Corneal Physiology and Clinical Applications.pdf

Corneal Physiology and Clinical Applications Karen Gil MD, MHSN Permeability of Corneal Layers • Epithelium: – Zonula occludens junctions (tight junctions) force penetration of substances through the cells – Highly lipophilic (limit absorption of hydrophilic substances) • Stroma: – Highly hydroph...

Corneal Physiology and Clinical Applications Karen Gil MD, MHSN Permeability of Corneal Layers • Epithelium: – Zonula occludens junctions (tight junctions) force penetration of substances through the cells – Highly lipophilic (limit absorption of hydrophilic substances) • Stroma: – Highly hydrophilic • Endothelium: – Highly lipophilic Nutrition of Corneal Layers • Corneal cells need nutrients, glucose, oxygen, vitamins and amino acids • The aqueous humor is the primary contributor of glucose to all corneal layers – Glucose concentration is low in tear – Glucose concentration is high in the aqueous humor • Epithelial cells: – Glucose catabolism is the principal provider of energy to epithelial cells – Obtain their glucose form the aqueous humor – Tears and limbal capillaries also provide small contribution (10%) Nutrition of Corneal Layers • Glucose is converted to pyruvate by glycolysis and can enter the Krebs cycle or the lactic acid pathway depending on the amount of oxygen present • Lactic acid can’t pass the epithelium, so pass through the stroma and endothelium to be diffuse to the aqueous humor • In corneal stress lactic acid accumulates and can produce acidosis (edema and endothelial function alteration) Epithelial glucose metabolism Glycogen Glucose-1-phosphate Glucose Glucose-6-phosphate 4 ADP Anaerobic glycolysis 4 ATP Pyruvate Lactic acid O2 26 ADP Krebs cycle 26 ATP CO2 + H2O Nutrition of Corneal Layers – During sleep, oxygen levels lower and lactic acid accumulates in the stroma (mild corneal edema in the morning upon awakening) • Stroma and Endothelium: – Obtain glucose from the aqueous humor by diffusion trough the endothelium Corneal Hydration • Is essential for corneal transparency • The tight junctions that join surface cells of the epithelium restrict the amount of fluid entering from the tear film • Fluid must be transported across the cell • the basal cells are firmly connected to each other by lateral gap junctions and desmosomes and strongly attached to underlying basal lamina by hemidesmosomes Zhi Chen et al 2018 Biomed. Mater. 13 032002 Corneal Hydration • The basal membrane (closest to the stroma) of the corneal epithelium has two transport mechanisms: – Na/K pump – Na+K+Cl- cotransporter Corneal Hydration • Na/K pump moves K+ into the epithelium and Na+ into the stroma • Creating a gradient for Na+ to move down its concentration gradient into the epithelium Corneal Hydration • The cotransporter utilizes the gradient to move K+ and Cl- into the epithelium as well • Both Cl- and K+ have their own channel to then diffuse into the tears and aqueous humor, respectively • Important: – movement of K+ into the aqueous will stimulate release of Cl- into the tears (with water following) – contributing to dehydratation of the cornea Corneal Thickness/Hydration • Corneal epithelial cells have the ability to alter corneal thickness by moving Cl- into the tears Corneal Thickness/Hydration • K+ channel has shown to respond to corneal changes in pH • Hypoxic corneas after prolong contact lens wear demonstrate higher acidity and increased thickness from swelling • The K+ channel responds moving more K+ into the aqueous, moving Cl- and water out to restore normal thickness Corneal Hydration Endothelium • Water movement between endothelium and anterior chamber follows the concentration gradient of ions • Types of transporters – Na+K+ ATPase pump (located in the BM) – Na+/K+/Cl- cotransporter – Na+/2HCO3- cotransporter • Water movement out of the endothelium is believed to be driven by the anions Cland HCO3- Corneal Hydratation Regulation 1. Barrier effect of the epithelium and endothelium 2. Normal stromal pressure 3. Electrolyte transport by the epithelium and endothelium 4. IOP 5. Water evaporation in the corneal surface Oxygen Requirements • Cornea receives oxygen primarily from the atmosphere • Secondary suppliers: – Aqueous humor – Limbal vasculature – Capillaries of the palpebral conjunctiva Oxygen Requirements • Amount of pressure in the atmosphere is 760 mmHg • 1/5 of the atmosphere is oxygen • Oxygen tension in the air is 155 mmHg • Open eye: – Partial pressure of O2 in the tears is 155 mmHg – Enough to provide oxygen to the entire cornea • Close eye: – Partial pressure of O2 is of 55 mmHg in the tears – Superior palpebral conjunctiva and limbal vasculature provide oxygen to the epithelium and anterior stroma – Posterior stroma and endothelium receive oxygen form the aqueous humor (O2 partial pressure 30-40 mmHg) Only the epithelium can store O2 Corneal Regeneration Epithelial regeneration: • Basal cells (only cells with mitosis) • Derived form limbal stem cells (Palisades of Vogt) • Migrate centripetally before dividing • Basal cells differentiate into wing cells and then in squamous cells before reaching the corneal surface • Old cells are shed • The epithelium complete replaces every 7 days Traumatic Epithelial Regeneration • If basement membrane (BM) remains intact – regeneration occurs quickly, in days • If BM damages – complete healing can take months Zhi Chen et al 2018 Biomed. Mater. 13 032002 Traumatic Epithelial Regeneration • First response of epithelium after injury is to stop basal cell mitosis • Then cells surround the defect lose their attachment to the BM as they enlarge and create an epithelial sheet in order to migrate onto the wounded area • Hemidesmosomes are then created to allow proper adhesion between the migrated cells and the BM • Once the wound is closed – rapid mitosis occur to restore corneal integrity Corneal Layers Regeneration • Epithelium and Descemet’s can regenerate • Bowman’s and Endothelium can NOT regenerate • Stroma will replace itself if damaged (scar – due to new larger collagen and less organized) CORNEA CLINICAL APPLICATIONS Astigmatism • The refracting power of the eye is not the same in all meridians • The curvature of the surface of the cornea (central 3 – 4 mm) can be determine by keratometric measurement to give a clinical assessment of the corneal contribution to astigmatism • Also lens might contribute to astigmatism Recurrent Corneal Erosion • Corneal epithelium sloughs of either continually or periodically • Due to poor attachment between the epithelium and its BM or poor attachment between the BM and underlying tissue • Can occur after incomplete healing of an abrasion (hemidesmosomes are malformed) or caused by epithelial BM dystrophy • Very painful (disruption of the dense network of sensory nerve endings in the epithelium) Keratoconus • Corneal dystrophy • Focal disruptions of BM and Bowman’s layer • Usually begins in the central cornea • The stoma degenerates and thins • The affected area projects outward in a cone shape because of the force exerted on the weakened areas by intraocular pressure • Folds occur in the posterior stoma and Descemet’s membrane Hassall-Henle bodies • Small hyaline excrescences of the posterior surface of Descemet’s membrane at the periphery of the cornea • Bulge into the anterior camber • Constantly present in adults as a common finding, its incidence increase with age Corneal Guttata • As Hassall-Henle bodies are present in the central cornea are called corneal guttate • Indicative of endothelial dysfunction • The endothelium that covers these mounds is thinned and altered • Endothelial barriers is compromised • Seen as dark areas with specular reflection with the biomicroscope Contact Lens Wear • Extended wear of contact lenses are associated: – Epithelial thinning – Stromal thinning – Decreased number of keratocytes • Pleomorfism and polymegathism have been documented after only 6 years of either rigid-gas-permeable (RGP) or soft contact lenses wear Corneal Edema • Damage of the epithelium or endothelium can cause corneal edema • Result in impaired visual acuity • Minor epithelial disruption, the edema is restricted to epithelium • Endothelial damage is more likely to cause generalized stromal edema Corneal Edema • In high pressure glaucoma, the IOP can overcome the transport activity of the endothelium and force fluid from the aqueous humor into the stoma • Increase fluid retention thickens the stroma • Changes occur in the posterior cornea • Posterior stroma and Descemet’s membrane buckle, producing vertical lines called striae Corneal Neovascularization • Secondary to oxygen deprivation • New blood vessels are produce in attempt to supply the oxygendepleted • Grow of abnormal blood vessels is termed neovascularization • Commonly seen in contact lens wearer (cornea is not receiving enough O2) more common is soft contact lenses wear • Also corneal infections can induce neovascularization Herpes Simplex Virus • HSV infection • Red eye, photophobia, tearing, decreased vision skin rash • Previous episodes • Usually unilateral • Seen as SPK, dendritic keratitis or geographic ulcer • Decrease corneal sensitivity in the involved eye