Corneal Healing and Homeostasis (M2) Flashcards
For the homeostasis of the corneal epithelial cells what is the “X” in the equation X+Y=Z?
Cell contribution due to basal cell proliferation (mitosis)
For the homeostasis of the corneal epithelial cells what is the “Y” in the equation X+Y=Z?
Cell contribution due to centripetal movement of cells from peripheral (limbus) to central cornea
For the homeostasis of the corneal epithelial cells what is the “Z” in the equation X+Y=Z?
Normal loss of cells from the corneal surface
What triggers cell loss in from the corneal epithelium?
Blinking induced, Minor abrasions, Eye rubbing
What is the rate at which cells move centripetally in the cornea?
~10-15 μm/day
How long does it take for the entire corneal epithelium to be renewed?
9-12 months
Where are the stem cells for the cornea found?
Palisades of Vogt in the limbus
What are stem cells that can give rise to all tissue cell types called? 1. What is an example of these? 2
- pluriopotent
2. embryonic stem cells
What are stem cells that can give rise to multiple cell types called? 1. What is an example of these? 2
- multipotent
2. Somatic “adult” stem cells
What are somatic (non-stem) cells that can be reprogrammed back into stem cells?
Induced pluripotent stem cells (iPSC)
Describe each of the following regarding limbal stem cells:
- mitotic activity
- type of stem cell
- differentiated?
- length of life span
- low mitotic
- multipotent
- undifferentiated when in limbal epithelium
- long life span
What is the product of asymmetric of limbal stem cells? 1. Where does this process occur? 2
- one cell remaining multipotent (LSC) and one cell differentiating to transient amplifying cells (TAC)
- basal layer
What happens to transient amplifying cells (TACs) following its differentiation?
it mitoses many times while moving centripetally
When does a TAC stop mitosing?
when moving anteriorly
What is a region that protects a stem cell population and helps maintain their multipotency? 1. What is an example of this in the eye? 2
- stem cell niche
2. epithelial thickenings in the limbus
What factors of the limbus stem cell niche aid multipotency?
- Rich melanin pigments
- Different array of basement membrane proteins than central cornea
- presence of nearby blood vessels
What do patients complain of that have limbal stem cell deficiency?
- blurry vision
- foreign-body sensation
- photophobia
- tearing
- pain
Where are stromal stem cells located?
Subadjacent to limbal basal cells
What type of stem cells are stromal stem cells? 1. What can they be differentiated into? 2
- multipotent
2. keratocytes
Where are conjunctival stem cells located?
fornical conjunctiva
What type of stem cells are conjunctival stem cells? 1. What can they be differentiated into? 2
- multipotent
2. epithelial and goblet cells
What makes conjunctival stem cells different from limbal stem cells?
express conjunctival keratins
What are the stages of epithelial wound repair?
- latent phase
- Cell migration
- Epithelial cell proliferation
What processes take place during the latent phase of epithelial wound repair? 1-6
- Tear removal of damaged cells
- Rounding and retraction of epi cells at wound edge
- Loss of surface microvilli
- Basal cells flatten and hemidesmosomal attachments between basement membrane and basal cells disappear
- extracellular matrix proteins (Fibronectin, fibrin, laminin, tenascin)
- Mitosis is inhibited
When do extracellular matrix proteins appear on the wound surface during epithelial wound repair?
within an hour
How long does the latent phase of epithelial wound repair take place?
4-6 hours
What process occurs during cell migration in epithelial wound repair?
Cellular processes extend from epithelial wound margin (lamellipodia/filopodia) assisting in cell migration
What are the cell processes that assist in cell migration in epithelial wound repair?
lamellipodia/filopodia
During cell migration in epithelial wound repair how thick is the leading edge of migrating cells?
one cell thick
During cell migration in epithelial wound repair how many sheets of epithelium migrate together?
3-6
What is the rate of cell migration in epithelial wound repair?
60-80 μm/hour
In what orientation does ell migration in epithelial wound repair take place?
centripetally
What mediate adhesion of basal cells to basement membrane in epithelial wound repair? 1. And what anchor these cells to the basement membrane (Bowman’s)? 2
- integrins
2. hemidesmosomes and anchoring filaments (Type VII collagen)
What processes occur during epithelial cell proliferation in epithelial wound repair?
- Mitosis and differentiation of transient amplifying cells (TACs) resumes and until full thickness is restored
- Superficial corneal cell tight-junctions (barrier) is re-established.
How long does epithelial cell proliferation in epithelial wound repair take place?
36 hours-several months
What happens to damaged keratocytes in stromal wound healing?
undergo apoptosis
What processes in stromal wound repair does the abrasion get covered?
epithelial migration
What are keratocytes begin to proliferate, produce little extracellular matrix, and form a region of hypercellularity between recently migrated epithelium and remaining stroma called?
hypercellular myofibroblasts
What do hypercellular myofibroblasts express?
α-smooth muscle actin
What do hypercellular myofibroblasts differentiate into?
- myofibroblasts
2. fibroblasts
What produce high levels of collagen and keratocan/lumican with keratan sulfate to form highly organized fibril structure and return transparency during stromal wound repair?
fibroblasts
What Produce high levels of collagen & hyaluronan but low levels of keratocan/lumican with keratan sulfate, resulting in fibrils that are disorganized and stroma that is opaque in stromal wound repair?
myofibroblasts
What produces interleukin 1 in stromal wound repair? 1. What does IL-1 do? 2-3
- corneal epithelial cells
- Triggers initial apoptosis of keratocytes
- upregulates enzymes which are important for remodeling collagen fibril structure
- Triggers expression of other cytokines that regulate proliferation, motility and differentiation of epithelial prolif
What does Platelet Activating Factor do in stromal wound repair?
- Induces apoptosis of keratocytes
2. delays healing to allow time for removal of damaged cells.
