cornea- Dr. Mokhlesur Rahman (Anatomy and Physiology).pptx

Anatomy of cornea, Physiology of cornea

1. Anatomy and Physiology of CORNEA Presented by Prof. Dr. Md. Mokhlesur Rahman.

2. CORNEA: What is it actually??? The cornea is a transparent, avascular , watchglass like structure. It forms anterior one- sixth of the outer fibrous coat of the eyeball. To meet the diverse functional demands cornea must be Transparent Refract light Contain the IOP Provide a protective interface

3. DIMENSIONS Anterior surface of cornea is elliptical with horizontal diameter-11.75mm Vertical diameter is 11mm Posterior surface of cornea is circular with diameter of 11.5mm

4. Thickness of cornea in centre is about 0.52mm while at periphery it is 0.921mm Radius of curvature Central part, which is of 5mm, forms the powerful refracting surface of the eye. The ant. & post. curvature of the central part of cornea are 7.8 & 6.5 mm respectively. Refractive power of the ant. Surface: +48D; Post surface: -5D. Therefore, net refractive power of cornea is +43D Refractive index of cornea is 1.37 DIMENSIONS

5. EMBRYONIC ORIGIN OF CORNEA Corneal epithelium – surface ectoderm Bowman’s membrane – Mesenchyme Stroma – Mesenchyme & Neural crest Desment’s membrane – synthesized by endothelium Endothelium – Neural crest cells

6. CONGENITAL ANOMALIES Megalocornea is labelled when the horizontal diameter of cornea is of adult size at birth or 13 mm or greater after the age of 2 years. Differential diagnosis 1. Buphthalmos .- In this condition IOP is raised and the eyeball is enlarged as a whole. 2. Keratoglobus .- In this condition, there is thinning and excessive protrusion of cornea, which seems enlarged; but its diameter is usually normal.

7. buphthalmos keratoglobus

8. Microcornea In microcornea , the horizontal diameter is less than 10 mm since birth.

9. Layers of Cornea Epithelium Bowman’s membrane Substantia Propria (corneal stroma ) Dua’s layer Descemet’s membrane Endothelium

10. Layers of Cornea: Histology

11. Epithelium Epithelium is made of stratified squamous non-keratinized type & becomes continous with epithelial layer of bulbar conjunctiva at the limbus . It is about 50-90µm thick, represents 10% of corneal thickness & consists of 5-7 layers of cells. The deepest (basal) layer columnar cells Mid 2-3 layers: wing or umbrella cells Most superficial 2 layers: flattened cells The entire epithelium is replaced in a period of 6-8 days via mitotic activity of basal cells.

12. Important features of various layers of epithelium Basal layer Basal layer comprises of tall columnar polygonal shaped cells arranged in a palisade like manner on a basement membrane, having density of about 6000cells/mm 2 It forms the germinal layer of the epithelium & undergoes mitosis to produce daughter cells which continously migrate anteriorly into the wing cell layer. The mitochondria are small & few suggesting low aerobic oxidation & more dependence on the pentose shunt for metabolism.

13. The basal cells are firmly joined laterally to the other basal cells & anteriorly to the wing cells by desmosomes & zonula occludens . Function of these tight intercellular junctions: Epithelium’s transparency Resistance to flow of water, glucose & electrolytes Barrier function to inhibit entrance of pathogens.

14. Limbal stem cells The basal cells of limbal area form limbal stem cells . Epithelium stem cells are the undifferentiated pluripotent stem cells found in the limbal basal epithelium of palisades of vogt . They are the source of new corneal epithelium.

15. Basal lamina ( basement membrane of the basal cells) Anteriorly firm adhesions are formed between basal epithelial cells & the basal cells by the filaments extending from the latter called as adhesion complex, made up of hemidesmosomes & type 7 collagen fibrils Applied of adhesion complex : If they are abnormal it leads to recurrent erosions & epithelial defects.eg. In DM Holds epithelium to basement membrane & its stroma , so its defect is seen as epidermolysis bullosa , can lead to bullae formation Filamentary keratitis is a condition in which strands (“filaments”) composed of degenerated epithelial cells and mucus develop on and adhere to the corneal surface causing pain and foreign body sensation.eg. Dry eye

16. Wing cells They are attached with basal cells posteriorly & other wing cells laterally & anteriorly via tight junctions

17. Flattened cells They have numerous zonula occludentes & desmosomes than any other layer The anterior cell wall of most superficial layer consist of microvilli (which contain glycocalyx ) which plays an important role in tear film stability Superficial cell layer has junctional complexes formed with laterally adjacent stem cells which maintain the barrier function of the epithelium. A clinical test to determine whether the barrier is intact uses dyes such as fluorescin . If there is epithelial defect it stains positive which is seen as green colored defect in blue filter.,which is not so if there is no epithelial defect.

18. Bowman’s membrane This layer has acellular mass of condensed collagen fibrils. It can’t regenerate & replaced by coarse scar tissue Compact arrangement of collagen gives it great strength and relatively resistant to trauma both mechanical and infective Function it acts as a smooth base for epithelium uniformity thus helping in refraction

19. Stroma ( substantia propria ) It consists of collagen fibrils & stromal cells embedded in hydrated matrix of proteoglycans (ground substance) The parallel arrangement of the central corneal fibrils extends to the periphery where the fibrils adopt a concentric configuration to form a ‘weave ‘ at the limbus . This imparts considerable strength to the peripheral cornea & permits it to maintain its curvature, & thus its optical properties. STROMA

20. The lamellae are arranged in many layers. In each layer they are not only parallel to each other but also to the corneal plane and become continuous with scleral lamellae at the limbus . The alternating layers of lamellae are at right angle to each other. Among the lamellae are present keratocytes , wandering macrophages, histiocytes and a few leucocytes. Function It provides rigid frame to maintain IOP

21. DUA’S LAYER Discovered by Dr. Harminder Dua in 2013 composed of collagen type 1primarily,4 & 6,proteoglycans & lacks keratocytes 15 μ m thick Between corneal stroma and Descemet’s membrane Doesn’t extend to periphery

22. DESCEMET’S MEMBRANE Made of collagen & glycoprotein It can regenerate Posterior 2/3rd formed after birth and consist of a homogeneous fibrogranular material -The zone adjoining the endothelium is the most recently formed -Modified hemidesmosomes attachment present in between DM & endothelium - Resistant to chemical agents, trauma ,infection & pathological process.

23. Hassel- Henle warts: -It is the peripheral excrescences produced by focal overproduction of basal lamina like material in aging cornea -No clinical abnormality in corneal function Descemet’s warts of central cornea is called Cornea Guttata,which shows ‘Beaten metal’ appearance it is associated with increased permiability of endothelium

24. Fig.: Cornea Guttata in Fuchs’ dystrophy

25. ENDOTHELIUM Single layer of flat polygonal cells Endothelial cells maintain corneal deturgescence throughout life by pumping excess fluid out of the stroma . The young adult cell density is about 3000 cells/mm2 . The number of cells decreases at about 0.6% per year and neighbouring cells enlarge to fill the space; the cells cannot regenerate. At a density of about 500 cells/mm2 corneal oedema develops and transparency is impaired.

26. BLOOD SUPPLY Small loops derived from the anterior ciliary vessels invade cornea’s periphery for about 1 mm & provide nourishment

27. Nerve Supply Trigeminal nerve Ophthalmic division Nasociliary nerve Long ciliary nerve Pericorneal plexus Stromal plexus Sub epithelial plexus Supplies all over epithelial layers Conjunctival nerve Looses sheath of shwann

28. METABOLISM OF CORNEA SOURCES OF NUTRIENTS: Oxygen - epithelium derives O2 mainly from tear film(an active process),& from limbal capillaries Epithelium consumes O2 ten times greater than stroma . Endothelium derives its O2 mainly from aqueous

29. GLUCOSE: The respiratory quotient of cornea is 1 suggesting glucose metabolism is the prime energy source. Aqueous humor is the main source of glucose for endothelium,stroma & epithelium. AMINO ACIDS: Its continuous supply is required to allow synthesis of protiens required for the constant shedding & replacement of the epithelial cells of the cornea Main source: Aqueous humor by passive diffusion

30. METABOLIC PATHWAYS GLYCOLYSIS: It is ANAEROBIC process Through glycolysis ,glucose is broken down to lactic acid with generation of 2 ATP/molecule of glucose broken. HEXOSE MONOPHOSPHATE OR PENTOSE SHUNT: occurs both in hypoxic & normoxic conditions ,produces NADPH & Ribose 5-p which is used in lipid synthesis by corneal epithelium & nucleic acid synthesis KREBS/TCA/CITRIC ACID CYCLE in aerobic conditions pyruvic acid is oxidized to yield CO2, H2O,& 36 ATP

31. CORNEAL TRANSPARENCY The cornea transmits 100% of the light that enters it . Transparency is achieved by: ARRANGEMENT OF STROMAL LAMELLAE 2 THEORIES : Maurice theory : the cornea is transparent because the uniform collagen fibrils are arranged in regular lattice so that scattered light is destroyed by the mutual interference. The fibrils are arranged such that they have less diameter (275-300A)̊& separated by less than a wavelength of light (4000 to 7000A)

32. b)THEORY OF GOLDMANN et al. The cornea is transparent because the fibrils are small in relationship to the light & donot interfere with light transmission unless they are larger than 1½ a wavelength of light(2000A).

33. Other factors responsible for corneal transparency: expression of corneal crystallins in keratocytes to minimize light scatter corneal avascularity unmyelinated nerve fibres relative deturgescence state of normal cornea corneal epithelium & tear film epithelial non keratinization uniform & regular arrangement of corneal epithelium junctions between cells & its compactness & tear film also maintain a homogenicity of its refractive index

34. FACTORS AFFECTING CORNEAL HYDRATION: STROMAL SWELLING PRESSURE : (60mmhg) it is imparted by GAGs of the corneal stroma which act like a sponge. The electrostatic repulsion of the anionic charges on the GAGs expands the tissue,sucking in the fluid with equal but negative pressure called imbibition pressure(IP) IP is reduced by the IOP , i.e.IP =IOP-SP(swelling pressure) or IP= 17-60 =-43mmhg The cornea thus has a swelling pressure & a metabolic pump designed to maintain it.

35. Barrier function of endothelium & epithelium Hydration control by active pump mechanisms present on endothelium which are: Na+/K+ - ATPase pump –which mediates extrusion of Na+ into aqueous bicarbonate dependent ATPase:extrusion of bicarbonate ion into aqueous carbonic anhydrase enzyme Na+/H+ pump 4)Evaporation of water from corneal surface 5)IOP: when IOP exceeds the SP of corneal stroma epithelial edema will occur

36. DRUG PERMEABILITY ACROSS CORNEA LIPID & WATER SOLUBILITY OF DRUG: Epithelium & endothlium are lipophilic Stroma:hydrophilic Thus a drug should be amphipathic molecular size,weight ,& conc. Of drug Molecular size: <4 A are readily permitted Molecular weight :<100 can easily pass through & those with more than 500 can’t

37. IONIC FORM OF DRUGS : Epithilium permits non ionized drugs Stroma : ionized drugs Thus a drug should exist in both forms Thus, fluorescin a negatively charged ion can’t penetrate intact epithelium. Ph of the solution :<4 &>10 permeability TONICITY OF SOLUTION : hypotonicity permeability DRUG PERMEABILITY ACROSS CORNEA

38. SURFACE ACTIVE AGENTS : surface tension reducing agents Increase corneal wetting drug absorption PRO-DRUG FORM: they are lipophilic hence easily pass through epithilium & then converted to active form which easily passses through stroma eg.dipivefrine

39. WOUND HEALING EPITHELIUM: The XYZ hypothesis: Thoft R. and Friend J. (1983) proposed on the basis of experimental evidence that both limbal basal and corneal basal cells are the source for corneal epithelial cells, and there is a balance among division, migration & shedding.

40. The corneal epithelium is maintained by a balance among sloughing (Z) of cells from the corneal surface, cell division (X) in the basal layer and renewal of basal cells by centripetal migration (Y) of new basal cells originating from the limbal stem cells.

41. Repair of corneal epithelial injury like abrasion follows a distinctive sequence of events - Injury (abrasion) Cells at wound edge retract, thicken and lose attachment Travel in an amoeboid movement to cover the defect Cells at wound edge ruffle and send out filopodia and lamellipodia towards the center of wound

42. Migration process is halted by contact inhibition They then anchor and Mitosis resumes to re-establish epithelial thickness Surface tight junctions re- establised Adhesion with Bowman’s layer within 7 days (if basal lamina intact) •The healing process occurs rapidly, rate of cell migration is 60 – 80 μm /hr

43. Stromal repair: Repair of stroma after small injuries involves: Keratocytes activation Migration & transformation into fibroblasts Production of scar tissue Initial fibrils are large & irregular

44. Remodelling of scar tissue occurs, it ensues – 1.Thinning of fibrils 2.Reformation of lamellae over months 3.Increase in transparency Larger wounds provoke rapid vascular response and leaving vascularised scar along with lymphatic channels

45. Repair of Descemet’s layer : After traumatic interuption of DM (Path./Mech.) Endothelium spread its cells to resurface the defect Synthesis of fresh basal lamina which is structurally identical to normal descemet’s layer

46. Endothelial Repair : Physical & chemical damage to endothelium results in loss of cells Neighboring cells move over to fill the gap by sliding process and enlargement of cells occur Thus, after injury, the endothelial cell density falls, the cell area increases and the cell height decreases

47. The degree of scarring from healing varies. If the wound is very superficial and involves the epithelium only, it heals without leaving any opacity behind. When wound involves Bowman's membrane and few superficial stromal lamellae, the resultant scar is called a ' nebula '. Macula and leucoma result after healing of ulcers involving up to one-third and more than that of corneal stroma , respectively.

48. Presenter: Prof. Dr. Md. Mokhlesur Rahman Head pf the department, Department of Ophthalmology Rangpur Medical College