6720 - Tears and Lacrimation

function of tear film

maintain smooth optical surface, O2/nutrient supply for cornea, debris collection, pathogen defense, hydration, wound repair, lubrication

layers of tear film (most external to most internal)

lipid layer, aqueous layer, mucous layer, glycocalyx, ocular surface

central tear thickness

3 micrometers

meniscus tear thickness

270 micrometers

lipid layer thickness

50-100 nanometers

tear volume

6.5 microliters

production and drainage-evaporation rate

1.2 microliters per minute

basal tears

continuous basal rate of lacrimal secretion

what tears decrease with age?

basal secretion

reflexive tears

response to external stimuli, increases basal secretion

what tears are not found in infants?

reflexive tears

what external stimuli increase reflexive tears?

temperature, chemical irritation, pressure, nasal, photo-lacrimal

psycho-emotional tears

crying when sad, unique to humans

what are the four dominant solutes found in tears?

sodium, chlorine, potassium, bicarb

ion transportation in tears

transported across plasma membranes of lacrimal and ocular surface cells for the purpose of transporting water

what is the purpose of bicarb in tears?

buffers tear pH

what percentage do tear proteins/sugars make up in tears?

less than 1 percent

glucose concentration in tears

7.4 mg/dl

does tear concentration of glucose correlate with blood glucose?

yes

which tear layer is isotonic?

aqueous layer

what percentage of NaCl is found in the aqueous layer?

0.97%

what is the osmolality of the aqueous layer?

about 300 mOsm/kg

isotonic tears

tear production equals tear drainage and evaporation

hypertonic tears

there is more tear drainage and evaporation than there is tear production

hypotonic tears

there is more tear production than there is tear drainage and evaporation

osmometer

used to determine the severity of dry eye

what affects the osmolality/tonicity of tears?

environment (humidity, air movement, temp), sleep/time of day, contact lens, age, gender, race

what do contact lenses do to the tear film?

decrease in lipid layer, decrease in mucin proteins, separation of aqueous into pre/post tear film

what is the average pH of our tears?

~7.5

when do our tears have lower pH?

after sleep, during contact lens wear, in newborns

what is the result of having more acidic tears?

reduced oxygen, more anaerobic metabolism, more lactate ion production

what is the range that our tears are able to maintain pH?

3.5 to 8

temperature of tears

35-36 degrees celsius (95-96 degrees F)

what causes our tears to increase in temperature?

palpebral closure

what causes our tear to decrease in temperature?

dry eye

what is more viscous, tears or water?

tears

what creates the viscosity of the tear film?

lipid layer

shear-thinning property

more shear force (during blinks), less viscosity

less shear force (interblink), more viscosity

refractive index and tears

linear relationship between refractive index and osmolality of tears

approximate RI of tears

1.33

tears and optical quality

optical quality improves after blink and then slowly gets worse over time

what causes poor optical quality?

non-uniform tear distribution, non-uniform tear break up

non-uniform tear distribution causes

position of meibomian glands, incomplete blinks, irregular surface features

TBUT

tear film break up time, measures how long it takes for your tear film to break up

keratoconjunctivitis sicca epidemiology

women (post-menopausal), older>younger, diabetes

lacrimal functional unit

lacrimal glands, ocular surface (cornea & conj), meibomian glands, palpebrae, sensory and motor nerves

what causes hyperosmolarity (hypertonic) tears?

decreased tear quality (more evaporative), decreased tear production (aqueous-deficient)

what causes dry eye?

hypertonic tears

what can chronic hypertonic tears lead to?

damaged ocular surface cells which leads to inflammation and decreased cornea sensitivity

how does decreased corneal sensitivity affect tear production?

decreases tear production

what are the 3 main cell types found in the lacrimal gland?

ductal cells, acinar cell, myoepithelial cells

which cells are the main contributors to aqueous production in the lacrimal gland?

acrinar cells

which cells are interdigitated by autonomic nerves?

acinar and myoepithelial cells

what do myoepithelial cells contain?

alpha-smooth muscle actin

where do you find epithelial tissue?

exterior surfaces, lining internal cavities, forms glandular tissues

true or false: Tight junctions define the apical and basolateral membranes of an epithelial cell

true

true or false: Increased tear evaporation would be expected to cause the tear film to become hypotonic

false

what is the apical most junction type?

tight junctions

what are tight junctions important for?

restricting paracellular water movement

what is the defining feature of tight junctions?

separating plasma membrane regions

adherens junctions function

adheres plasma membranes of adjacent cells

what are adherens junctions made of?

cadherin and catenin proteins

what do adherens junctions associate with?

cytoskeleton (mostly actin)

desmosomes function

adheres plasma membranes of adjacent cells

what do desmosomes associate with?

cytoskeleton (mostly intermediate filament)

what are gap junctions made of?

connexon proteins

gap junctions function

form ion channels allowing ions to pass across the plasma membrane

paracellular pathway

transport of substances through the intercellular space between the cellswh

what allows small molecules to pass through paracellularly?

extracellular domains of tight junction proteins (claudins)

transcellular pathway

moving through the cell

passive diffusion

cell membranes are hydrophobic and form a barrier to charged molecules

what types of molecules are allowed through with passive diffusion?

small gases, hydrophobic, polar, and uncharged molecules may pass across membrane

what cannot pass through via passive diffusion?

large polar molecules (glucose), any charged molecule

what are electrochemical gradients a combination of?

electrochemical potential and concentration gradient ; charges and concentration of solutes on either side of the membrane

electrochemical potential

the difference of the combined charges of the ionic environment on either side of the plasma membrane

concentration gradient

the difference of the solute concentration on either side of the plasma membrane

uniporter

moves one type of ion

symporter

simultaneously moves multiple ions in same direction

antiporter

simultaneously moves multiple ions in opposite directions

what does channel mediated transport move?

small ions

what does carrier mediated transport move?

small molecules

active transport

moving a molecule against its concentration gradient; uses energy

how does water move paracellular?

driven by osmolality/tonicity differences; created by transport proteins

NKA

Na+-K+-ATPase

NHE

Na+/H+

AE

Cl-/HCO3- (antiporters)

NKCC

Na+, K+, 2Cl- co-transporter

uniporter in lacrimal gland

calcium sensitive Cl- and K+ channels

mutation in claudin 10b gene

causes alacrima, mutation causes disrupted formation of aqueous pores in claudin protein, water and sodium can't get through

alacrima

lack of aqueous

CFTR mutation

major gene disrupted in cystic fibrosis

what ocular symptoms do CF patients have and why?

CFTR mutation causes apical chloride channels to be misshapen which prevents chloride ions from moving into the lumen, this decreases aqueous content of tears leading to dry eye symptoms

what is the lacrimal gland innervated by?

autonomic and sensory nerves - parasympathetic nerves predominate

what is the primary inducer of aqueous secretion?

parasympathetic stimulation

gap junctions

allow small molecules to pass between cells, stimulus in neighboring cells can trigger secretion

what receptors do parasympathetic target organs have?

muscarinic receptors

what receptors do sympathetic target organs have?

adrenergic receptors

what specific NT/receptor pair is found with lacrimal sympathetic nerves?

norepinephrine/alpha 1D receptor

what effects do antimuscarinic drugs have on lacrimal secretion?

decreased lacrimal secretion due to inhibition of M3 receptors

what specific NT/receptor combos are found in with lacrimal parasympathetic nerves?

1. acetylcholine/M3 receptor

2. VIP/VIP receptor