6720 - Corneal Edema and Metabolism

when does corneal edema occur?

when water content exceeds 78%, leak mechanism outweight pump function

what percent increase in hydration causes light scattering and decreased refractive function?

>5%

what two regions are affected in corneal edema?

stroma and epithelium

what curvatures are affected in corneal edema and why?

posterior curvature affected more because there is more anterior interweaving in the anterior curvature that resists expansion

bullous keratopathy

permanent corneal edema

bullous keratopathy pathogenesis

failure in endothelial pump function or damage to endothelial cells

bullous keratopathy etiologies

endothelial dystrophy (fuch's), injury, surgery, hypoxia

what forces regulated corneal hydration?

IP, SP, IOP, endothelium pump, tear evaporation/osmosis

IP

imbibition pressure

SP

stromal swelling pressure

what is imbibition pressure generated by?

negatively charged GAGs

negative imbibition pressure

draws fluid into cornea

positive imbibition pressure

water leaving stroma

normal imbibition pressure

-40 mmHg

what is imbibition pressure counteracted by?

endothelial pump function

what is IP dependent on?

water content

when does IP increase?

when water content increases

when does IP decrease?

when water content decreases

what does a negative IP value indicate?

indicates more potential imbibition

what is IP affected by?

IOP

normal swelling pressure

55 mmHg

decreased SP

increased water content

increased SP

decreased water content

what produces swelling pressure?

negative charge of GAGs repelling one another

what happens to GAGs as the cornea swells?

GAGs are further apart which reduces the repulsive force

normal IOP

15 mmHg

what is IOP regulated by?

equilibrium of aqueous production and drainage

IOP function

generates a force from anterior chamber toward endothelium which forces water into the cornea

how is IOP different from negative imbibition?

IOP pushes water through cornea while negative imbibition draws water in through GAGs

IP=IOP-SP

-40=15-55 under normal physiological conditions

imbibition pressure

force is negative indicating the direction of pressure toward the inside of the stroma

intraocular pressure

this force acts toward endothelium from aqeuous humor

swelling pressure

this force pushes outward from corneal stroma

what happens when the endothelial pump is compromised/decreased?

more water in cornea, IP increases, SP decreases

how does more evaporation affect the cornea?

draws water from cornea

how does less evaporation affect the cornea?

increase water content - edema

how does bullous keratopathy affect corneal hydration forces?

increases IP and increases SP

how does stromal edema occur?

leak exceeds pump function

how does epithelial edema occur?

IOP exceeds pump function (excess water forced between epithelial cells)

where is edema found in bullous keratopathy?

stroma and epithelium (IOP normal)

ocular hypertension and edema

elevated IOP pushes more than normal amount of water in through leaky barrier from aqueous humor, pump function can't keep up

what happens when IOP exceeds SP

pushes water out of stroma, IP becomes positive, causes epithelial edema without stromal edema

hypotony

low intraocular pressure

what happens in hypotony?

pump function disrupted, causes IOP to be 0

IOP = 0, stromal effects

stromal edema only, water being drawn into stroma via IP

IOP = 0, epithelial effects

epithelium does not have IP, no water drawn into epithelium

phthisis bulbi

shrunken and non-functional eye

forces in phthisis bulbi

IP decreases, SP increases, IOP=0, all values rapidly approach 0 as water infiltrates stroma

hypoxia

increase in anaerobic metabolism, and pH is reduced

effect of increased anaerobic metabolism on cornea

build up of lactate causes osmotic draw of water into stroma (?)

effect of decreased pH on cornea

inhibits pump function, ion transport efficiency reduced, stromal edema?

glycolysis requirements

cytoplasm, oxygen not required

TCA/oxidative phosphorylation requirements

mitochondria, requires oxygen

anaerobic glycolysis

pyruvate converted to lactate catalyzed by lactate dehydrogenase

what happens to the rate of pyruvate to lactate conversion with hypoxia?

increases

why does the cornea swell when you sleep?

hypotonic tears, hypoxic metabolism of corneal tissues

FCD

fuch's corneal dystrophy

FECD

fuch's endothelial corneal dystrophy

FCD and FECD pathogenesis

1. guttata formation

2. reduced endothelial cell density/expansion of guttata - mild edema

3. severity of edema increases

4. opacification of cornea/pain/vascularization

FCD or FECD risk factors

women, genetics, age 30-40s

Descemet's function

BM that supports endothelial cells, facilitates adhesion to stroma, supports pump function and cell viability

PNBL

posterior non-banded layer

how is descemet's membrane organized?

posterior non-banded layer, banded layer

characteristics of PNBL

increases from 2 to 10 microns, formed after birth, made of collagen type 4

characteristics of banded layer

does not increase with age, made of collagen type 8, formed during embryonic/fetal development

FCD or FECD etiology

can be caused by congenital mutation in COL8A2 which encodes for collagen type 8 protein

descemet's in FCD or FECD

becomes thicker, abnormal accumulation of collagen type 8 in PNBL, disturbed assembly of collagen type 8 in banded layer

which corneal tissue requires the greatest energy utilization?

endothelium

how does the corneal stroma use energy?

maintenance/production GAGs and collagen fibrils

how does the corneal epithelium use energy?

mitosis and migration of epithelial cells

what provides the main source of glucose for the cornea?

aqueous humor (90%)

where are glycogen stores found in the cornea?

epithelium (10%)

what is used to transport glucose into corneal cells?

GLUT channels

what do GLUT transporters allow for in the cornea?

bi-directional transport of glucose following a diffusion gradient

where are GLUT channels expressed in the cornea?

epithelial and endothelial cells

what is the main way glucose is utilized in the cornea?

anaerobic glycolysis (85%)

what are the three ways glucose is utilized in the cornea?

anaerobic glycolysis, aerobic glycolysis, oxidative phosphorylation, hexose-monophosphate shunt

where does the oxygen supply for the cornea come from?

tear film

how does oxygen diffuse through the cornea?

diffuses posteriorly through the cornea

what is glucose metabolism dependent on?

partial pressure of oxygen

what is metabolism affected by?

mitochondrial density

what is the partial pressure of oxygen at the anterior corneal surface?

155 mmHg

what is the partial pressure of oxygen at the posterior corneal surface?

25-50 mmHg

what is the glucose concentration of aqueous humor?

5mM

what is the glucose concentration of the tear film?

<0.5 mM

how does glucose concentration change across the cornea?

higher glucose concentrations posteriorly and lessens as you move anterior

how is oxygen drawn into the cornea?

diffusion gradient

how is the diffusion gradient in the cornea created?

consumption of oxygen in the cornea, difference in partial pressure of oxygen in the atmosphere vs aqueous humor

where does glycolysis occur?

cytoplasm

where does oxidative phosphorylation and TCA occur ?

mitochondria

what type of metabolism predominates in the cornea?

anaerobic metabolism

how much ATP does glycolysis yield?

2 ATP

how much ATP does TCA/Krebs yield?

2 ATP

how much ATP does oxidative phosphorylation yield?

32 ATP

how much ATP does aerobic metabolism yield?

36 ATP

how much ATP does anaerobic metabolism yield?

2ATP

reactive oxygen species

chemically reactive molecules containing oxygen, missing an electron

when are ROS created?

during mitochondrial metabolism (aerobic)

what are the specific ROS of the cornea?

ascorbic acid and ALDH3A1

what is the mitochondria distribution in the cornea?

higher density towards endothelium, lower towards epithelium