Oc Phys Exam 2 - Corneal Biochem

what are the key functions of the cornea?

transparency

structural support

biodefense

what structural features of the cornea contribute to its function?

smooth anterior surface

intact epithelium and endothelium

normal corneal contour - collagen

clarity of tissue

normal thickness

avascularity

what is the anterior barrier of the cornea?

zonula occludens - tight junctions

superficial squamous cells

what does glycocalyx contain?

membrane- anchored mucins

what produces glycocalyx?

superficial epithelial cells and goblet cells

what is the most richly innervated tissue of the body?

cornea

nerves directly maintain the health of the epithelium through ____ factors

trophic

list the steps of cell replacement

daughter cells of stem cells migrate onto the cornea - become transient amplifying cell - differentiate - become basal cells - proliferate into wing cells - differentiate into superficial squamous cells

which cells of the cornea are terminally differentiated?

superficial squamous cells

which cells of the cornea are post-mitotic?

wing cells

how does bowman's layer anchor?

type VII collagen anchoring fibrils:

basal lamina attached to anchoring plaques in bowman's layer

strongly attached to stroma

what is the main function of bowman's layer?

protects against shearing damage

what is the main function of the stroma?

transparency

mechanical strength

maintains corneal curvature

which section of stroma is more resistant to change in stromal hydration?

anterior

what are the contents of stroma?

78% water

15% collagen

7% proteins/cells

what surrounds each fibrin in collagen?

proteoglycans

which section of stroma has more shear resistance?

anterior 1/3

which section of stroma has more tensile strength?

posterior 2/3

what are the main functions of proteoglycans?

spacing of collagen

GAGS: highly negative charge - control hydration

act as a pressure exerting gel

what are the main functions of karatocytes?

synthesize collagen, ECM and crystallins

transparency

wound healing

what are the main functions of crystallins?

cellular transparency

antioxidants to reduce UV damage

what are the second most metabolically active cells in the eye?

endothelial cells

why are leaky tight junctions important in the endothelium?

allows paracellular transport of nutrients from aqueous to cornea

but not too leaky bc maintain a relatively dehydrated state

what is the main supply of oxygen to the cornea?

tear film reflects atmospheric oxygen

when eye is closed what is the oxygen source?

less o2 than open eye but gets 2/3 from eyelid blood supply

what provides glucose and oxygen to the posterior cornea?

aqueous

why is the corneal endothelium so metabolically active?

ionic pump mechanisms

what happens with corneal hypoxia?

increased lactate accumulation causes corneal swelling

most light scattering in cornea is due to what?

cells, not collagen fibrils

how is transparency of the cornea maintained?

1. barrier function of epithelium and endothelium

2. size and arrangement of collagen fibrils (small and close)

3. uniform index of refraction (crystallins)

4. relative dehydration of the cornea (78%)

how do GAGs account for swelling tendency?

negatively charged, repel each other, and cause expansive force

attract Na+, absorbs water, intraocular pressure

why does damage to endothelial cells cause more swelling than damage to epithelial cells?

due to IOP

tear film hypertonicity causes what?

dehydration

what does the epithelial pump do?

Na+/2Cl- co transport

pumps Cl- into tears

what is the most important pump in corneal dehydration?

Endothelial pump

Na+ and HCO3- pumped out of cornea, pulls water out of stroma

the state of epithelial hydration is mainly dictated by what?

IOP

Do fibrils swell?

NO, the spacing between the fibrils increases

which section of the cornea accumulates water more easily?

posterior 2/3

stroma swells in ________ direction

posterior

can create folds in descemet's membrane

what is corneal immune priveilege?

introduction of an antigen into the eye does not induce an immune response

wound repair is a complex process that involves interaction bw epithelium, stroma, nerves, inflammatory cells, tears and what?

cytokines

what is the master regulator of corneal wound healing?

cytokines

list all substances participate in corneal wound healing cellular cross talk?

cytokines, growth factors, proteases, neuropeptides, neurotrophins, MG-53 protein

what is the latency phase of epithelial wound healing?

no cell movement or mitosis in the epithelium

damaged cells release cytokines that initiate wound healing

inflammatory response necessary

what is the transformation in the latency phase of epithelial wound healing?

basal cells at edge of wound increase metabolic activity and form lamellipodia and filopodia

secrete fibronectin providing a provisional membrane

what is the migration phase of epithelial wound healing?

sheets of basal cells at edge of wound are flattened with extended filopodia and are pulled across the defect

continue until monolayer covers wound

no mitosis until the end of the migration phase

what is the proliferative phase of epithelial wound healing?

cells begin to divide after basal monolayer covers wound

multilayers develop - cell proliferation and differentiation (into wing cells and squamous cells)

what is the attachment phase of epithelial wound healing?

begins once epithelium has stratified

reattach basal cell epithelium to bowmans layer and anterior stroma under wound

why must new attachment in wound healing be similar to normal adhesion?

if not, pt susceptible to recurrent corneal erosions

what happens if bowmans layer is damaged?

formation of collagen scar

what are the 3 phases of stromal wound healing?

destruction - neutrophils remove abnormal tissue

synthetic - keratocytes synthesize new collagen

remodeling - of the initial scar

the cross talk bw the stroma and epithelium primarily involve...

cytokines (which affect keratocytes) and growth factor

what happens when quiescent keratocytes are activated?

they become fibroblasts, undergo proliferation and migration, and repopulate the wound site

migration occurs when the epithelium has resurfaced the cornea in front of the stromal defect

when the stroma is damaged, what is the inflammatory response?

1. activated keratocytes produce chemokines to attract inflammatory immune cells

2. neutrophils migrate in within 3-5h

3. macrophages arrive later and phagocytize debris

activated keratocytes transform into what?

myofibroblasts: highly mobil cells that synthesize collagen and fibronectin. lay down a provisional ECM to form the initial scar

what is the last phase of stromal wound healing?

remodeling phase: months up to 3-4 years

make scar more transparent

what are the 3 damages that result in a scar?

bowmans, stroma, descemets

what happens with wound healing of endothelium?

no mitosis, they simply spread over defective area

the _______ is where UV light is absorbed which protects lens and retina.

cornea

acute exposure to UV-C and UV-B induces what?

1. apoptosis of corneal epithelium with massive shedding of cells which creates a barrier defect - SPK

2. ROS which damage cells - usually prevented by antioxidants

what are the antioxidants in the cornea?

Ascorbic acid

corneal crystallins (ALDH3A1)

what are the aging changes in the cornea?

decrease in corneal thickness - loss of keratocytes

increase in thickness of descemet's

decrease in endothelial cell count

what are the basic characteristics of corneal degenerations?

asymmetric

aging changes

begin in peripheral cornea

variable progression