Physiology of cornea

physiology of cornea,
biochemical composition of cornea
metabolism of cornea,
factors affecting transparency( including corneal dehydration)

1. PHYSIOLOGY OF CORNEA & FACTORS AFFECTING ITS TRANSPARENCY ANKITA MAHAPATRA 1 ST YEAR PG,OPHTHALMOLOGY VIMSAR,BURLA

2. Physiological function of Cornea To act as a powerful refracting media of fixed focus that transmits light in an orderly fashion for proper image formation. Protection of intraocular contents. Corneal reflex. Secondary function – Absorption of topically applied drugs. Wound healing after anterior segment surgery or trauma .

3. Biochemical Composition of Cornea

4. BIOCHEMICAL COMPONENTS OF CORNEA

5. SOLID COMPONENTS COLLAGEN 15 % Type I 50-55 % Type III <1% Type IV 8-10 % Type VI 25-30 % OTHER PROTEIN 5% KERATAN SULPHATE 0.7% CHONDRITIN/ DERMATAN SULPHATE 0.3% HYALURONIC ACID& SALTS 1%

6. Epithelium

7. Stroma Main bulk of cornea – 90% of total thickness

8. Extracellular Collagen Predominantly type I collagen. Type V, VI, XII, XIV also present. Fibrills or lamellae – embedded in proteoglycans matrix. Diameter and spacing between fibrils are remarkably constant. Boiling water and acid – converts into Gelatin.

9. Soluble Proteins 5% of total wet weight of Stroma Mainly consists of Albumin Immunoglobulin Glycoproteins. High level of IgA , IgG , IgM . Probably derived from serum and diffuse into the centre from limbus.

10. Proteoglycans 4-4.5% of Dry weight of Cornea. Three major fractions – Keratan Sulphate Chondroitin Sulphate Chondroitin Present in interfibrillar space of stroma. GAGs are highly hydrophilic - important role in maintenance of corneal hydration level and transparency and ‘ STROMAL SWELLING PRESSURE ’ Mucopolysaccharidosis – abnormally high GAG in stroma

11. Matrix Metalloproteinases MMP – family of enzymes that breakdown extracellular matrix components. Physiological role : Maintenance of normal corneal framework Remodelling after injury. Source : Resident cells during housekeeping function Infilltrating inflammatory cells during pathological condition. Secreted as PRO-enzyme - Activated by cleavaging of a peptide from their N-terminal end. Subtypes : MMP 1, MMP 2 , MMP 3 MMP 9

12. ENZYMES Stromal Keratocytes - Glycolytic and Kreb’s cycle enzymes Usually enzymatic activity is very low when compared to the Epithelium . ELECTROLYTES Sodium content is high whereas Potassium content is very low. Diffusible cations > Diffusible anions

13. Descemet’s Membrane Contents – Collagen ( 73%) and Glycoproteins Unique collagen structure : Lacks typical 640-A band fibrills Higher content of Glycine, Hydroxyglycine, Hydroxyproline Doesn’t contain GAGs as cementing substance. Clinico -pathological implication : Insoluble except strong acid or alkali Extremely resistant to chemical and enzymatic (Collagenase) action .

14. Endothelium Histochemical analysis shows – presence of essential metabolic enzymes i.e. Glycolysis and Kreb’s cycle .

15. Metabolism Of Cornea

16. Introduction Metabolism is mainly required to produce energy for the maintenance of Transparency Relative state of dehydration Most active part – Epithelium Second most active part - Endothelium

17. Sources of Nutrients required for metabolism

18. Minimum oxygen tension for normal corneal hydration ranges between 11-19 mm of Hg. Below this, cornea will hydrate and swell.

19. GLUCOSE Glucose is metabolized in the cornea by 3 metabolic pathway 1. Anaerobic glycolysis GLUCOSE = LACTIC ACID + 2ATP 2. Krebs cycle GLUCOSE = 36 ATP + WATER + CO2 3. Hexose monophosphate shunt GLUCOSE = NADPH + H20 + CO2 + 6ATP

20. GLUCOSE METABOLISM IN CORNEA

21. LACTIC ACID Only 12% glucose metabolised through Krebs cycle. Rest converted to lactic acid. Not metabolized by cornea Removed by diffusion into aqueous humor Accumulation results in epithelial and stromal edema . Hypoxia doubles lactic acid concentration resulting in an osmotic gradient

22. Corneal Transparency

23. Main Function of Cornea – act as a major refracting medium to form a clear retinal image of the focus object. Maintenance of Transparency : Physical/Anatomical factor Optically smooth tear film Uniform and regular arrangement of nonkeratinized epithelium Peculiar arrangement of Stromal lamellae Uniform refractive indices of all layers Avascularity Absence of myelin sheath around corneal nerves Physiological factor Relative state of dehydration

24. 1.Pre-corneal Tear Film Forms an optically smooth and homogenous layer over anterior surface of cornea. Fills up small irregularities of corneal surface. Conditions associated with pre-corneal tear film results in loss of corneal transparency.

25. 2.Corneal Epithelium Normal epithelium is transparent – homogenicity of Refractive Index. The basal cells of anterior epithelium are attached to the other neighbourhood cells i.e. laterally other basal cells and anteriorly wing cells – by DESMOSOMES and MACULAE OCCLUDENTES.

26. 3.Arrangement of Stromal Lamellae Collagen fibrills of Stroma bundled together in the form of lamellae. Arranged parallel to each other as well as to the surface. Two theories has been proposed – Maurice theory Theory of Goldman et al.

27. Maurice Theory David Maurice, Ph.D. – 1957 Cornea is transparent because the uniform collagen fibrils are arranged in a regular lattice so that the scattered light is nullified by MUTUAL INTERFERENCE .

28. Maurice Theory : A detailed Explanation Fibrills are arranged regularly in a lattice form, separated by less than a wavelength of visible light wave ( 4000 to 7000 A ). Scattered light is destroyed by – DESTRUCTIVE INTERFERENCE Electron microscopy Absence of lattice arrangement

29. Theory of Goldman et al. Described originally by Goldman and Bendeck ( 1967 ) It nullifies the need of lattice arrangement to maintain transparency by DIFFRACTION THEORY . It postulated – fibrils are small in relationship to the light and WILL NOT interfere with light tranmission unless they are larger than half of a wavelength of visible light i.e. 2000 A. Further confirmed by – ‘LAKES’ – areas devoid of collagen having dimension more than 2000A, in edematous hazy cornea, mainly found around Keratocytes.

30. 4.Avascularity of CORNEA Cornea- avascular except for small loops which invade the periphery for about 1 mm. Pathological incidents leads to corneal vascularisation : Invite defence mechanism against noxious agents. Nutrition Transport of drugs However, progressive corneal vascularisation is HARMFUL – interference with functional properties of cornea.

31. Chemical Theory Role of VIF : Meyer and Chafre Destruction of Vaso inhibitory Factors. Role of VSF : Campbell and Michaelson ( 1949 ) Used experimental corneal burn Release of VSF at the site of insult which diffuses through stroma upto the limbus and stimulates vascularisation . Corneal hypoxia may also stimulate VSF release.

32. Mechanical Theory Cogan postulated – BVS cannot invade the normal cornea because of its structural compactness Loosening of compactness of corneal stroma due to edema is mandatory for neovascularisation. Langhan postulation Neovascularisation occurs even in Fuch’s dystrophy and Aphakic bullous keratopathy Extension of edema upto limbus rarely produces vascularisation.

33. Combined Theory Demonstrated by Maurice et al.

34. Clinical correlation Cornea is immunologically privileged for keratoplasty due to avascularity, absence of lymphatics and few antigen presenting cells. Degree and depth of corneal vascularization are prognostic in keratoplasty . Deep vascularization of more than 2 quadrants is considered as high risk of graft rejection following keratoplasty

35. 5.Absence of myelin Sheath around Corneal Nerves Corneal nerves loose their myelin sheaths at 1-2 mm away from limbus. Thin and sheath-less nerves produces very little scattering of light.

36. 6.Relative State of Corneal dehydration Cornea has the highest water content than any other connective tissue in the body i.e. 78% Four Factors are responsible for keeping the water content constant

37. STROMAL SWELLING PRESSURE The pressure exerted by GAG in the corneal stroma -60mmHg, (SP) These have an anionic effect on the tissue and therefore sucking the fluid with equal negative pressure= Imbibition Pressure (IP)

38. In-vitro  Imbibition pressure (IP) = Stromal Swelling pressure (SP) In-vivo  IP changes with IOP IP = IOP – SP Therefore corneal edema is imminent when : IOP > SP In normal IOP, reduced SP SP has an interfibrillar tension causing the maintainence of normal fibril arrangement in the cornea. IOP SP IP

39. Barrier Mechanism Barrier function is exerted by both Epithelium and Endothelium. EPITHELIUM Zonulae Occludentes Desmosomes Hemidesmosomes ENDOTHELIUM Not effective as epithelial barrier Forms leaky channels allowing fluid to enter into stroma . Calcium dependent

40. Metabolic Pump It was initially suggested that water is actively transported into stroma by Fluid Pump. Later this postulation was nullified. Modern theory Water transportation occurs in association with ions – transported by different active pump mechanism  METABOLIC PUMP Proved by Temperature reversal Experiment.

41. ENDOLTHELIAL METABOLIC PUMP SYSTEM Na/K ATPase pump system Most active Active extrusion of Na Ouabain – specific ATPase inhibitor Bicarbonate dependent ATPase Present in mitochondria, not on Plasma membrane. Thiocyanate – specific inhibitor. Essential for the maintenance of the corneal thickness Carbonic Anhydrase Enzyme system Produces bicarbonate and hydrogen ions. CA inhibitors – results in corneal edema further proving its role. Na/H pump

42. It’s a complex series of metabolically dependent reactions, mainly occurring in endothelium and to some extent epithelium to maintain proper ion/fluid balance and deturgescence in the cornea.

43. Evaporation of water from the Corneal surface

44. CELLULAR FACTORS keratocytes maintain transparency by producing collagens and proteoglycans They contain enzymes involved in the assembly of stromal matrix Specific enzyme defects are associated with corneal opacification eg- mucopolysaccharidoses

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