Wound Healing

Full thickness skin laceration healing

• Initial inflammatory response
• Epidermis epithelialisation:
• Cell migration stimulated by fibronectin
• Cell proliferation (inhibited by chalones)
• Cell differentiation 
• Vascularisation
• Intact capillaries at wound edges send out buds of endothelial cells
• New vessels appear within first week
• Wound closure
• Macrophages and fibroblasts migrate into wound
• Macrophages: clot removal
• Fibroblasts: collagen and GAG production
• Myofibroblasts can cause wound contraction
• Scarring may affect function of the structure
• Matrix metalloproteinases produce collagen degradation

Full thickness corneal laceration

• Immediate phase:

• Descemet’s membrane and stromal collagen retract causing anterior and posterior gaping

• Fibrin plug forms from aqueous fibrinogen
• Stromal oedema
• Leukocytic phase (within 30 minutes):
• PMLs invade wound from conjunctival vessels and aqueous

• Epithelial phase (1 hour): epithelial ingrowth. Contact inhibition by healthy endothelium prevents full thickness ingrowth

• Fibroblastic phase:

• Fibroblasts are derived from invading leukocytes and stromal keratocytes in central wounds

• Produce collagen and mucopolysaccharides into matrix
• As this occurs, the epithelium retreats anteriorly
• Endothelial phase (after 24 hours):

• Endothelial sliding and mitotic/amitotic multiplication to cover the posterior aspect of the wound: filling in gaps in DM and endothelium

• Late phase (after 1 week):
• Cellular infiltrate diminishes
• Collagen fibres uniformly arranged
• Stroma and Bowman’s are replaced by scar tissue (cannot regenerate)

• Descemet’s membrane cannot regenerate either but during endothelial sliding, cells deposit secondary layers in DM

Fibroblast growth factor (FGF)

• Important role in healing
• Remodels connective tissue
• Collagenisation/wound strength

• Monocyte chemotaxis, fibroblast migration and proliferation, angiogenesis, collagenase secretion

• Conjunctival healing is similar to corneal healing (with cell sliding and proliferation) however granulation tissue can be formed due to the vasculature and lymphatics

• Sclera does not actively heal: wounds are closed by granulation tissue from the episclera and underlying uvea

• Iris can only heal if wound edges are directly apposed
• Hence PIs/iridectomies remain patent
• Ciliary body and choroid heal with granulation tissue and are replaced by scar tissue
• Lens: does not truly heal but responds to trauma with cataract formation

• Retinal healing is by gliosis (replacement of nerve cells by glial cells) principally by astrocytes and by Muller cells (fibroblasts are not native to the normal retina)

• RPE undergoes metaplasia and proliferation to form fibrous tissue
• In retinal detachment, extensive gliosis/fibrosis leads to PVR