BHE Cornea I 2024-25 Mark-up PDF

BHE See Oyster (Ch 8) Remington (Ch 2) CORNEA I DR SUZANNE HAGAN Physiology  Refracting surface  Protection of intraocular contents  Absorption of drugs  Barrier function: epithelium vs endothelium  Active pumps: Na/K ATP’ase Cornea  Transparent, avascular connective tissue with a s...

BHE See Oyster (Ch 8) Remington (Ch 2) CORNEA I DR SUZANNE HAGAN Physiology  Refracting surface  Protection of intraocular contents  Absorption of drugs  Barrier function: epithelium vs endothelium  Active pumps: Na/K ATP’ase Cornea  Transparent, avascular connective tissue with a smooth surface  Main structural barrier to infections (540-700M thick)  Eye’s principal refracting component (along with the overlying tear fluid)  Is continuous with conjunctiva & sclera  Corneal transparency is due to various physiological features (discussed in more detail in Cornea II lecture) Cornea  Provide approx 2/3rds of eye’s total refractive power  Refractive Power = 43Dioptres, Refractive Index = 1.33  Anterior surface is convex and elliptical (oval)  Horizontal diameter = 11-12mm (av. 11.7mm)  Vertical diameter= 10.6mm (~1mm less than horizontal)  Thickness in centre = 0.5mm, in periphery = 1mm  Cornea is prolate (i.e. steeper centrally, flatter peripherally)  Radius of curvature: Central cornea = 7.8mm, at posterior surface=6.5mm Gross Anatomy of Cornea  Adult horizontal diameter = 11-12mm (average = 11.7mm)  At birth, corneal diameter = 9.8mm (75-80% of human size). Fastest growth occurs during first few months of life  Central ”optical” zones approximately 4 - 5 mm in diameter  Peripheral optical zone outside pupil area  Cornea Structure, 5 layers:  Epithelium  Bowman’s membrane  Stroma  Descemet’s membrane  Endothelium The cornea has 3 main cell types: epithelial, stromal keratocytes and endothelial cells Cornea  Corneal epithelium cells = many layers  Bowman’s membrane = amorphous collagen  Stroma = collagen matrix with keratocytes  Descemet’s membrane = unstructured collagen  Corneal endothelium = cell monolayer Confocal microscopy of corneal endothelium  Corneal Epithelium  ~ 5-7 cell layers thick (about 50M thick)  Epithelial cells replaced ~ every 7 days  Comprised of flattened superficial squamous cells, intermediate (and less-flattened) wing cells and innermost cuboidal basal cells  Squamous cells’ surfaces have small projections (microplicae)  Mucin (from goblet cells) coats the microplicae and forms the innermost layer of the tear film  Tear film is important - smooths out epithelial micro-irregularities  Thus, epithelial cells are crucial in maintaining a stable tear film (& also in secreting the epithelial basement membrane)  Cross-sectional View of Corneal Epithelium Epithelial glycocalyx (mucins) - maintains ocular surface barrier function  Squamous Stratified Corneal Epithelium  Each cell type in corneal epithelium is related, because as the basal cells divide and migrate anteriorly, they change into wing cells.…which move further forward and flatten out. These become squamous cells which desquamate (are shed) into the tear film  Basal-to-squamous cell differentiation takes ~10 days  Cells of the Corneal Epithelium  Epithelium supported on a basement membrane (BM) and cells are tightly connected together  Superficial squamous cells are linked by anchoring junctions (zonula occludens or tight junctions) that prevent tear film inflow (as shown by fluorescein dye exclusion in healthy corneas)  Wing and basal cells are connected by anchoring junctions (desmosomes)  Basal cells are attached to BM by hemidesmosomes The plasma membrane of the surface epithelial cells secretes a glycocalyx component which binds mucin onto the cornea Cross-sectional View of Corneal Epithelium Intercellular Junctions of the Corneal Epithelium Intercellular junctions of the corneal (and conjunctival) epithelium are part of the 1st line of protection against pathogens and allergens. The cornea has 4 types of junctions: 1) Tight junctions (zonula occludens) These exist at different depths 2) Desmosomes of the stratified epithelia 3) Adherens junctions 4) Gap junctions  Bowman’s Layer (or Bowman’s Membrane)  Smooth, acellular, non-regenerating layer  8-15M thick and is located between the epithelium and stroma (is technically a transition zone)  Dense fibrous sheet of randomly-arranged collagen fibrils  Collagen fibrils (diameter ~20nM) are not ordered into bundles (unlike the stroma)  Helps cornea maintain its shape (rigidity) Histopathology of corneal epithelium and Bowman's Membrane  Stroma (or Substantia Propria)  At 500M, is 90% of total corneal thickness  Can regenerate  Composed of (type I) collagen fibrils (lamellae, proteoglycans), keratocytes (fibroblast-like cells) and extracellular “ground substance” (a hydrated gel of proteoglycans, PG)  Uniform collagen fibrils (~30nm diameter) run parallel to each other, forming bundles (lamellae)  Fibrils ~4% PG (i.e. PGs coat collagen fibrils)  ~ 250 lamellae are distributed throughout stroma and lie parallel to corneal surface  Adjacent lamellae lie at varying angles to one another  Transparency is due to precise organisation of the stromal fibres and the extracellular matrix (ECM)  Stroma  Periphery is thicker than centre and the collagen fibrils may change direction to run circumferentially as they approach the limbus  This highly organized network reduces forward light scatter, contributing to both the transparency and mechanical strength of cornea  Stroma  Stromal collagen fibrils = type I collagen in a complex with type V collagen (creates their unique and narrow diameter)  These complexes surrounded by specialized PGs which regulate hydration and structural properties  Keratocytes synthesise collagen and glycosaminoglycans (GAGS) and are crucial in maintaining ECM homeostasis (i.e. transparency & healing)  Most keratocytes located in ant. stroma and contain corneal crystallins (which reduce light backscatter from keratocytes, so maintain transparency)  Excessive cell death of keratocytes may results in keratoconus Ultrastructure of corneal stroma, showing orientation of collagen fibrils within lamellae Stroma- a keratocyte between stromal lamellae The collagen-keratocyte matrix of the corneal stroma  Fibrils arranged in sheets (lamellae, 200 per cornea) which are ~2M thick  ~ 4 million keratocytes in normal stroma, located mainly between lamellae = ~20,000 cells/mm3  Extend over a wide area Oyster Chapter 8 Descemet’s membrane  10-15M thick and is a latticework of collagen fibrils  Produced by endothelium  Forms the BM of endothelium  Is produced continuously, so it thickens throughout life  Ends at limbus (called Schwalbe’s line)  Endothelium  Innermost layer of cornea (5M thick)  Single layer of hexagonal cells  Cells do not divide and replicate  Cell numbers decrease with age  Slightly “leaky” barrier, allows entrance of nutrients (e.g. glucose and amino acids) from aqueous humour  Metabolic pumps continually move ions across cell membranes  Endothelium Single-cell endothelial layer with a Descemet membrane of uniform thickness (epithelial surface at top). Cells very metabolically active, lots of mitochondria  Corneal Endothelium  Cells have limited capacity to divide  Endothelial cell density (ECD) declines with age (i.e. at birth = 4000-5000 cells/mm², age 80 yrs = 1000-2000 cells/mm²)  Minimum number needed for adequate function is 400-700 cells/mm2  ECD may decline dramatically (less than 1000/mm2) after corneal surgery (or even cataract surgery) and corneal thickness can substantially increase Corneal Embryology  Epithelium = from surface ectoderm (between 5-6 weeks)  Bowman’s Membrane and Stroma = from mesenchyme  Stroma= Neural crest (7 weeks)  Endothelium = from neural crest  Descemet’s Membrane = synthesised by endothelial cells