Anatomy and physiology of Lens. power point

Ophthalmology basics

1. Anatomy and Physiology of Lens

2. Lens Basics Embryology Anatomy

3. Lens: Embryology

4. Tunica vasculosa lentis Posterior pupillary membrane Anterior pupillary membrane Completely developed at 9 weeks of gestation Regress by 8 th month of gestation in an orderly mechanism of apoptosis Mittendorf dots (remnant at posterior surface of lens) and Bergmeister papillae (remnant at optic disc)

5. Lens: Congenital Anomalies Congenital Aphakia Congenital aphakia Can be primary ( failure of development of lens placode) or secondary (absorption of developing lens) Lens coloboma Lens Coloboma Abnormality of lens shape True coloboma of lens probably does not exist Coloboma of zonules results in deformed equator of lens simulating lens coloboma

6. Lenticonus Lenticonus Localized cone shaped deformation of lens surface Can be anterior or posterior Anterior lenticonus: Alport syndrome, Spina bifida, Waardenburg syndrome Posterior lenticonus : Lowe syndrome Posterior Lenticonus Anterior Lenticonus

7. Microspherophakia Small and spherical lens Entire lens equator is visible through slit lamp in dilated pupil Primary: isolated hereditary abnormality Secondary: Weill Marchesani syndrome, Marfan, Alport, Lowe, Congenital Rubella

8. Mittendorf dots Mittendorf Dots Remnant of posterior pupillary membrane of Tunica vasculosa lentis Inferonasal to posterior pole of lens Epicapsular Star Star shaped distribution of golden yellow or brown flecks On central anterior capsule of lens

9. Marfan syndrome Ectopia lentis Subluxation of lens Can be congenitally present due to Aniridia Familial Marfan syndrome: superotemporal Homocysteinuria : inferonasal

10. Lens: Congenital Cataract Infantile Visible at birth or before 1year of age Severe loss of vision (interferes with development of foveal fixation) Developmental Visible after 1 year of age Minimal loss of vision Blue dot cataract Most common congenital cataract overall Most common Developmental cataract Downs syndrome

11. Lamellar/Zonular Most common infantile cataract Presents as Opacity in fetal nucleus Spoke like opacities called Riders Posterior polar cataract with onion peel/ whorled appearance Congenital rubella syndrome, vitamin D deficiency, familial (AD)

12. Lens: Features Characteristics : Transparent, biconvex, crystalline Location : B etween iris and vitreous, in patellar fossa [saucer shaped depression ] Wiegert’s ligament, Berger’s Space Shape : Asymmetric oblate spheroid Refractive index : 1.39 ; nucleus(1.42) > cortex(1.38) Consistency : nucleus-harder, cortex- softer Weight : 65mg(birth)  125mg(1 st yr )  2.8mg/year increase till 150mg (1 st decade)  slow rate increase  260mg (70-80yrs)

13. Colour : Transparent ( infants) Colourless (young adults) Yellowish tinge ( 30 years) Amber (old)

14. Lens, Dimensions Surface : Anterior surface (radius = 10mm) is less convex than posterior surface (radius= 6mm) Pole : Centre of anterior and posterior surface Equator : point where two surfaces meet Equatorial diameter : 6.5mm (birth), 9-10mm (second decade), then constant Axial thickness(AP diameter) : 3.5mm (birth), 5mm (extreme of age)

15. Lens: Structure 3 Parts 1 2 3

16. Lens : 01. Capsule Thin, transparent, hyaline collagenous membrane Surrounds lens completely Highly elastic Produced continuously throughout life, by basal area of lens epi anteriorly and elongated fibres posteriorly PAS positive; lamellar appearance Type 4 collagen and GAGs Thickest basement membrane in the body Chemical and Antigenic similarity with BM of kidney, lungs, spleen, blood vessels

17. True exfoliation Superficial lamella of capsule splits off from the deeper layer, forming one or more sheets that curl into anterior chamber Due to prolonged exposure to infrared radiation (glass and steel workers); nowadays more frequently seen as idiopathic senile change/ due to heat exposure or trauma Pseudoexfoliation Deposition of fibrillo-granular white fluffy materials over cornea, iris, lens, trabecular meshwork etc (limited to anterior segment of eye) Pseudoexfoliation syndrome (PEX syndrome)

18. Lens: Capsule Anterior > Posterior Equator > Pole Thinnest at Posterior pole

19. Lens: 02. Anterior lens epithelium Single layer cuboidal nucleated epithelium Deep to anterior capsule Organelles of typical epi cell + cytoskeletal elements (actin, vimentin, tuberlin ) All metabolic, synthetic and transport processes of lens In equatorial region, these cells are columnar which actively divide and synthesize new lens fibres throughout life No posterior epithelium

20. Lens Epithelium: Zones Central Cuboidal cells which mitose only in response to injurious insults Metaplasia myofibroblast like cells ASC cataract ( eg : shield cataract in atopic dermatitis) Germinative Columnar cells, pre equatorial Actively dividing  new cells migrate posteriorly lens fibres Extremely susceptible to irradiation Dysplasia  PSC cataract ( eg : radiation, myotonic dystrophy, NF2) Intermediate Cylindrical cells which occasionally mitose

21. Shield cataract ASC cataract seen in Atopic dermatitis Christmas tree cataract PSC cataract seen in Myotonic dystrophy

22. Lens Epithelium: Features Highest metabolic rate Well characterized cytoskeletal network – actin, vimentin, spectrin, microtubules, α-actinin and myosin Lateral membrane lacks tight junction Apical membrane of lens epithelium interfaces with apical membranes of elongating fibre cells forming epithelial fibre cell interface [EFI]  characterized by transcytotic events Na-K ATPase and acid phosphatase on apico -lateral membrane

23. Lens: 03. Lens Fibre/ Substance Synthesized by equatorial region of anterior epithelium New (superficial) lens fibres are laid on older (deeper) fibres As the new fibres are laid down, the nuclei are shifted anteriorly. These anteriorly shifted nuclei form a line convex forward at equator known as Lens/nuclear bow

24. Lens Fibre: Structure Hexagonal in cross section; bound together by ground substance Interlocking processes(ball-and-socket & tongue-and-groove interdigitations) in between cells with zonulae occludens The interdigitations are less complicated in superficial zone of lens  permits moulding of lens shape during accomodation

25. Lens Fibre: Structural Arrangements Fetal nucleus  Y shaped of sutures (anteriorly: upright Y; posteriorly: inverted Y) Nucleus formed later i.e. infantile/ adult nucleus  more irregular lens sutures forming complicated dendritic patterns Formation of sutures enables shape of lens to change from spherical to a flattened biconvex sphere Sutural cataract

26. Lens Fibre: Zonal Arrangements Delineate various periods of development of lens Embryonic, fetal and infantile nucleus- constant ; adult nucleus- always increasing Nucleus Central, older, sclerotic fibres Cortex Peripheral, youngest, transparent fibres

27. Lens: Surgical Anatomy

28. Lens: Grading of Nuclear-hardness White/ Green yellow Yellow Amber Brown Black

29. Lens: LOC III classification system Grading based on standardized photographic imaging of opacity

30. Lens: Ciliary Zonules Transparent and stiff nonelastic fibres composed of glycoproteins and mucopolysaccharides Hold lens in position Connect ciliary body to lens thus enable ciliary muscles to act on lens Susceptible to hydrolysis by alpha chymotrypsin  advantage in intracapsular cataract surgery

31. Zonules: Arrangement of Fibres Old concept New concept

32. Physiology & Biochemistry Biochemical Composition Metabolic Activity Permeability & Transport mechanism Transparency Changes with age

33. Lens: Biochemical Composition Water: Major constituent Protein: Major solid constituent Others: Amino acids Carbohydrates Lipids Electrolytes Glutathione Ascorbic Acid 65% 1% 34%

34. Lens: Water Trauma  epithelium breach failure of epithelial pump rapid development of cataract (rosette shaped cataract) Cortex > nucleus Relative dehydrated state: by active Sodium pump [in CM of lens epithelium and each lens fibres] : necessary for lens transparency Traumatic cataract

35. Lens: Proteins Highest 2 Types Clinical Significance Solid Constituent of Lens Relative to any other Organ Crystallin (Soluble Fraction) α , β , & ϒ Albuminoid (Insoluble Fraction) Organ Specific & Not Species specific Individual can get sensitized to one’s own lens proteins. Phacoanaphylaxis is sensitization to lens protein leading to severe inflammation [ phacoantigenic / phacoanaphylactic uveitis] and secondary glaucoma [ phacoanaphylactic glaucoma]

36. Lens: Proteins Albuminoid and alpha crystallin are: Inversely proportional Chemically related Immunologically similar Cortex Young fibres more soluble proteins No albuminoid Nucleus Old fibres more insoluble proteins Entirely albuminoid Ageing: Soluble fraction (alpha crystallins) converted into insoluble fraction (albuminoids)

37. Lens: Proteins 3 types of Crystallin ( Structural protein- Major bulk of refractive fibres) α : largest, max molecular weight, max positive charge β : heterogeneous ϒ : smallest, nucleus, decrease with age Refractive property of lens: d/t increased concentration of crystallin Transparency of lens: d/t short range order of crystallin 2 types of Albuminoid Urea soluble fraction and Urea insoluble fraction

38. Lens: Others- Amino Acid 2 Types Proteogenic Non-proteogenic Except: tryptophan, cysteine, hydroxyproline AA Relatively High In Lens than Aqueous Humour or Vitreous Acidic > Neutral > Basic

39. Lens: Others- Carbohydrate Sorbitol Inositol Ascorbic acid Gluconic acid glucosamine Free Glucose Fructose Galactose Derived

40. Lens: Others- Lipid Lubricating cement substance Clinical Significance In ageing Cholesterol increases and Glycerides decreases In Cataracts Free lipid & Lecithin increases Lipoprotein decreases Cholesterol macroscopically evident

41. Lens: Others- Electrolytes Potassium is Predominant Cation Lens has lowest Calcium (cation) content relative to any other tissue Presence of Sodium (cation) in cortex is higher than nucleus Phosphate is Predominant Anion

42. 7. GLUTATHIONE 3 Amino Acids (1) Glutamic acid (2) Cysteine (3) Glycine Gamma glutamyl cysteinyl glycine Most reactive constituent due to Sulphahydryl group Oxidised (GSSG) Lens: Others- Glutathione Reduced (GSH) 95% 5%

43. Lens is exposed to attack by oxidative agents Enzyme systems are available to minimize/ buffer the effects. eg : catalase, glutathione peroxidase, glutathione-S-transferases, SODs Glutathione is at highest concentration in lens epithelium and detoxification via Mercapturic pathway is an important mechanism In G6PD deficiency, due to failure of glutathione antioxidant mechanism, there occurs oxidative injury to lens and cataract formation. Prevention of experimental cortical cataract by Vitamin E and glutathione also supports this connection Especially the cation transporting membrane proteins Lens: Others- Glutathione Contributes to Redox System Protects thiol groups in proteins

44. Lens: Metabolic Activities- Glucose metabolism Major Source of energy Active transport of ions and AAs Lens dehydration Lens transparency Continuous synthesis of proteins and glutathione Aqueous humour is the main source of glucose Essential For normal lens functioning In absence of glucose, lens rapidly uses up endogenous sources of energy, gains water and loses transparency Cataract occurs in infantile hypoglycemia

45. Lens: Metabolic Activities- Glucose metabolism 4 pathways Anaerobic Glycolysis 80% 2 ATP Krebs Cycle 3% 36 ATP Mostly limited to lens epithelium HMP Shunt 0 ATP NADPH and pentose : nucleotide synthesis, reduced state of glutathione, sorbitol pathway Sorbitol Pathway 5% Sugar cataract

46. Sugar cataract Galactosemic Deficiency of galactose-1-phosphate uridyl transferase Reversible cataract Bilateral Oil droplet cataract Diabetic Seen in juvenile and young diabetics Snowflake cataract/ Snowstorm cataract

47. Lens: Metabolic Activities- Protein metabolism Synthesis Catabolism Amino acids [active transport From aqueous humour] Peptides ATP, RNA Template By proteases and peptidases Lens undergoes autolysis in in-vitro sterile conditions Rate : slowest at nucleus

48. Lens: Transport mechanism Active Passive AA Potassium Taurine Inositol Extrusion of sodium Water Ions Carbon dioxide Lactic acid

49. Lens: Water and electrolyte transport Cation pump Energy dependent & at the Level of anterior epithelium Membrane bound Na-K ATPase  Uptake of K & Extrusion of Na Pump-and-leak mechanism of cation balance Osmometer Na+, K+ act osmotically active compound that drags water with them Exposure of lens to surface active detergent/ antibiotics Disrupts physiochemical integrity of membrane Extrusion of Na via Pump with subsequent gain of Na via leak Dragging of water into lens leading to Swelling of lens & loss of transparency

50. Lens: Other Transport Free Amino Acid Metabolism Protein Leak Leak Epithelial Pump Amino Acid Transport Inositol Transport Glucose Transport Active transport into lens Simple and facilitated diffusion In both anterior and posterior surfaces

51. Lens: Electrical Phenomena -70mV Across Lens Capsule Inside of Lens is electronegative than surrounding -23mV In Lens Fibre -23mV Between anterior and posterior surface

52. Lens: Transparency Opaque at early stage of development due to Tunica vasculosa With development, loss of hyaloid vascular supply Transparent at birth Factors responsible for transparency Single layer of epithelium Semipermeable lens capsule Highly packed lens cells : less extracellular space – small zones of discontinuity Characteristic arrangement of lens fibres Relative dehydration due to pump mechanism Avascularity Auto-oxidation Changes in lens transparency are seen in Cataract

53. Lens: Ageing Age related changes are of 4 types Physical changes Increased weight and thickness Increased light absorbance; decreased light transmission Increased light scattering Fluorescence No change in RI of human lens Metabolic changes Decreased proliferative capacity Decreased enzyme activities Increased urea soluble proteins Decreased glutathione and ascorbate Loss of SOD and G6PD activity Crystallin changes Disappearance of α -crystallins from nucleus Polydisperse β-crystallins Loss of ϒ -crystallins Plasma membrane and cytoskeleton changes Loss of hexagonal cross section and interlocking devices of lens fibres Loss of lipids and proteins including cytoskeletal proteins and membrane polypeptides Increase in sodium and calcium inside cell- decrease in membrane potential Changes in membrane integrity

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