Precorneal Tear Film Part 1 - Basic Science of the Tear Film Answers

what are the fxns of the precorneal tear film

1. provide a smooth refractive surface on the cornea

2. allow diffusion of oxygen and other nutrients

3. flush material form the surface of the eye

4. maintain health of cornea and conj ep

5. lubrication of lids and globe

6. medium for antimicrobial agents

describe the updated 2 phase model of the tear film

new tear model has a surface lipid layer and mucoaqueous layer

describe the sources of the lipid layer of the tear film

1. meibomian glands and glands of zeis

describe the phases of the lipid layer of the tear film

outer non polar lipids - prevents evaporation and barrier to pathogen

inner polar lipid - acts as a surfactant to facilitate interaction w mucoaqueous layer - helps mucoaqueous layer spread over cornea

functions of the lipid layer of the tear film

1. reduce evaporation (main fxn)

2. lubrication

3. barrier to pathogens

4. increase spread ablity of tear film by lowering surface tension of tears

characteristics of the tear film

1. secretion of meibomian gland

   1. melting range

      1. allows for good viscosity of meibomian oil and spread ability

   2. secretion is a continuous process over 24 hours

   3. evidence of neural, hormonal, and vascular influences

   4. increase in production w age and androgen production

   5. decrease in production w DED and menopause

describe the sources of the aqueous component of the Mucoaqueous layer

main lacrimal gland and accessory lacrimal glands

list the 4 main components of the mucoaqueous layer

1. 98 % H2O

2. tear film solutes

   1. glucose

   2. vit A

   3. vit C

   4. AA

   5. lactate

3. aqueous electrolytes

   1. Na

   2. Cl

   3. K

   4. HCO3-

4. aqueous proteins

how does the cornea respond to oxygen supply in the tear film w the eyes open vs the eyes closed

1. eyes open

   1. tear film has high oxygen

2. eye closed

   1. tear film has low oxygen

list the aq solutes of the mucoaqueous layer and their fxns

1. glucose - low levels to prevent bacterial growth, cornea gets most of its glucose from ant chamber

2. vit A - need goblet cells and epithelial maintenance

3. vit C (ascorbate) - important antioxidant in tears

4. lactate - byproduct of metabolism

list the major aq electrolytes of the mucoaq layer and their fxns. Describe any clinical significance of abnormalities in electrolyte levels

1. HCO3 - buffers tears - regulates tear pH

2. NaCl and KCl or K, Na, Cl - found in higher levels as a part of active secretion

   1. these regulate osmotic flow of fluids between corneal ep cells and tear film

   2. imp to have normal tear film electrolyte balance to prevent corneal edema

   3. clinical pearl - treat corneal edema w hypertonic saline to dehydrate cornea

   4. clinical application:

      1. chronic hypertonic tears

         1. damages the ocular surface - triggers inflammation and dry eye

3. others

   1. Fe2+

   2. Cu

   3. Mg

   4. Ca

      1. all are enzyme cofactors for controlling membrane permeability

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: lipocalin

1. important for tear film stability

2. binds to meibomian lipids

3. prevents infections by inhibiting siderophores (transport iron across cell mems)

4. increases viscosity of tear film

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: sIgA

1. prevents adhesion and colonization of bacteria

2. prevents attachment of viruses

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: IgG

1. low levels

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: lysozyme

degrades cell wall of GM + bacteria

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: lactoferrin and transferrin

1. binds iron - prevents bacteria growth

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: IgE

allergic reactions

describe the significance and fxn of all major aq proteins especially as it relates to the prevention of eye infection - these proteins include: phosolipase A2

degrades phospholipids

- antibacterial vs GM + bacteria

describe the cytokines and growth factors involved in maintain ocular surface and controlling wound healing

they regulate epithelial proliferation, mobility, and differentiation

fxn of MMP9 in corneal wound healing and how is it associated w dry eye disease

1. MMP9 breaks down collagen, ECM, and BM proteins and therefore is involved in the breaking down and remodeling following a corneal wound

2. the levels of MMP9 are elevated in dry eye disease in pts that have corneal damage

3. MMP9 levels are measured clinically in DED and elevated levels often represent a more severe form of DED

fxns of mucins in the mucoaqueous layer

1. fills in irregularities of corneal surface

2. mixes w the aqueous to create a hydrated gel like state

3. reduces the surface tension of the aq layer for spread ability of tear film

4. removes contaminants, debris and cells from the tear film

   1. are rolled into threads to be drained via the nasolacrimal system

discuss the types, sources, and functinos of secretory mucins found in the mucoaq layer of the tear film

1. gel forming mucins

   1. large mucins from goblet cells of conjunctiva

   2. scavengers of tears

   3. remove foreign materials

   4. make tear film more hydrophillic

   5. hydrate cornea

2. soluble mucins

   1. lacrimal gland and stratified squamous cells of conj

   2. make tear film more hydrophillic

   3. hydrate cornea

discuss the source and fxn of membrane anchored mucin in the muco aq layer

1. secreted by corneal ep cells and conj ep cells

2. attach to glycocalyx

3. fxn:

4. adhere tear film to corneal surface

5. protect and hydrate corneal ep

describe the list of ocular defense mechs that prevent eye infections

1. rapid reflex blinking

2. flushing effect of tears

3. water soluble components of tears

4. lysozyme - GM + degrades cell wall

5. tear lipocalin - sequestering microbial siderophores - reduces iron

6. lactoferrin - binds iron

7. phopsholipase A2 - degrades phospholipids - GM -

8. SIgA - antiseptic paint

9. IgG - promotes phagocytosis

10. gel forming mucins - entraps material in threads

11. ep of cornea is a physical barrier

describe the physio chemical properties of tears including: water levels

98%

describe the physio chemical properties of tears including: thickness

3.4 microns

describe the physio chemical properties of tears including: volume

7.4 microliters

describe the physio chemical properties of tears including: pH

6.5 - 7.6

describe the physio chemical properties of tears including: osmolarity

302 mOsmol/L

range 296 - 308

describe the physio chemical properties of tears including: temperature

35 centigrade - at central cornea

describe the physio chemical properties of tears including: viscosity

low viscosity to avoid ep damage from shearing forces

basal tears

open eye tears

constitutively or continuously produced and continuously coat the ocular surface

reflex tears

produced in resposne to stimulus of V1 mostly (sometimes V2 or V3)

environmental stimulus like pain, heat, pressure

closed eye tears

produced continuously when you are asleep or when your eyes are closed

like basal tears but a bit different bc proteins enter from conjunctibal blood vessels

what are the 4 broad types of tears based on production

1. basal

2. reflex

3. emotional

4. closed eye

what is the normal rate of tear production

1.2 microliters per minute

reflex arc for tear secretion

1. afferent stimuli mostly from V1 (can be from other branches of V)

   1. gives feedback from the environment

   2. mechanical, chemical, or thermal stimuli to brain stem to facial nerve

2. efferent - mostly parasympathetic (some sympathetic)

   1. stimulates tear secretion by lacrimal

   2. new research shows some innervation to meibomian glands and goblet cells

      1. activates mucous and lipid secretion

describe how the neural regulation of tear production maintains normal homeostasis of the tear film for basal tears

1. afferent —> low level of sensory info from corneal and conj trigeminal nerves is conducted to brain stem lacrimal nucleus

2. the efferent pathway is via the parasympathetic fibers of the facial nerve and some sympathetic fibers that signal the lacrimal gland secretion

   1. there are some efferent fibers that stimulate the goblet cells and meibomian glands for mucin and meibum secretion (theory)

   2. this occurs all of the time as a form of surveillance of the env to make sure the ocular surface always has the appropriate volumes of tears

describe how neural regulation controls tear production during reflex tearing?

same process as basal tearing except the afferent stimulus - it is a stronger environmental stimulus

• considered a noxious stimulus

• mechanical, chemical, or thermal

• mostly V1 can be V2 or V3

the stimulus goes to the brainstem to the lacrimal nucleus

efferent

via the parasympathetic fibers of the facial nerve and some sympathetic fibers that signal the lacrimal gland secretion

you will find there is usually a significant increase in the volume of tears due tot he increased output by the main lacrimal gland

this is an excellent protective mech

there are some efferent fiberst hat stimulate the goblet cells and meibomian glands for mucin and meibum secretion (theory)

how is neural control of tear film disrupted in dry eye disease

1. pt w an abnormal tear film in dry eye disease can have ep damage

2. this can cause the release of cytokines

3. the cytokines block the release of NT from the trigeminal nerve

4. this disrupts the normal reflex arcfor basal and reflex tearing

5. this can lead to a dec in tear production in a pt that needs additional tears (dry eye pt)

6. as more cytokines are relased the dry eye worsens and this is an unfortunate cycle for the pt and needs to be addressed in the management

describe factors necessary for proper wetting of the cornea

1. intact corneal ep cells w glycocalyx

2. good lid globe congruity

3. adequate tear production

4. periodic resurfacing - normal blink rate

5. surface tension of the tear film needs ot be lower than the cornea

how do the interactions of the tear film components change the surface tensions to allow for wetting of the cornea

1. surface tension of the aq component of the tear film is reduced by the lipid layer and mucins and proteins from mucoaq layer to lower the surface tension of the water in the aq layer

2. the water will not want to bind to itself but with the other components of the tear film —> will want to spread over the corneal surface

describe tear film formation or how a fresh tear film is produced during lid closure

1. 1. as the eyelids close there is resurfacing of the tears

   2. mucin is rolled into threads

   3. goblet cells produce more mucin

   4. as upper lid meet lower lid lipid is released from Meibomian glands

describe tear film formation or how a fresh tear film is produced during lid opening

1. the lipid layer is spread ober the muco aq layer adn the mucin layer resurfaces over corneal surface

2. the muco aq layer is pulled form the tear meniscus

describe how the tear film is ruptured and how this relates to the clinical test: TBUT

1. as the eyes are held open the tears evaporate and there is thinning of the tears

2. the tear film retracts from the corneal surface

3. a dry spot forms

4. CN V is stimulated and a reflex blink occurs to resurface the tear film

5. break up time is the # of sec it takes a dry spot to occur inthe tear film as noted by the absence of fluorescein dye on the corneal surface

6. less than 10 sec is clinically significant

discuss evaporation of the tear film and what causes increased evaporation

1. a normal lipid layer is most important to prevent evaporation

2. abnormal mucin can also increase evaporation rate

3. increased evaporation occurs in low humidity, wind, air conditioning, use of eye drops, and contact lens wear

how much of tears are absorbed and where are they absorbed

1. absorption rates up to 2 microliters/ min have been recorded

2. tears are absorbed thru mucosal surfaces like the conj and nasolacrimal duct

discus the effects of contact lenses on tears

1. interfere w the tear film and cause the tears to have a layer btw the lens and cornea and a layer in front of the lens

2. this interferes w the physiology of the tears

3. this increases evaporation of the tears, degrades the mucin of hte tear film, impairs the lipid layer, and causes stagnation of tears beneath the contact lens

discuss the physiologic variation of the difference of the open eye versus the closed eye

1. when the eyes are open the tear film has

   1. more oxygen

   2. more normal pH

   3. normal blinking

2. when the eyes are closed (sleep)

   1. less oxygen

   2. more acidic tears

   3. more proteins from conjunctival blood vessels

discuss the physiological variation of the aging changes in tear film

1. w the aging process there is a dec in tear volume and tear flow due to a decrease in output of the lacrimal gland

   1. the tears become more hypertonic

   2. have less tear proteins like lysozyme and lactoferrin and are less able to fight ocular infections

   3. meibomian gland secretions decrease so the lipid layer is less stable —> the tear film evaporation increases

tear drainage system

1. lacrimal lake

2. lacrimal puncta

3. canaliculi

4. lacrimal sac

5. lacrimal duct

6. inferior meatus of the nose