Corneal BCH Part 2 - Dr lewis

corneal immune privilege meaning

introducing an antigen int he eye does not induce an inflammatory immune response

what is involved in the complex process of wound healing

1. interactions btw ep, stroma, nerves, inflammatory cells, and tears —→ cytokines

whats involved in cellular cross talking in wound healing

1. cytokines master regulator of corneal wound healing

2. growth factor s

3. proteases

4. neuropeptides, neurotrophins

first phase of ep wound healing

latency

describe larency phase

1. no cell movement (migration) or mitosis (24 hrs)

2. damaged ep cells release cytokines

   1. initiate wound healing

   2. attract inflmmatory cells

      1. innate inflammatory response necessary for ep wound healing

   3. cause apoptosis to keratocytes

transformation stage of latency phase

1. basal cells at edge of wound

   1. increase metabolic activity

   2. form lamellipodia and filopodia

   3. secrete fibronectin

      1. creates a provisional membrane to promote cell migration

migration phase

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

2. continues until theres a monolyaer to cover the wound

3. NO CELL MITOSIS OCCURS UNTIL THE END OF THE MIGRATION PHASE

proliferation phase

1. begins after ep wound is resurfaced w monolayer

2. cells increase in mitotic activity

3. multilayer of cells develop from original monolayer

   1. cell proliferation and differentiation

attachment phase of ep wound healing

1. reestablishment of basal cells connection to stroma

   1. regenerate BM

   2. formation of adhesion complexes

2. during this time there is susceptibility to recurrent corneal erosions

bowmans layer repair invovles the formation of _____________________

collagen scar

stromal woun dhealing phases

1. destructive phase - removal of abnormal tissue

   1. neutrophil

2. synthetic phase - synthesis of new collagen

   1. keratocytes

3. remodeling phase - slow remodeling of initial scar

stromal wound healing : stroma - ep interaction

1. cross talk

   1. ep stromal interactions involving cytokines and growth factors

2. injured ep cells (or from the tears ) release cytokines (IL - 1 alpha) which affect keratocytes

3. effects last until ep basal lamina is restored

4. quiescent keratocytes become activated fibroblasts, undergo proliferation, and migration, and repopulate the wound site

5. keratocyte migration is said to happen when the ep has resurfaced the defect

stroma woudn healing - destructive phase

1. activated keratocytes (fibroblasts) produce chemokines that attracts inflammatory immune cells

   1. inflammatory response

      1. (macrophages will digest necrotic tissue)

when the ep and stroma are damaged there is an ____________________

inflammatory response

stroma wound healing - synthetic phase

1. activated keratocytes transform into myofibroblasts

   1. highly mobile cells (synthesize intracellular a smooth muscle actin)

   2. synthesize and deposit collagen adn fibronectin

      1. lay down a provisional ECM to fill defect

2. initial scar formed

stromal wound healing - remodeling phase

1. initial scar is slowly remodeled over months up to 3-4 years

2. last phase

3. overall goal is to make the scar more transparent

desbowmans, stroma, descemets cemets membrane wound healing gives an

opacity - scar

when do we get a scar

bowmans, stroma, descemets

where is UV light absorbed and why

1. cornea —> acts as a UV filter

2. protects the lens and retina

acute exposure to _________________ and __________________ induces apoptosis of corneal ep w massive shedding of cells. this crease __________

1. UV - C

2. UV - B

3. barrier defect

UV-B, violet (400 nm), and blue (475 nm) light trigger ____________ by generating __________ which damage cells. normally this is prevented by ————-

1. oxidative stress

2. ROS

3. antioxidants

antioxidant defense mechs

1. non enzymatic

   1. ascorbic acid

2. enzymatic

   1. corneal crystallins (ALDH3A1)

general aging changes to cornea

1. decrease in corneal thickness

   1. fewer keratocytes

   2. less collagen

2. inc in thickness of Descemets mem

3. decrease in endothelial cell count

characteristis of corneal degenerations

1. often asymmetric

2. aging changs

3. often begin in peripheral cornea

4. progression is variable