Cornea 2 PDF

CORNEA II BHE Dr Suzanne Hagan See Oyster (Ch 8) and Remington (Clinical Anatomy and Physiology of the Visual System)  Cornea  Forms anterior 1/6th of eye’s outer coat  Transparent, avascular with smooth surface  Provide 2/3 of eye’s total refractive power (43D)  Must be extremely tough...

CORNEA II BHE Dr Suzanne Hagan See Oyster (Ch 8) and Remington (Clinical Anatomy and Physiology of the Visual System)  Cornea  Forms anterior 1/6th of eye’s outer coat  Transparent, avascular with smooth surface  Provide 2/3 of eye’s total refractive power (43D)  Must be extremely tough to protect the inner contents Embryonic Origin of Cornea The cornea forms from the surface ectoderm, and cells from the periocular mesenchyme migrate into the cornea giving rise to the future cornea stroma Corneal Epithelium = Surface Ectoderm Bowman’s membrane = Mesenchyme Stroma = Mesenchyme and Neural Crest Descemet’s membrane = Synthesised by endothelium Endothelium = Neural Crest Corneal Stroma Development Neural crest-derived cells invade space between developing epithelium & endothelium to produce hyaluronan-rich ECM. Cells become keratocytes, which replace hyaluronan-rich ECM with a collagen fibril/PG-rich Hassell and Birk, 2010 ECM, which is transparent. Corneal Nerve Supply The cornea is the most densely innervated structure in the human body Corneal nerve endings provide sensations of touch, pain and temperature Reflex blinking and lacrimation washes objects from cornea Innervated with sensory nerve fibres via ophthalmic (1st) division of trigeminal nerve (cranial nerve V), by way of 70–80 long ciliary nerves Most corneal nerve fibres terminate in epithelium (1 nerve per 400um2, so ~325,000) - originating from long ciliary nerve fibres running through stroma Transparency Definition: “Having the property of transmitting light without appreciable scattering, so that bodies lying beyond are seen clearly” https://www.merriam-webster.com/dictionary/transparent  Corneal Transparency The cornea transmits nearly 100% of light that enters it. The structural factors important for transparency are:  Arrangement of stromal lamellae, i.e. small diameter of collagen fibrils and regulation of spacing (= reduced backscatter of light)  Uniform arrangement of epithelium  Avascularity  Relative state of hydration (Keratocytes also have a role, via ECM regulation) Stroma  Periphery thicker than centre  Highly organised network which reduces forward light scatter, contributing to cornea’s transparency & mechanical strength Biochemical Composition  H20 = 78% (higher than corneal epithelium, which is 70%)  Collagen =15%  Other proteins = 5%  Salts  Corneal Transparency - Stroma In corneal pathologies, changes in 1 or more layers can lead to increased light scattering and transparency loss  The stroma has 3 main components: collagens, proteoglycans (PGs) and keratocytes  Collagen is laid down within lamellae  Are ~ 250 lamellae in central corneal stroma and their packing density is higher in anterior lamella than in the posterior ones. Posterior lamellae (in central cornea) are more hydrated Thus posterior stroma can swell more easily than anterior  Stroma - lamellae  Bulk of corneal thickness  Can regenerate  Contains collagen fibrils (30nm in diameter, mainly type I) and keratocytes  Corneal collagen fibrils = narrower than in other body connective tissues  Narrow diameter = Crucial factor for transparency  Collagen fibrils are embedded in matrix “gel” (PGs that coat collagen), which maintains transparency by regulating H20 content  Stromal lamellae arrangement minimises light scattering, permitting transparency Thus, transparency is due to precise organisation/hydration of stromal fibrils (+PGs) and ECM  Fibril organisation and transparency  Fibrils = uniform lattice pattern  Interfibrillar spacing = 50-62nm (smaller than wavelength of light)  Stroma: Keratocytes  Stromal cells are Keratocytes which have compact and transparent cell body (= minimizes cell’s surface area, so reduces light scattering)  Keratocyes maintain the ECM turnover, synthesising collagen and PGs  So these cells are vital in maintaining corneal homeostasis (i.e. transparency and healing)  Most keratocytes are located in anterior stroma and contain corneal crystallins, which reduce light backscatter (maintain transparency)  Excessive cell death of keratocytes may result in Keratoconus  Transparency - hydration  Relative state of hydration: Active transport of electrolytes out of endothelium. Water follows (Na-K ATPase)  Relative hydration of cornea is controlled by endothelium and epithelium via barrier function and active pumping mechanisms  Corneal Hydration Normal cornea maintains a state of relative dehydration (~78% H20) needed for transparency. This is maintained by: 1. Stromal swelling pressure and IOP (factors that draw H20) 2. Barrier functions of epithelium and endothelium (factors that prevent H20 flow in cornea) 3. Active pumping action of endothelium (H20 and ion transport) NA/K - activated ATPase pump system  Endothelium is more active than epithelium  Pumps located in endothelial cell membranes  Pump causes extrusion of Na+ and H20 from stroma (thus maintaining transparency)  Endothelium pump mechanism  Primary function of endothelium is permit “leakage” of solutes and nutrients from aqueous humour to more anterior corneal layers (as well as pumping H20 in the opposite direction = from stroma to aqueous)  This dual purpose = "pump-leak hypothesis“  As cornea is avascular, nutrition of corneal epithelium/stromal keratocytes/corneal endothelium must arise via diffusion of glucose (and other solutes) from the aqueous humour, across the endothelium  Then, the endothelium transports H20 from the stromal-facing surface to the aqueous-facing surface (via various active & passive ion exchangers)  Na+/K+ATPase and carbonic anhydrase are crucial to this process. Bicarbonate ions formed by the action of carbonic anhydrase are translocated across the cell membrane, allowing H 0 to passively follow  Corneal Endothelial Pump The endothelium actively dehydrates the stroma through the action of water pumps in the endothelial cells. Controls ion movement (osmotic gradient), endothelium draws water from stroma Pumps: -Na+/K+ -ATPase (maintains Na gradient, so promotes bicarbonate production) -Bicarbonate-dependent-ATPase -Water selective channels Therefore, the Corneal endothelium responsible for maintaining the hydration of cornea, via active transport of various ions Transparency  If cornea swells much above its physiological hydration, it scatters light and loses transparency  Endothelium-based pumping mechanism maintains corneal hydration (which would otherwise increase, due to stromal gel pressure)  If pumping mechanism fails and cornea swells, regions without collagen fibrils impair corneal transparency  Causes of oedema Corneal Oedema CL wear Glaucoma Ageing Ocular surgery (i.e.cataract) Uveitis Dysfunctional endothelial pumping mechanism Corneal Oedema Oedema may also be caused by: Temperature change pH Hypoxia (low O2 levels) Trauma Infection Corneal Oedema Normal Oedema Swollen cornea showing collagen fibrils and areas without fibrils (called “lakes”). Lakes spoil interference necessary for transparency  Hydration versus transparency of Cornea and Scleral Stroma  Normal cornea = ~78% water, i.e. more hydrated than scleral stroma  Corneal stroma increases in thickness as wet mass increases (so hydration increases as does thickness, but with reduction in transparency)  Deeper layers are more strictly organised than superficial layers. This variation accounts for the differences in response to corneal oedema  Swelling Properties of Cornea Versus Sclera  Stroma composed of same size fibrils, with a higher % of PGs (compared to scleral stroma which is composed of variable- sized collagen fibrils and a low % of PGs)  Therefore, corneal stroma swells 2.5X more than scleral stroma when immersed in physiological saline (NaCl).… and can lose some of its transparency as it swells (looks opaque) See also https://oscb-berlin.org/deeper-insight-into-the-cornea/  Corneal Thickness  Corneal thickness is measured by a pachymeter  Average central corneal thickness (CCT) is ~ 0.535 mm (Oyster suggests 0.5mm). Peripheral corneal thickness ~ 0.7 mm  CCT can increase by 10% with CL wear, and by 50% following surgery (corneal or cataract)  Corneal Thickness and Curvature  Average anterior corneal curvature ~ 7.8 mm (by keratometer)  Average posterior corneal curvature ~ 6.5 mm by ORBSCAN or PENTACAM topographers  Blood Supply  Avascular  Small loops derived from anterior ciliary vessels invade periphery for ~1mm  Loops not actually in cornea but in subconjunctival tissue  No lymphatics Corneal Nutrition Cornea needs energy for metabolism, for maintaining transparency and for dehydration Energy provided glucose, amino acids and vitamins (from aqueous, via leaky endothelium) O2 comes mainly from atmosphere (via tear film), followed by aqueous humour (and limbal capillaries)  Prof Connon, Newcastle University Video link: https://www.youtube.com/watch?v=7xoRe2OFNnI Other researchers are also developing 3D cornea models Assembly of the different layers that compose a corneal tissue model. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754119/  August 2022:Indian clinician-scientist team Review on 3D printing in ophthalmology https://pubmed.ncbi.nlm.nih.g ov/35952803/ (full paper in Module Info of GCU Learn) https://www.tctmagazine.com/additive-manufacturing-3d-printing-news/latest-additive- manufacturing-3d-printing-news/3d-printed-human-cornea-developed-by-team-of-clinicians-and- scientists/