Physiology of Cornea and Tear Film Flashcards
What are the layers of the cornea starting most anterior?
Epithelium (55um), Bowmans layer (5um), Stroma (485um), Descemets membrane (10um), Endothelium (5um)
Focusing system of eye?
cornea, aqueous, iris, crystalline lens, vitreous
Imaging system of eye
retina, optic nerve/tract, visual cortex
How does cornea anatomically stay transparent
avascular, non pigmented cells, un-myelinated nerves, optical surface (tear film)
*collagen fibril orientation: equal diameter and separation. Specific arrangement generating constructive interface
Epithelium for transparency
semi permeable membrane
tears/epithelium:
- Na+ movement by passive diffusion
- Cl- actively pumped to tears, creates water gradient towards tears
epithelium/stroma:
- Requires energy Na+K+ATPase transporter
Endothelium for transparency
permeable membrane
aqueous humour to stroma:
transports glucose, amino acids and nutrients driven by IOP and stroma pressure
Stroma to Aqueous Humour:
- pumps fluid into aqueous humour
- Bicarbonate pump
- Carbonic anhydrase within cell
- Na+K+ATPase pump
- lateral cell walla
Corneal Function - Metabolism
energy needed to maintain corneal hydration
epithelium –> tears passive (osmosis)
Stroma –> epithelium active
what is glucose stored as?
glycogen in epithelial cells
what is glycolysis?
enzymatic breakdown of glucose to pyruvate and energy
oxygen needed for aerobic metabolism
Epithelial function - nutrient source
nutrient supply via tear film + aqueous
glucose –> epithelial glucose from AqHumour (diffusion through stroma and endothelium)
Oxygen –> no blood vessels so mostly atmospheric diffusion from tears. When eyelids closed palpebral conjunctiva is source
Aerobic Epithelial Function
glycolysis via two mechanisms:
Krebs cycle –> conversion of pyruvate by mitochondria lead to generating ATP (energy)
Pentose phosphate pathway –> oxidises glucose to generate NADPH, fatty acid synthesis, glycolysis
Anaerobic epithelial function
glycolysis via two anaerobic mechanisms:
- pentose phosphate pathway. Oxidises glucose to generate NADPH, fatty acid synthesis and glycolysis
Anaerobic pathway produces pyruvate and lactate that breaks down CO2 and H20. Increased acidity, cellular damage, dysfunction
Endothelial function -metabolism
oxygen delivery via AqHumour. Independent of eyelid closure
Glucose vis AqHumour
Glycolysis and ATP generated mostly from Krebs cycle. High density of mitochondria
Uses alot of energy due to high metabolic demand for ion transport
Corneal function - Defence
epithelium major defence mechanism:
- absence of vascular system
- tight junctions and tear film
Epithelium turnover
rapid wound healing. 24-48 hours
epithelial cell migration, monolayer slides over wound within 5 hours
cell proliferation at the limbus to support migration
cell adhesion, rapid from plaque adhesion to hemidesmosomal complexes
keratocytes (fibroblats) dormant until compromise (injury, inflammation)
endothelial repair
Cell density: Birth 5000 (cells/mm2) Age 5 - 3500 Teenager - 3000 Adult - 2500
Coverage compensation:
Lost cells are replaced by expansion and thinning of neighbouring cells
Leads to variation in cell shapes (polymorphism) and sizes (polymegathism) with age
how do tears stick to corneal surface?
- corneal microvilli
- membrane spanning mucus
- secreted mucus
sticky surface with water soluble glue
Tear film - function
- maintains health of ocular surface; proteins, nutrients
- acts as a lubricant for lid and corneal interaction
- disposal system to wash debris away and dilute toxins
- optically smooth surface
Tear film - composition:
Three components:
- inner mucin layer
- aqueous phase (bulk)
- outer lipid layer (most anterior surface)
A mucin gradient exists between inner mucin layer and aqueous layer
What is mucin layer
product of corneal and conjunctival cells
sticks tear film down, anchors aqueous phase to corneal surface
lubricant
bounding of debris/ bacteria
what is aqueous layer
liquid layer
volume of tears from lacrimal gland
source of electrolytes, proteins, peptides and oxygen
removal of debris, bacteria
what is lipid layer
stops tearms from evaporating
acts as lubricant
produced by meibomium glands (eyelid margins)
source of tear film
mucin –> conjunctiva, squamous and goblet cells
aqueous –> lacrimal glands, acinus sacs
Lipids –>
Meibomium glands, acinus sacs
tear film mucins
Combination of secreted:
- Goblet cells (MUC5Ac)
- Lacrimal gland (MUC7)
- Mixes in aqueous phase
- Cleaning up debris
Membrane spanning:
- Epithelium, cornea, conjunctiva
- Forms glycocalyx (glue)
MUC1, MUC4 and MUC16
4 major proteins found in tear film aqueous
Lysozyme:
(2.07 mg/ml), a potent antibacterial enzyme, by hydrolysing the bonds in the outer wall of the bacteria (G+ve, streptococcus and staphylococcus)
Lipocalin:
(1.55mg/ml), plays a lipid binding role, maintains the surface tension of the tears. Binds with fatty acids which enhances function of Lysozyme
Lactoferrin:
(1.65mg/ml), antimicrobial (G+ve and G-ve Pseudomonas, Eschericha coli, Haemophillis influenza) binds to free iron preventing use by bacteria.
Part of innate defence mechanism
Secretory IgA:
(1.93mg/ml), part of the adaptive response system, adheres to bacteria thus a target for phagocytosis
Other –> (0.1mg/ml)
Aqueous largest component of tears. little glucose, also of K+ and Cl-
tear film lipid layer
Produced by meibomian glands:
- Modified sebaceous glands that secrete meibum
- Mixture of lipids and proteins
- Differs to seibum (more viscous)
- Very thin complex oily layer (15-160nm)
- Mixture of polar, non polar and neutral lipids, >236 lipids isolated
- Melting point 19.5-32.9 degrees - always fluid on ocular surface
Optical finishing touch Retard evaporation Evaporation - aqueous layers thin Surface destabilises Non-wetting patches appear Poor optical performance
Observation easier:
Instillation of water soluble dye
Sodium fluorescein
Clinically known as Tear Break Up time TBUT
Temperature gradient:
Ocular surface 37 degrees (body temp)
Air –> ambient 24 degrees
Tear film must evaporate. Limited by lipid layer
Tear film needs:
- Replacing
- Refreshing
Reforming
four phases of blink action
downstroke - upper lid to lower lid
turning point - lid stops before reversing motion
upstroke - upper lid moves away from lower lid
interblink - pause before downstroke
function of blink
downstroke –> regenerates aqueous phase, sweeps mucin wrapped debris nasally
turning point –> forms new lipid layer
upstroke –> spreads lipid layer over tear film
interblink –> pause before downstroke. Vision processing
types of tears
basal - mediated by Na+K+ATPase
reflex - parasympathetic control. sensory stimulation, retinal stimulation, pain, emotions
primarily through increased aqueous volume orbital/palpebral lobes of lacrimal glands
corneal dysfunciton
opacification:
corneal dystrophy, opacification due to infection, cornea filled with blood vessels, stroma increasing thickness odema (milky cornea), plaques
tear dysfunction:
Stability:
- Aqueous dysfunction
- Lipid dysfunction
- Mucin dysfunction
Ectropion
TBUT
Dry Eye
what is osmolarity
The concentration of an osmotic solution, measured in litres, the total number of particles dissolve in a solvent
For tears: - As aqueous reduces - Salt concentration increases - Osmolarity increases (hyperosmolarity) Symptoms of dry eye increase
