Lens Anatomy and Physiology Flashcards

Lens Anatomy and Physiology

Introduction

• The lens has the ability to change shape, thus altering its power, which allows variable focusing.

• Understanding the anatomy and physiology of the lens is essential for understanding this function.

Lens Location and Gross Anatomy (Slit Lamp Photographs)

• The lens is located behind the pupil.

• The top image shows the anterior pole to the left and the posterior pole to the right.

• Curvature is more pronounced at the back of the lens.

• Top: focused on corneal reflex

• Bottom: focused on posterior pole of the lens

General Anatomy

• The lens is a transparent, avascular, elliptical structure held behind the aperture of the pupil by the suspensory ligaments of the ciliary body.

• It refracts light to a focal point on the retina and changes shape to accommodate viewing objects at varying distances.

Dimensions and Shape

• Transparent and biconvex.

• Average Adult Dimensions:

• Anterior Surface:

  • Flattest, with a radius of curvature (ARofC) of ~10 mm.

• Posterior Surface:

  • More curved, with a radius of curvature (PRofC) of ~6 mm.

• Shape is comparable to a smartie or M&M.

Anatomical Landmarks

• Anterior and posterior poles (apex).

• Lens axis (connects poles).

• Equator (most peripheral part).

Major Lens Components

• Lens capsule (elastic membrane).

• Anterior epithelial layer (forms new lens fibers).

• Lens proper (lens fibers):

  • Cortex (outer layers) (developed after puberty).

  • Nucleus (inner layers) (developed before puberty).

Lens Structures

• Lens Capsule

  • Elastic membrane that envelops the entire lens.

  • Variable thickness (thickest near the equator ~20 µm, thinnest at the posterior pole ~3 µm).

  • Composed of multiple basement membranes (~40 units).

  • Reticular fiber composition (GAGs, glycoproteins, collagen type IV).

  • Lens shagreen.

• Lens Capsule Roles

  • Surrounds the lens & maintains its structural integrity.

  • Gives lens shape, moulds the shape of the lens during accommodation.

  • Chemically tough; restricts penetration of molecules into the lens.

  • Turnover of its constituents, though no evidence for independent metabolism.

• Lens Shagreen

  • With specular microscopy a beaten metal appearance is visible at the interface between aqueous and anterior capsule, termed the lens shagreen.

  • Scanning electron microscopy reveals a pebble-like appearance of the lens capsule which corresponds to the shagreen.

• Lens Epithelium

  • Single layer of cuboidal cells on the anterior surface only.

  • Apices of cells inward.

  • Subpopulations: central, germinative, transitional.

Lens Epithelium Zones

• Central Zone

  • Squamous appearance with elliptical nuclei in section; polygonal with round nuclei in whole mount view.

  • Range of cell diameters, average height ~6 µm, width ~13 µm.

  • Contain organelles typical of epithelial cells.

  • Heavily interdigitated lateral walls.

  • Non-mitotic.

  • Role in transporting substances from aqueous into the lens.

  • Role in secreting capsular material.

• Germinative Zone

  • More peripheral cells.

  • Smaller, more cuboidal.

  • More compact nuclei.

  • More organelles.

  • Interdigitations.

  • Mitotic: daughter cells migrate to the transitional zone.

• Transitional Zone

  • Secondary differentiation.

  • Cells here have increased ribosomes and microtubules.

  • Become more columnar.

  • Assume a pyramidal shape, with the basal portion wider than the apex.

  • Little/no mitosis.

  • Cells differentiating into lens fibers.

Lens Proper (Fibers)

• Make up the bulk of the lens cortex and nucleus.

• Extend to 10 mm in length, hexagonal cross-section.

• Added throughout life, ~5 fibers/day.

• Sutures: Fibers meet anteriorly and posteriorly.

• Progressive internalization of fibers.

• Maturation of fibers: Decrease in the number of cytoplasmic inclusions; nucleus disappears.

Lens Fibre Organisation

• Highly ordered arrangement

• Minimum intercellular space

• Edge processes, ridge joints, tongue-and-groove interdigitations

• Lateral faces, ball-and-socket

• High density gap junctions

• Older fibres, tongue and groove

Formation of New Lens Fibers

• The number of lens fibers increases throughout life as new fibers are continually added, but none are removed.

• The anterior epithelium is the source of new cells for the lens.

• Division occurs in the germinative zone, elongation in the transitional zone, and then new fibers move into the lens cortex.

• During differentiation, fiber cells elongate greatly and express large amounts of proteins.

• The crystallins acquire several specializations of their plasma membranes, and the nucleus moves anteriorly (lens bow).

• All membrane-bound organelles degrade.

Denucleation

• Normal differentiating fibers undergo denucleation and loss of organelles.

• Mature fibers filled with crystallin proteins are clear and have a high refractive index.

• Abnormal development occurs with mutations in the α-, β-, and γ-crystallin families:

  • Retention of nuclei and organelles

  • Formation of vacuoles

  • Abnormal aggregation of crystallin proteins and cataract formation.

Formation of Lens Shells

• The many elongating epithelial cells produced at the equator at the same time become long lens fibers that form new lens shells.

• Each new lens shell has one more fiber than the previous shell.

• Approximately 5 new shells are added each year after the age of five.

• An aged lens has about 3.6 million lens fibers and about 2500 shells.

Lens Sutures

• Anterior and posterior meeting point of lens fibers in the center of the lens.

• Increases in complexity as the lens grows.

• Lens fibers flare in width and curve as the suture is approached.

• Foetal lens: 3-point suture

• Adult lens: 9-point suture.

Why is the Lens Transparent?

• The lens itself lacks nerves, blood vessels, and connective tissue.

• Optical homogeneity.

• Lens fibers packing is dense.

• Fibers have no organelles.

• Paracrystalline protein structure, unusually small soluble ordered proteins (~20-30 kDalton MWt).

• Proteins are soluble, but overall, the lens is dehydrated.

• No large fluctuations in refractive index.

• Proteins >50 kDa MWt diffract light, dilute solutions scatter light; both are avoided.

Maintaining Transparency

• Glutathione (GSH) is a vital lens antioxidant formed by 3 amino acids (glycine, cysteine, and glutamate), which protects the lens from oxidation.

• GSH scavenges reactive molecules, protecting exposed protein thiols from oxidation.

• It is synthesized by the lens epithelium.

• Oxidized glutathione (GSSG) is rapidly reduced to GSH by GSH Reductase (GR) in the presence of NADPH.

• The synthesis and recycling of GSH declines with age, leading to a rise in GSSG.

• The relatively low ratio of GSH to protein-thiol-SH makes the aged nucleus vulnerable to oxidative stress

• Further oxidization forms protein–protein disulphides (PSSPs),

  which are high-molecular-weight, water-insoluble lens proteins that scatter light

Lens Proteins & Aging

• Conversion of soluble to insoluble proteins due to protein aggregation.

• Accumulation of low molecular weight polypeptides in cells due to crystallin degradation.

• Soluble alpha crystalline gradually converted to albuminoid insoluble protein with age.

• The proportion of insoluble protein increases with age.

Lens: A Unique Metabolic Situation

• Located away from blood vessels (no blood vessels or lymphatics or nerves).

• Access to nutrients/waste disposal only via aqueous and vitreous

Why does the Lens Require Energy?

• To maintain lens dehydration & transparency.

• To transport ions and amino acids.

• Synthesis of new proteins and lipids.

• ATP is also required as a phosphate donor (protein synthesis).

• Epithelium has the greatest energy demand.

More Mitochondria in the Lens Epithelium

• Mitochondria are large enough to scatter light.

• Key function is energy production.

• Lens epithelium is most important in lens metabolism.

Main Metabolic Pathways

• Anaerobic:

  • Occurs throughout the lens; no oxygen.

  • 80% of glucose metabolized.

  • 66% ATP generated.

  • 2 ATP/glucose (not very effective).

  • Lactic acid end product into the aqueous.

• Aerobic:

  • Occurs at the epithelium.

  • 3% of glucose use supplies 20% of ATP.

  • 38 ATP/glucose (very effective).

• Sorbitol:

  • 5% glucose metabolized; converts glucose to sorbitol.

  • Prevents the development of diabetic cataracts.

• Hexose Monophosphate Shunt:

  • 15% of glucose is metabolized.

  • Generates pentoses used in nucleic acid synthesis.

Lens Development and Growth

• Lens morphogenesis begins with the thickening of surface ectoderm overlying the optic vesicle, which then invaginates (lens pit).

• It closes over to form the lens vesicle.

• Cells lining the posterior wall elongate (primary lens fibers) to fill the lumen.

• The axial lens thickness in young adults is 3.5 mm and increases to ~5 mm at 65 years (~23 µm/year).

Naming of Cataracts Based on Location

• Congenital Cataracts:

  • Lens opacity present at birth.

  • Ranges in severity: Some do not progress and are visually insignificant; others can produce visual impairment.

  • May be unilateral or bilateral.

  • Classified by morphology, genetic cause, metabolic disorders, and systemic findings.

• Lamellar/Zonular Cataract

  • Due to a problem that occurs when one of the shells are forming.

  • The lamellar subtype (the most common type of congenital cataract) is characterized by an opaque layer surrounded by a relatively clear nucleus and cortex.

  • Lamellar cataracts are typically bilateral but slightly asymmetric and generally have autosomal dominant inheritance.

• Congenital Anterior Polar Cataract

  • Congenital (autosomal dominantly inherited).

  • The majority are very small and located at the anterior pole of the lens.

  • May involve only the capsule, subcapsular area,

    or may be pyramidal and project into the anterior chamber.

  • Most do not need to be removed with surgery and will not harm a child's vision.

• Mittendorf Dot

  • A small, circular opacity on the posterior lens capsule.

  • Represents the anterior attachment of the hyaloid artery.

  • Failure to regress can lead to benign findings, such as a Mittendorf dot or a Bergmeister's papilla, or pathologic changes in persistent foetal vasculature syndrome.

Accommodation

• Accommodation is the process in which the eyes see objects at different distances and maintain clear images of the objects by the convergence and divergence of light.

• The anterior surface decreases in radius and becomes steeper.

• The lens becomes more spherical, increasing thickness and decreasing diameter at the equator.

Amplitude of Accommodation

• Maximum increase in optical power that an eye can achieve in adjusting its focus from far to near.

• Variation of amplitude of accommodation with age.

• Presbyopia is the decrease in accommodative amplitude with age.

Symptoms of Presbyopia

• Inability of the eye to focus up close.

• Part of the ageing process.

• Symptoms include:

  • Difficulty reading.

  • Holding reading material further away.

  • Near objects are blurry.

  • Squinting to see up close.

Why does Presbyopia Occur?

• Decreased elasticity of lens capsule.

• Hardening of lens substance.

• Altered lens dimensions with growth – ↑ diameter, thickness, weight.

• Shift in zonular insertion points (late change).

Post-natal Lens Growth

• 65 mg at birth, 150 mg at 20 years, to >250 mg at 90 years.

• 3.5 mm axial thickness in young adult to ~ 5 mm at 65 years (increase of ~0.023 mm/yr)

Changes in Lens Stiffness

• Adult nucleus is stiffer than the cortex.

• Stiffness in all parts of the lens increases with age.

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Age Changes

• The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the later development of age-related nuclear cataracts.

Cataracts

• Cataract is an opacification of the lens that is caused by disorganization of lens fibers and proteins within the lens fibers.

• Case of accelerated aging, lens opacification

• With age:

  • Reduction in enzymes (reduces metabolism, and efficiency of ion pumps).

  • Reduction in antioxidants (glutathione, ascorbic acid).

• Lens has less K, RNA, ascorbic acid, ATP.

• Has more Ca, Na, water.

• Leads to osmotic stress.

• Chemical modification of lens proteins, particularly insoluble crystallins.

• Accumulation of metabolic products and free radicals.

• Change to membrane.

• Protein aggregations diffract light.

• Changes in water/protein balance scatter light.