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Flashcards in CorneaSclera2 Deck (76):
1

What type of junctions are in the endothelium? What is the function of the tight junctions?

tight junctions; macula occludens
Function: barrier but not as good as epithelium
Do NOT encircle the whole cell
leaky barrier between stroma and aqueous

2

What is the function of gap junctions in the endothelium? Where are they mostly located?

Intercelluar communication; do not form barrier

mainly located in the lateral membranes ; , although some are also present at the junctions of the apicolateral membranes

3

What are two factors that contribute to prevention of corneal swelling? What percentage is water maintained at?

1. pumping function of endothelial
2. barrier function of endothelial

The barrier is incomplete compared with the epithelial barrier.

78%

4

When the endothelium is disrupted, cornea swelling is at what amount?

127 µm/hr

5

When the pump is disrupted cornea swelling is at what rate?

33 µm/hr

Represents movement of fluid and solutes from the aqueous humor into the stroma

6

Why is the normal leakage of fluid to the cornea vital ?

This is how cornea gets nutrients (glucose and amino acids) for the cornea
(since cornea is avascular)

7

Temperature Reversal of cornea and how it relates to swelling

Temperature has an effect on the corneal swelling; cooler temperature causes cornea to swell; normal temperature= normal corneal thickness


Early studies showed that maintenance of corneal thickness/water content is temperature dependent (a metabolic energy-dependent process)


Temperature reversal is clearly demonstrated by eye bank corneas, which swell during refrigeration and return to normal thickness and transparency after grafting.

8

How much water is moved by endothelium from stroma to aqueous humor?

6 to 8 ml/hr of water is moved by the endothelium from stroma to aqueous humor.

9

Endothelial Ion Transport

Driven by Na/K ATPase Pump located in basolateral membrane

present in normal humans at approximately1.5 x 106 pump sites per cell. The activity of Na+K+ATPase is vital to the maintenance of normal corneal hydration.

10

What inhibits the pump in the endothelium?

Ouabain: inhibits the pump
stops sodium transport, causes corneal swelling, prevents temperature reversal, and eliminates the transendothelial potential difference

11

Another reason pump responds?

responds to increases to endothelial permeability

human corneas with guttata have pump site densities of 6 x 106 sites per cell, which suggests a greater capacity for the endothelial pump to counteract the leak across the barrier.

12

What is gutatta?

droplet-like accumulations of non-banded collagen on the posterior surface of Descemet's membrane.

13

Inflamed Edematous cornea

has decreased endothelial pump sites despite increased permeability.

14

What is the sodium potassium ATPase and functions?

enzyme located in plasma membrane of cells

Functions:
1. Control of Hydration of cornea
2. Production of aqueous humor

15

Na, K-ATPase and corneal hydration

Corneal stroma readily takes up water.
Excess water needs to be pumped out to maintain corneal deturgescence
Sodium ions is transported by Sodium Pottassium ATPase is pumped into channels between endothelial cells


Na ions being pushed generates osmotic pressure
To which water follows
The directionality is helped by density of sodium ions in Descemets membrane

16

Endothelial wound healing

endothelial cells do not regenerate


Defects are covered by the spreading of cells from adjacent areas

When a large defect occurs, as a result of a keratoconus problem, more extensive cell migration occurs

17

Ideal irrigating solution should contain?

buffer- bicarbonate
energy source- glucose
substrate- calcium, glutathione etc.

18

T/F LASIK had an effect on endothelial cell density or percent of hexagonal cells

False, there was no significant change

19

How many microns are needed for cornea to continue normalcy? adequately maintain and protect the corneal endothelial structure and barrier function.

200 microns

20

Na ions in the pump and directionality of them

Na ions being pushed out generates osmotic pressure
Water follows the Na
Directionality is helped by density of sodium ions in Descemet's membrane

21

Irrigating system soultions
What do poorly buffered solutions expose?
Best soultion?,

they expose cornea to pH extremes and may cause edema

GBR

22

Why is saline not a good buffer?

It lacks components of aqueous humor

23

How do endothelial cells react to trauma? Large defects?

1. They don't regenerate
2. cells spread out to cover wounded area
3. when larger defects, more migration of cells occurs

24

Where do cells move after migration? What do they form?

move peripherally; form tight junctions to form endothelium barrier

25

For proper corneal function there must be?

1. adequate endothelial cell density
2. uniform size and shape of cells

26

what is polymegathism and pleomorphism? How does age relate?

Polymegathism
A change in cell size
Pleomorphism
A change in cell shape
Both polymegathism and pleomorphism increase significantly with age

27

What is CV and what is the normal CV?

Coefficient of Variation (CV):
Standard deviation of mean cell area
Mean cell area
Normal endothelium CV ≈ 0.25

28

how much does the cornea have hexagonal cells?

Healthy cornea has 70-80% hexagonal cells
A ⇩in hexagons with an ⇧in cells with < 6 sides shows endothelial stress = pleomorphism

29

CV and LASIK

CV improves 3 years after LASIK but this is secondary to the patients that wear contacts

30

What is cell count loss in those whove had PK

7.8% cell loss each year after 3-5 years of surgery. 13X higher than those with normal cornea

31

Amount of endothelial cell loss after cataract sugery?

8.5% after 12 months ; lens adds 20 D

32

How does cornea change in patients with KCN and Diabetes 2

morphology changes
cell density does NOT change
CV increases
Hexagonal cells drop to 50%

expect high astig or high myopia

33

Cell density in Glaucoma Pts

cell density decreases
IOP increases
special care to these pts so that surgical stress to endothelial doesnt occur

34

How does Polymegathism reported with long-term use of rigid polymethylmethacrylate lenses as well as with daily and extended-wear contact lenses change cornea?

morphologic abnormalities

contact lens-induced hypoxia is responsible for the observed effects on the endothium

CLUE syndrome, or contact lens-use endotheliopathy syndrome, to describe these effects.

35

Nerves of cornea?

sensory nerves from trigeminal nerve


But the Descemet’s membrane and the endothelium are NOT innervated in humans

36

What are nociceptors?

corneal receptors

stimulation results in perception of pain

The receptors usually have the lowest threshold for mechanical stimulation
This is why corneal abrasions, ulcers, and bullous keratopathy are all extremely painful conditions

37

What leads to corneal denervation? and what does this cause?

Herpes simplex, stroke, diabetic neuropathy

Sensory denervation causes epithelial erosions and neurotrophic ulcers


The loss in foreign body sensations cause mechanical cornea damage

38

What causes a decrease in cornea and conjunctival sensitivity?

LASIK up to 16 months
CL wearers

39

Corneal metabolism depends on oxygen from

atmosphere (mostly)
limbal vasculature
aqueous humor

40

O2 in aqueous humor vs tear film

stroma vs epithelial

Amount of O2 present in the aqueous humor is low compared to the tears
Epithelium consumes 10x more O2 compared to the stroma

41

How is oxygen delivered to cornea while sleep?

through vascularized superior palpebral conjunctiva

21% eyes open
8% eyes closed
even less if sleeping in CLs

42

Oxygen after cataract surgery

After cataract removal (ie aphakia), oxygen tension may increase in the aqueous humor as a result of decreased oxygen metabolism by the crystalline lens.

Thus,in the aphakic eye, oxygen in the aqueous humor may supplement oxygen dissolved in the tears, better meeting the corneal oxygen demands and allowing greater tolerance to hypoxic stress such as contact lens use.

43

Metabolic requirements for cornea

supplied by aqueous humor via ciliary body
epithelial has glucose from glycogen stored

44

Oxygen with CL wearers

contact lens wear causes a decrease in available oxygen to corneal epithelium
Hard contact lens nearly 80% of reserve used up in 8 hours of wear
Resulting in corneal edema (20% increase in corneal thickness)

45

Embden-Meyerhof pathway

Glucose derived from the aqueous humor or from epithelial glycogen stores is converted to pyruvate by the anaerobic Embden-Meyerhof pathway (ie glycolysis), yielding two molecules of adenosine triphosphate (ATP) per glucose molecule.

46

Under hypoxic conditions what causes corneal edema?

What are symptoms of epithelial edema, stroma edema?

increase in lactate production

Symptoms of epithelial edema:
Halo and rainbow formation
Increased glare sensitivity
Decreased contrast sensitivity

Stromal edema manifests in the posterior direction
Buckling of the stroma and Descemet’s membrane cause vertical striae

47

CL wearers and metabolism

Deturgescent cornea can be maintained with a sustained oxygen level as low as 25 mm Hg
Small-diameter hard lenses- PMMA
Impermeable to oxygen
Good movement needed for tear exchange
Large-diameter soft lenses
Oxygen permeability needed for diffusion through the lens itself
Tear pump exchange also helps to a lesser extent

48

Underlying mechanism for polymegathism?

Underlying mechanism: Certain byproducts of long term hypoxia and stress that is12HETE (12-Hydroxyeicosatetraenoic acid)
has the ability to inhibit the Na+K+ATPase of the endothelial metabolic pump

Only occurs after long-term, volume-regulation stress (example CL wear) and in the corneas of diabetic patients

49

How is metabolism altered in Extended Wearer CL

EW lenses alter metabolism and have been associated with:
Decreased rate of mitosis
Reduced oxygen uptake and glucose utilization
Smaller numbers of intercellular desmosomes
Because of these and reduced metabolic activity- the epithelial barrier function is compromised
Increased likelihood of ulcerative microbial keratitis

50

Lack of vitamin A causes what? and what is vitamin A required for?

Xerophthalmia
Keratinization of the epithelium;with the corneal epithelium expressing keratins normally found in skin by terminally differentiated superficial epithelial cells.

Primarily found in children of developing countries

Required for mucin production

51

Drug Penetration

The volume of the normal adult tear film is 7 to 9 µL, and the maximum amount of fluid that the cul-de-sac can maintain is 20-30 µL. This much of the 50 µL in the average drop of topical medication runs out of the eye immediately after instillation and the remainder is diluted in the preexisting tear film.

Reflex tearing caused by irritating or hypertonic solutions results in more rapid tear dilution.

Increased protein concentration in tears bathing inflamed or infected eyes may also decrease the bioavailability of drugs that bind to the protein.

52

How does corneal epithelium affect drug penetration?

Initial barrier: Epithelium (tight juctions)
Limit adsorption of hydrophilic, ionized substances
Favoring penetration of lipid-soluble hydrophobic compounds

Loss of corneal epithelium greatly enhances penetration of hydrophilic water-soluble pharmacologic agents

53

Stroma and drug penetration

The hydrophilic nature of the stroma results in a barrier to lipid-based drugs.

54

Drug penetration through endothelium

Drug penetration through the corneal endothelium is determined mostly be molecular size.

55

How do you increase drug penetration?

by increasing duration of the contact of the drug with the ocular surface
Press on the lacrimal sac
Use viscous drops, suspensions, ointments
Slow-release delivery systems
Contact lenses
Porcine collagen corneal shields

56

Why are preservatives used in drugs and what are some examples

Preservatives are used to prolong shelf life of drugs and protect the eye from infection (prevent bacterial growth)
Examples: benzalkonium chloride (BAK), chlorhexidine digluconate, polyquaternium-1, and thimerosal

57

How does BAK work?

Antibacterial action of BAK is based on the detergent property of the compound
Breaks down bacterial cell walls
The detergent property also causes the epithelium and endothelium to be susceptible to damage

58

BAK cont..

One drop of 0.01% BAK causes increase in permeability of the cornea to fluorescein
BAK also inhibits epithelial wound healing
Severe dry eye patients have increased fluorescein permeability secondary to the compromised epithelial barrier
If they use tear solutions containing BAK they risk further damage

59

What is EDTA?

used to stabilize BAK-containing formulations.
E
DTA chelates calcium, which is required for maintenance of tight junctions, and artificial tears containing EDTA may increase corneal permeability.

Therefore, when possible, ophthalmic products should be formulated without EDTA, and formulations with EDTA should be avoided by patients with dry eyes.

The preservatives BAK and chlorhexidine cause endothelial cell degeneration and corneal edema in vitro.

60

Sclera? Water content? dry weight?

Connective tissue consists of collagen, proteoglycans, fibroblasts
70% water 30% dry weight

The collagen fibers, 90% which are type I (resist tension), constitute 75% to 80% of the dry weight of the sclera.

61

What overlies sclera?

Episclera

62

Sclera mainly avascular with what exceptions?

Sclera is essentially avascular
Exceptions: superficial vessels of the episclera and the intrascleral vascular plexus

63

Posterior Sclera contain?

sclera canal and lamina cribosa (passage of the optic nerve)

Contains sites of perforation by the long and short posterior ciliary arteries, the short ciliary veins, the ciliary nerves, and the vortex veins
Tendons of recti muscles insert into the superficial sclera collagen

64

Size of sclera/ sclera thickness

95% of the total surface area of the globe
Sclera thickness decreases towards the equator and
increases near
the optic nerve

65

Diameter of scleral collagen fibrils

25-230 nm and are arranged in bundles

66

Fiber Types in Sclera?

elastic, elaunin, and oxytalan.

67

Myopia and Sclera

Form vision deprivation results in axial elongation of the ocular globe causing myopia
Also associated with myopia:
Changes in the rate of proteoglycan synthesis
Accumulation within the sclera

68

What happens to sclera as you increase in age?

Progressive degeneration of collagen and elastic fibers
Loss of GAGs
Scleral dehydration
Accumulation of lipids and calcium salts

69

Age in sclera causes?

Increase in tissue density
Sclera thinning and yellowing
Decreased sclera elasticity

70

Scleral Innervation

Stroma of the sclera is devoid of innervation, but does allow the passage of nerves
Sympathetic innervation present in monkeys

Scleral spur axons of parasympathetic origin are present in humans

Cholinergic innervations rare or absent in both monkeys and humans

71

Transscleral Delivery of Drugs

New research investigating the transscleral delivery of drugs to treat posterior segment disease
Primary mechanism: diffusion through an aqueous pathway

72

What factors control diffusion rate?

Tissue hydration
Tissue thickness
Size and volume fraction of proteoglycans present

The sclera swells least near a pH of 4

73

What alters scleral permiability?

Age, cryotherapy, and diode laser treatment do NOT alter sclera permeability, whereas surgical thinning INCREASES permeability


ange of IOP- 15 to 60 mm Hg can DECREASE sclera permeability to small molecules by half

Scleral permeability is a WEAK function of transsceral pressure

Strong function of molecular weight

74

How is permeability affected by increased molecular weight and radius?

it decreases

75

Prostglandins affect permeability?

When the sclera is exposed to various prostaglandins in organ culture there is INCREASED permeability
This causes an INCREASED expression of matrix metalloproteinases
Could be a mechanism by which prostaglandins decrease IOP when used topically

76

How can transcleral delivery be improved for large molecules?

For large molecules, transscleral deliver could be improved significantly by:

Taking advantage of thinner regions of tissue
Increasing sclera hydration
Transient modification of sclera ECM