist, and VIP

57. Neuronal Regulation of Lacrimal Glands
• Neural reflexes are initiated by afferent sensory nerves in the cornea,
conjunctiva, and nasal mucosa responding to mechanical, thermal, or
chemical stimulation or by the optic nerve responding to light
• These activate the efferent parasympathetic and sympathetic nerves of the
lacrimal gland, which release their neurotransmitters
• The neurotransmitters interact with specific receptors on the basolateral
membranes of acinar and duct cells of the gland

58. lacrimal secretion has traditionally been divided into
Basal low-level secretion, Reflex secretion, Induced and Psychogenic tearing
BASAL SECRETION
• In the human eyes the cornea is continually kept moist & nourished by basal tears. They lubricate the
eye & help to keep it clear of dust
• Secreted by accessory lacrimal glands
• Previously, it was argued that the accessory glands provided basal tear secretion and the lacrimal gland
was responsible for reflex tearing. However, recent evidence suggests that all tearing may be reflex.
Secretion of Tears: Types

59. lacrimal secretion has traditionally been divided into
Basal low-level secretion, Reflex secretion, Induced and Psychogenic tearing
REFLEX SECRETION
• Results from irritation of the eye by foreign particles
• Can also occur with bright light & hot & peppery stimuli to the tongue & mouth
• These reflex tears attempt to wash out irritants that may have come into contact with the eye
• Secreted by main lacrimal gland Applied : If lacrimal gland malfunctions or is damaged in surgery or
other failure of lacrimal function occur, it is not a serious matter, for the accessory glands are enough
for general secretion
Secretion of Tears: Types

60. lacrimal secretion has traditionally been divided into
Basal low-level secretion, Reflex secretion, Induced and Psychogenic tearing
REFLEX SECRETION
• Results from irritation of the eye by foreign particles
• Can also occur with bright light & hot & peppery stimuli to the tongue & mouth
• These reflex tears attempt to wash out irritants that may have come into contact with the eye
• Secreted by main lacrimal gland Applied : If lacrimal gland malfunctions or is damaged in surgery or
other failure of lacrimal function occur, it is not a serious matter, for the accessory glands are enough
for general secretion
Secretion of Tears: Types

61. lacrimal secretion has traditionally been divided into
Basal low-level secretion, Reflex secretion, Induced and Psychogenic tearing
Induced tearing
• which often develops as an allergically or chemically mediated response to local irritants or by direct
nonsynaptic parasympathomimetic action of some drugs on the cAMP-dependent signal transduction
pathways in the secretory cells of the lacrimal glands
Secretion of Tears: Types

62. lacrimal secretion has traditionally been divided into
Basal low-level secretion, Reflex secretion, Induced and Psychogenic tearing
Psychogenic tearing
• tears of emotion, which are unique to humans
• Young infants cry without shedding tears during the first days of life, and infants born prematurely
may not shed tears for weeks
• This delayed capacity for psychogenic weeping suggests that the connections within the CNS that
indirectly innervate the lacrimal system are not fully developed in most newborns
Secretion of Tears: Types

63. Stability, Drying and Rupture of Tear Film
• The tears can function properly only if the tear film covers the entire preocular surface
and is re-established quickly and completely after a blink
• In the normal human eye, the precorneal tear film has a short-lived stability
• When blinking is prevented, after a brief time interval of 15-40 seconds, the tear film
ruptures and dry spots appear on various parts of cornea
• The drying of the corneal surface cannot be a result of evaporation of water alone,
because at least ten minutes would be required to eliminate the whole tear film by
drying only according to evaporation rates observed in vivo with the oily layer in place
• It is interesting to note that among the lower animals, the tear film can remain complete
for as long as 600 seconds between blinks

64. Mechanism of tear film break up
Holly (1973) has described a mechanism of tear film rupture. The steps involved in the break
up of tear film as per Holly's (also known as Holly and Lamp's mechanisms) are as follows:
• First of all the tear film thins uniformly by evaporation
• When the tear film is thinned out to some critical thickness, a significant number of lipid
molecules begin to be attracted by the mucin layer and migrate down to this layer
• This migration process is enhanced, if there is any spontaneous local thinning
• When the mucin layer on the epithelium is sufficiently contaminated by lipid migrating
down from the top surface of the tear film, the mucin becomes hydrophobic and the tear
film ruptures

65. Mechanismoftearfilmbreakup

66. Mechanism of tear film break up
• The blinking can supposedly repair the rupture by removing the lipid contaminant from
the mucin layer and restoring a thick aqueous layer
• Thus dry spot formation is essentially localised non-wetting, and not localised drying
caused by discontinuities in the superficial lipid layer
• As regards the location of these dry spots it has been noticed that these occur twice more
in temporal quadrant as compared to nasal one
• The suggested reason for these differences is that nasal areas are more protected against
air currents and have comparatively higher temperature.

67. Clinical disorders
Keratoconjunctivitis Sicca (Dry Eye)
• The broadest definition of dry eye is an insufficiency, qualitative or quantitative, of precorneal tear fluid
resulting in nonwetting and instability of the tear film
• It is an age related aqueous deficiency syndrome that is more common in women than in men
• Unstable tear film is considered the underlying cause of all dry eye syndromes.
• Tear fluids from KCS patients have greatly reduced levels of the three major lacrimal gland proteins: tear-
specific prealbumin, lysozyme, and lactoferrin
• However, sufferers can experience watering of the eyes, which is in fact a response to irritation caused by
the original tear film deficiency
• Lack of Meibomian gland secretion can mean the tears are not enveloped in a hydrophobic film coat,
leading to tears spilling onto the face.

68. "Crocodile tears syndrome“ - Bogorad's syndrome
• an uncommon consequence of nerve regeneration subsequent to Bell's palsy or other damage to the facial
nerve in which efferent fibers from the superior salivary nucleus become improperly connected to nerve
axons projecting to the lacrimal glands
• causing one to shed tears (lacrimate) during salivation while smelling foods or eating
• It is presumed that one would also salivate while crying due to the inverse improper connection of the
lacrimal nucleus to the salivary glands, but this would be less noticeable
Clinical disorders

69. Mucin Deficiency Diseases
• Patients show no quantitative or qualitative differences in any of the four high-molecular-weight
glycoprotein subunits found in mucin from normal individuals
• The classical example of a mucin deficiency caused by degeneration or loss of goblet cells is
hypovitaminosis A
• Vitamin A is necessary for the maturation of goblet cells; it also plays an essential role in the biosynthesis
of cell surface glycoconjugates
• Nonwetting of the ocular surface, one of the earliest signs of vitamin A deficiency, is generally attributed
to the loss of mucous glycoproteins
Clinical disorders

70. Blepharitis
• Functional abnormalities in the meibomian glands are believed to play a major role in the pathogenesis of
blepharitis.
• The normal outflow of lipid secretion is obstructed, and the retained lipids exacerbate the inflammation,
which may ultimately lead to necrosis of the gland
• It is also possible that modifications in the lipid composition lead to increased viscosity of the fluid, which
could impede its secretion from the gland.
• The formation of lipid-laden nodules or lipogranulomas (chalazion) throughout the eyelid is characteristic
of most if not all types of blepharitis
Clinical disorders

71. Tear film Components: summary
Tear Layer Origin Components Physiological functions
Lipid layer Meibomian gland
Accessory lacrimal gland
Wax, Cholesterol, Fatty acid ester Lubrication, prevention of
evaporation,
stabilization
Aqueous layer Lacrimal gland
Accessory lacrimal gland
Water
Electrolyte: Na+, K+, Cl-, HCO3-, Mg2+
Proteins: albumin, lysozyme, lactoferrin,
transferrin, ceruloplasmin, immunoglobulins (Ig
A, G, E, M) Cytokines,
Growth factors: EGF, TGF, VEGF
Others: Glucose Vitamins
Lubrication, antimicrobial,
bacteriostasis, oxygen supply,
nutritional supply,
mechanical clearance,
regulation of cellular functions
Mucous layer Conjunctival goblet cells,
conjunctival epithelial cells,
corneal epithelial cells
Sulfomucin, sialomucin complexes (SMC),
MUC1, MUC4, MUC5AC
Lowered surface tension,
Stabiliztion of aqueous layer

72. Lysozyme
• 20-40% of tear protein
• 1-2ug/ul
• Antimicrobial
• breaks the bond between sugars
• bonds that make up the backbone of the
peptidoglycan chains in bacteria
• Degrades cell wall
• Bacteria succumbs to osmotic gradient
Tear film summary
Phospholipase A2
• Powerful enzyme
• Breaks down phosphatidyl glycerol which is
main lipid components of the inner
bacterial membrane

73. Lactoferrin & transferrin
• iron binding proteins
• Sequesters essential iron from microbes
replication
Tear film summary
IgA
• Major antibody present in Seromucous
secretions
• e.g. saliva, tears where is in form of a
dimer called secretory IgA
• half-life: 6 days
Lipocalin or tear specific prealbumin
• AKA tear-specific prealbumin
• Binds lipids to help stabilize the tear film
• Sequesters harmful lipid philic molecules to
prevent epithelial interaction