Crystalline Lens.pdf

Crystalline Lens Karen Gil MD, MHSN. Lens Development • 27th day development of the lens occurs • While optic vesicles begin to form (before invagination) the adjacent surface ectoderm thickens and forms the lens placode • Lens placode invaginates forming the lens pit, before becoming the lens ves...

Crystalline Lens Karen Gil MD, MHSN. Lens Development • 27th day development of the lens occurs • While optic vesicles begin to form (before invagination) the adjacent surface ectoderm thickens and forms the lens placode • Lens placode invaginates forming the lens pit, before becoming the lens vesicle as it separates form the surface ectoderm Lens Development Lens Development • Lens vesicle is a hollow ball of cells that contains – Anterior lens epithelium – Posterior lens epithelium • Posterior lens epithelium – Differentiates into primary lens cells and elongates anteriorly as fibers, toward the anterior lens epithelium to fill up the lumen – During this process primary lens cells produce crystallins – Primary lens fibers fill lumen forming the embryonic lens nucleus Lens Development • All lens growth after the development of the embryonic nucleus can be attributed to secondary lens fibers • Young lens fibers are very uniform in shape and maintain precise alignment • Only the young outer fibers are nucleated and contain organelles, with age they lose their regularity and become less organized, and their nuclei and organelles disintegrate Lens Development • Anterior lens epithelium – Contains germinative zone, located just anterior to the equator – After the formation of the embryonic nucleus (from the posterior lens epithelium) become columnar an then elongate anteriorly and posteriorly – These fibers end up contributing to the remaining nuclei after embryonic nucleus Lens Development • Anterior lens epithelium becomes secondary lens fibers which form the fetal nucleus • The nuclei in order of growth – – – – Fetal nucleus Juvenile nucleus Adult nucleus Lens cortex • Adult nucleus – Contains fibers form after birth to sexual maturation • Lens cortex – Contains lens fibers formed after sexual maturation • Y inverted sutures seen during slit lamp examination are from secondary fibers, they denote boundaries of the fetal nucleus • Anterior Epithelium – one layer of cuboidal cells • Posterior Epithelium none Crystalline Lens • The lens is a highly organized, transparent structure • Comprises three parts – Capsule • Elastic acellular envelope – Lens epithelium • Single layer of cells which form new fiber cells – Lens fibers • Main mass of the lens • Form the basis of the nucleus and cortex (crystallins) Crystalline Lens • • • • • Avascular Transparent Elliptic structure Focuses light rays on the retina Located – within the posterior chamber – anterior to the vitreous chamber – and posterior to the iris • Suspended from the surrounding ciliary body by zonular fibers • Malleable • Ciliary muscle contraction can cause a change in lens shape increasing the dioptric power accommodation Lens • Posterior lens surface is attached to the anterior vitreous face by the hyaloid capsular ligament – Wieger’s ligament (circular ring adhesion) • Potential space name retrolental space of Berger – area of nonadhesion between the vitreous and lens Lens Dimensions • Biconvex • Anterior radius of curvature – 8-14 μm • Posterior radius of curvature 5 to 8 μm • Poles – center of the anterior and posterior surface • Thickness anterior to posterior surfaces(unaccommodated lens) 3.5-5 mm and increases 0.02 each year through life • Lens diameter (nasal to temporal) – 6.5 mm infant – teenage 9mm and does not change significantly • Equator is the largest circumference of the lens between the two poles Lens Composition • Refractive power 20 D in unaccommodated lens • 1/3 of the lens is protein • 2/3 is water • PH 6.9 • Protein contents varies among the lens with a higher refractive index – in the nucleus (1.50) – less in the outer cortical surface (1.37) • Higher refractive power in the center Lens Capsule • Elastic acellular envelope • Basement membrane • Allows passage of small molecules both into and out of the lens • Provides barrier function preventing large molecules as albumin and hemoglobin enter • Thickness varies upon the regions – Thickest region (anterior and posterior) in the equator: 21 - 23 μm – Thinnest region posterior pole: 4μm – Equator -17 μm – Anterior pole - 9-14 μm Lens Epithelium • Anterior lens epithelium – cuboidal epithelium – Secrete the anterior capsule throughout life – Site of metabolic transport mechanisms – Basal aspect is adjacent to the capsule • Posterior lens epithelium – Absent – Used during embryologic development (form primary lens fibers) Lens • Germinal zone – Preequatorial region (just anterior to the equator) – Cell mitosis – Cell division throughout life – Cells differentiate in lens fibers • as they elongate loose the cellular organelles – The basal aspect stretches toward the posterior pole – Apical aspect toward the anterior pole – Cellular nuclei move with the cytoplasm Lens Fibers • All fibers formed from mitosis in the germinative zone • Once it loses its nucleus, they lose his attachment to the basement membrane • Cross section cut shows mostly hexagonal in shape and arranged in concentric rings • Fibers dimensions cross section 3 by 9 μm • Long crescent shape Lens Fibers • Lens fiber cytoplasm – Contain high concentration of crystallins 90% (water-soluble proteins) • Alpha, beta and gamma – 40% weight of the fiber – Contribute to the gradient refractive index – Concentration varies • Cortex 25% • Nucleus 70% – Cytoskeletal network of microtubules and filaments provide structure (actin protein maintain organization) Lens Fibers • Hexagonal in shape • Lie in layers (like skin of an onion) • Individual fibers are connected to one another by “ball and socket” interdigitations • Initially they are attached to the capsule anteriorly and posteriorly • With time lose it attachment, nuclei and interdigitations and cell membranes and become compacted as insoluble protein in the nucleus Divisions of the Lens • Embryonic Nucleus – Center of the lens – Form by the elongating posterior epithelium of primary lens fibers • Fetal nucleus – Includes embryonic nucleus and fibers surrounding it that are formed before birth Divisions of the Lens • Adult nucleus – Include embryonic and fetal nuclei and fibers formed from birth to sexual maturation • Lens cortex – Contain fibers formed after sexual maturation – Divided into • Superficial zone • Internal zone • Deep zone Lens Sutures • Suture – Junction form by the lens fibers when they reach the poles and they meet with the other fibers in their layer – Anterior and Posterior • Anterior suture • Formed by joining of apical aspects of the fibers • Upright Y shape Lens Sutures • Posterior suture – Joining of the basal aspects of the fibers – Inverted Y shape • As growth continues, fibers get larger, sutures become asymmetric and dissimilar Zonules of Zinn • Group of thread-like fibers that attached the lens to the ciliary body • Also name as suspensory ligament of the lens • Microfibils, formed of extracellular matrix (fibrillin and elastin) Zonules of Zinn • Arise form the basement membrane of the nonpigmented ciliary epithelium in the pars plana • Form two column-like structures on both sides of a ciliary process and end at the lens capsule (preequatorial and postequatorial regions) – Primary (attach to the lens) – Secondary (attach to the primary zonules) Accommodation • Emmetropic eye viewing a distant objet – Ciliary muscle is relax – Diameter of ciliary ring is relatively large – Zonules are stretched • Emmetropic eye viewing a near object – Increase in refractive power of the eye (accommodation) – Ciliary muscle contracted – Zonules are relaxed Accommodation • Change in lens shape by contraction of the ciliary muscle increasing the lens power 1. Lens thickness increases anterior to posterior 2. The lens thins along the equator 3. The anterior lens surface moves forward and thus the anterior chamber becomes shallower 4. There is no change in the position of the posterior pole Accommodation • Stimulus that initiates the accommodative mechanism is retinal blur • Dependent on cone stimulation with little influence by rods Lens Physiology • Primary function of the lens – Refraction of light – Transparency of the lens (minimal light scatter) • Transparency – Absence of blood vessels – Few cellular organelles – Orderly arrangement of fibers – Short distance between components Lens Physiology • Metabolic activity mostly occurs in the anterior epithelium maintaining cell and fiber function • Nutrients are obtained form the surrounding aqueous humor and a small contribution of the vitreous • Anaerobic glycolysis is the source of the energy required for cellular metabolism and cellular replication Lens Metabolism • Obtains glucose from aqueous humor • 70% of ATP production is via anaerobic metabolism • Aerobic glycolysis and Krebs cycle are limited to the epithelium or superficial fibers with mitochondria Lens Metabolism • ATP activity is higher in the epithelial cells and newer fibers of the cortex near the equator and lower near the poles • No activity in the lens nucleus Lens Metabolism • Is constantly pumping out water to create the correct constituents optically • Active Na/K pump, uses ATP to maintain a dehydrated lens Lens Metabolism Pathways • Both aerobic and anaerobic pathways require hexokinase – Converts glucose to glucose 6-phosphate • If hexokinase is not present – glucose convert into sorbitol (via enzyme aldose reductase) • Excess sorbitol – create an osmotic gradient favoring water movement into the lens (swelling, damage, cataract formation) Regulation of Lens Proteins • Glutathione – Primary protector against oxidative damage – Transported into the lens by the aqueous humor or synthetized from lens epithelial cells • Ascorbic acid – Prevent oxidative damage (anti-cataract effect) – Lens 3.5 mmol/liter or higher – AH 1.4 mml/liter – Plasma 0.06 mml/liter Oxidative Stress of the Lens • Free radicals are a normal product of metabolic process • UV light absorption can also produce oxidative changes causing the formation of free radicals • Free radicals disrupt cellular processes and amino acid shape within a protein that causes cellular damage • Gluthatione is a reducing agent that detoxifies free radicals preventing damage • Ascorbic Acid also prevents oxidative damage Age Changes in Lens • Decrease in soluble lens proteins (alpha crystallins) • Decrease in ATP content, K ions, amino-acids and inositol • Decrease in glutathione activity (less detoxification of free radicals – cell damage) • Increase in Ca, Na and H2O (more permeability – disruption of ion balance) • Old nuclear fibers loose organelles – Nuclear sclerotic cataract Clinical Manifestations of Aging • Presbyopia – Loss in accommodative ability – Inability to focus at near distances – Changes in ciliary body, zonules, lens capsule and lens itself all influence Clinical Manifestations of Aging • Cataract – Any lens opacity – Greatest cause of blindness – Multiple factors influence lens metabolism to cataract development – Risk factors: • • • • • • • • Aging Diseases Genetics Nutritional Metabolic deficiencies Trauma Congenital Environmental stress Cataract • Types are named according to the location • Graded by the severity • Numerous mechanisms are presumed causative – – – – Fluid and ion imbalance Oxidative damage Protein modification Metabolic disruption Cataract Cataract • Nuclear cataract – Embryonic fetal or adult nucleus – Center opacification – fibers are susceptible to oxidative damage because of the decline of glutathione – Brunescence cataract – yellow coloration Cataract • Cortical cataract – Cortex – Spike-like shape – Thicker in the periphery, follows the shape of the fiber – Progress slowly Cataract • Posterior subcapsular cataract – Located just beneath the posterior capsule – Impacts vision early – Epithelial cells migrate form the equatorial region – Risk factor • Long term use of high dose of steroids • Radiation therapy for cancer Clear Lens Cataract Phacoemulsification https://www.jnjvisioncare.co.uk/slit-lamp-techniques/opticalsection-of-crystalline-lens