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The histology and biology of the lens

Why does cataract occur? Why does the crystalline lens loose transparency? What biological processes are at work? How can cataract be prevented?
To debate these questions and those that follow in this series, we need first to have an understanding of many aspects of the living lens - its structure, shape, physiology, biochemistry, life cycle and how it changes with normal ageing. The many unusual aspects of lens biology have interested diverse researchers from biochemists (studying crystalline chemistry and evolution, membrane chemistry and ageing etc.) to histologists, physicists to physiologists, clinicians to geneticists as well as all sorts of ocular specialists. This article will attempt to bring together information from some of these diverse fields of study. The lens is an unusual tissue. Like everything else in the body there is an astonishing level of cellular interaction, but there is also much that is unique to the lens. It is derived from only one type of tissue, the epithelial cells of surface ectodermal origin with which it starts embryonic life. Lens fibres are offspring of these epithelial cells. There is no replacement (or programmed death) of lens fibres, only continued growth in their population. Despite this lack of cell turnover, the lens remains clear for many decades. The lens has no blood or nerve supply, or any cellular contact with other tissues. Protein concentrations in the lens are very high (about 33%) yet the colloidal osmotic pressure (ability to draw water in) is somehow opposed and the proteins resist their natural urge to stick together, denature and opacify. curious that this flattened shape is shared with other species who share a similar accommodative facility, whilst species unable to accommodate have more spherical lenses. The crystalline lens is suspended radially from the ciliary body by the zonular fibres attached on either side of its equator. The ciliary body encircles the lens and is roughly triangular in cross section. It forms a separated ring roughly concentric with the lens, being attached anteriorly at the scleral spur, and posteriorly at the Ora Serrata. When the muscle within this ciliary body contracts, the body swells radially and reduces the ciliary annulus which via the zonules, allows the elastic lens to take up its preferred accommodated (and more spherical) state. Tension is returned to the lens zonule system by relaxation of the ciliary muscle, causing the lens to flatten ready for distance focusing. The lens has a higher refractive index than the aqueous and vitreous. The lens capsule encases the cellular elements of the lens (Figures 1 and 2). This capsule is a highly elastic thickened basement membrane secreted by the lens epithelial cells. The bulk of the lens consists of lens fibres. These are actually vastly elongated lens epithelial cells that have lost their nuclei and many of their organelles. Since they are no longer cells and are of great length they are called lens fibres. Between the capsule and the outermost layer of lens fibres is a single layer of epithelial cells. These true lens cells continue the task of dividing, to create new lens fibres. The oldest or primary lens fibres remain in the centre of the lens and form the embryonic nucleus of the lens. Subsequent populations of lens fibres are formed in layers like an onion around the primary fibres. The newest lens fibres are found in the outermost layer of fibres in the superficial cortex and are continually formed by the epithelium, so that the lens increases in size and weight throughout life. Lens fibres appear to be tightly joined by a network of junctional structures and membrane modifications with little intracellular space.

ABDO has awarded this article 2 CET credits (GD).

The College of Optometrists has awarded this article 2 CET credits. There are 12 MCQs with a pass mark of 60%.

Figure 1 Diagram of the crystalline lens section

Figures 1 & 2 by kind permission of the Optician

Introduction to the lens

The lens is an optically dense, flexible living lens, located between the primary fixed refracting surface of the cornea and the retina. In common with the cornea, the lens has two principal optical properties - transparency and refractive power. The shape of the human lens can in part be studied using the slit lamp microscope. It is usually described as bi-convex, with anterior and posterior surfaces that approximate to parabolas. Equatorial diameter is about 10mm, and sagital thickness (thickness along the visual axis) between 3.5 and 5 mm depending on age and accommodative state. Compared to the anterior surface the posterior surface is the most steeply curved both unaccommodated and maximally accommodated. The lens increases in sagital thickness throughout life and both surfaces (in the unaccommodated state) steepen after early childhood. It is

Embryonic development of the lens

Cells that are destined to become the lens arise from the same surface ectoderm of the head of the very early embryo that forms the epithelium of the cornea conjunctiva and eyelids. This part of the surface ectoderm is Figure 2 A three dimensional diagram of the lens cut open to reveal the layers of lens fibres

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Zonular fibres close to the capsule Capsule Epithelium (transition zone) Lens fibres

Histology of the lens cells under the microscope

A brief review of the usual features of epithelial cells may be helpful, so that the uniqueness of the lens cells and fibres can be appreciated. There are four basic types of cells found in the body, epithelium, muscle, connective and nerve tissue. Epithelium is usually found in sheets, lining the external surfaces and internal surfaces of the digestive, urogenital, respiratory and cardiovascular systems. Epithelial cells sit on a basal lamina, and there is good adhesion between cells. Typically tight junctions occur at the apical end (away from the basal lamina) of the cell joining adjacent cells and preventing any extracellular transport across the sheet. Gap junctions typically occur between lateral cell faces. Lateral interfaces frequently show interlocking cell membranes which is thought to assist cell to cell adhesion. Cells are made of proteins, carbohydrates, lipid, nucleic acids (DNA, RNA), inorganic materials and water. The cell is enclosed by a cell membrane usually called the plasma membrane, which separate the cell from its environment. Inside is the cytoplasm containing the organelles and the nucleus. The cell nucleus holds the genetic instructions in the form of the DNA and acts as the brain of the cell. It is contained within a nuclear envelope, composed of a double membrane containing pores through which information can pass to and from the cytoplasm. Cytoplasmic organelles are specialised structures within the cell to perform its specific functions and will vary slightly in differing cell types. The endoplasmic reticulum is involved with protein, lipid or hormone secretion. The Golgi apparatus is seen in secretary cells and is involved in the concentration and packaging of secretions. Mitochondria produce ATP for energy and are most numerous in cells that consume the most energy. The cytoskeleton provides structural stability within the cell, maintaining or allowing cell shape change. It is composed of filaments of various sizes and functions.

Figure 3 Light micrograph of superficial human lens, close to the anterior equator showing the lens capsule, epithelium and layers of cortical lens fibres Elongation of developing lens fibres

Lens cells Capsule

Basal ends move under the capsule

Figure 4 Light micrograph of the equator to show developing lens fibres associated with an out pocket (of neural ectoderm) of the developing forebrain, destined to become the optic vesicle by 22 days gestation. The layer of ectoderm thickens and by 28 days the presumptive lens called the lens plate has formed. A few days later this has transformed to the lens vesicle, a hollow single ball of cells. By 44 days, elongating cells from the posterior vesicle have become the primary lens fibres and filled the vesicle. Capsular secretion has also begun. At about 50 days, secondary fibres start to develop from anterior epithelial cells. These secondary fibres are of the same length and meet at a Y shaped suture on either side. The lens shape changes as development continues and becomes more ellipsoidal. Recent interest has fallen on the mechanism and genes involved in inducing the developmental changes from ectoderm through lens plate and lens and from optic vesicle to retina. Chemical signals induce the lens to form from one part of ectoderm whilst others presumably prevent adjacent areas from also turning into lens cells. Various fibroblast growth factors (FGF) have been shown to be responsible for inducing first primary and secondary lens fibre development, influencing elongation and the reduction of organelles, nuclear destruction, development of gap junctions and crystalline synthesis. In addition, a gene known as Pax 6 has been shown to be important in eye development.

Plasma membranes
An understanding of the plasma membrane is important to lens and cataract research. Plasma membranes act as a selective barrier to the passage of molecules, recognise chemical signals from other cells, provide attachment to adjacent cells and provide internal attachment to the cytoskeleton. The plasma membrane consists of a double layer of phospholipid molecules. Whilst the phospholipids provide flexible strength (behaving a bit like a fluid), cholesterol (part of the lipid membrane) is thought to have a role in maintaining the fluidity of the membrane. Proteins built into the membrane structure are called intrinsic (or intrigal), whilst those that can be separated from it (in the laboratory) are called extrinsic,

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and are located towards the outer or inner surface of the bilayer. Membrane proteins are classified according to their molecular size and are given names such as MP26, MP22 and MP70 (M= membrane, P= polypeptide) or MIP... if a major intrinsic protein (MIP) is located. The lipids provide the barrier function whilst the protein molecules act as controlled channels to allow selective substances through. Membrane modifications occur at cell junctions. Desmosomes are consistent with cell adhesion, tight junctions (also called zonular occludens) with sealing off extracellulaer space, and gap junctions with electrical and metabolic communication. Gap junctions are unusual in that they consist of interconnecting channels formed from protein strands (called connexins) which join up to form channels called connexions. Connexions are a little like small pores or tunnels between cells and effectively connect one cytoplasm to another for the passage of small molecules only. The plasma membrane is not a total barrier. Small non-ionised molecules can cross the membrane by diffusion or dissolving into the lipid layer. Charged molecules and ions have rather more trouble, and intrinsic proteins are organised into specific channels to allow their passage. Different channels exist to allow specific (or specific combinations of) ions to diffuse through. Common protein channels are Na+, Cl- K+ Ca++. Mediated channels and ion pumps also exist to assist desirable molecules in (or undesirable ones out) that cannot use diffusion. Carrier proteins in the membrane, containing a specific site bind to the molecule and release it on the other side.

of new lamellae, either on the inside of new lamellae, or added at the inner surface and pushed through towards the outer surface.

Figure 5 Sutures of the lens

The epithelium
The lens epithelium is derived from the original cells of the lens vesicle. In the mature lens, it forms a monolayer beneath the anterior and equatorial capsule. Except at the equator, where differentiation and elongation occur, cells appear cuboidal in section, and roughly hexagonal in flat mount (the orangepeel effect seen with the slit lamp). Neighbouring cells have interdigitations (Figure 6c) with each other associated with junctional specialisations (desmosomes and gap junctions) which not only hold the cells tightly together but also allow excellent communication between cells. These lateral interdigitated membranes are involved also in enzyme production and with the active pumps such as the sodium ion pump. Epithelial cells have many roles in addition to lens fibre production. Synthesis of crystallins and membrane proteins, transport through active pumps of ions and water, and secretion of capsular precursors, are just a few of their duties and they are rich in cytoplasmic organelles. Junctional specialisations are important not only for mechanical stability (important in a flexible tissue which must remain transparent) but for control of both ion transport between cells which have no nerve supply and transport of metabolites between cells which have no blood supply.

Figure 5a Sutures at the centre of a human lens

Courtesy of G.L. Ruskell

Figure 5b Surface suture at the periphery of a human lens

Courtesy of G.L. Ruskell

Formation of lens fibres

(Figure 4) Epithelial cells divide, pre-equatorially, the new cells moving outwards, towards the posterior equator, where they elongate and differentiate into lens fibres. The apical (away from capsule) end of the cell pushes forwards, under the epithelium and over the next youngest layer of cortical lens fibres, to terminate eventually forming an anterior suture, whilst the basal (next to capsule) process moves backwards, beneath the posterior capsule until they meet at posterior sutures. As they elongate, cytoplasmic organelles decrease and with the exception of occasional mitochondria, disappear. The nucleus breaks down about the same time as the basal end terminates (at a posterior suture). Interdigitation increases and at the sutural ends bispheroid terminal bodies (of unknown significance) form from aggregations of ribosomes. Desmosomes become rarer and disappear, but gap junctions proliferate as the membrane enlarges covering between 5 and 60% of the membrane surface. These gap junctions are of a type unique to lens fibres and are different to those found in the epithelium.

The lens capsule

The lens capsule encases the lens (Figure 1). It is a highly elastic, replicated basal lamina, formed from the basement membrane of the epithelium. Using electron microscopy, the capsule reveals a laminar structure (Figure 6b), whilst with the slit lamp it appears structureless. Each lamina consists of sheets of tiny parallel collagen filaments. The capsules elasticity may be due to a superhelical arrangement of filament strands. There is a denser outer layer, which is believed to contain a mixture of capsular collagen filaments and zonular elastic microfibrils. Zonular fibrils run tangentially to the lens surface at their attachment into the capsule. Most penetrate only a short distance into the capsule, but some bundles of these fibrils are found as deep as the epithelial surface. The human lens capsule is a fairly even thickness at birth, about 4m around the anterior and equatorial lens, thinning slightly at the posterior pole to 3.5m. As the lens volume increases, the capsule has to grow to maintain its thickness but it also continually thickens anteriorly and equatorially. The capsule increases in thickness, by deposition

Figure 5c Cortical suture seen with scanning electron microscopy (SEM) (monkey). Note how lens fibres broaden as they approach the suture line.

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Lens fibres
The great bulk of the lens is composed of lens fibres (Figure 2). The lens nucleus contains the original embryonic (primary) lens fibres, surrounded by the fibres (secondary) of the foetal nucleus, which join at the Y sutures, and then in turn the postnatal lens fibres of the infant and adult nucleus. These latter and those of the cortex, terminate at more complex branching sutures (Figure 5). Cortical fibres are very thin, roughly hexagonal in cross section, and very long. They are slightly spindle-shaped, being wider and thicker as they cross the equator. In deeper cortical layers, the membranes can be so heavily interdigitated and the fibres so thin, that the six-sided nature of the fibres is not at all clear (Figure 7c). Nuclear fibres although a little narrower, tend to be thicker. Lens fibres from the cortex of the young human, are approximately 7-10mm in length, very thin, roughly hexagonal in section, and appear tightly joined by complex interconnections. Specialised gap junctions are abundant and often associated with processes. It is thought that the gap junctions allow metabolic communication throughout the avascular lens, and these seem to be adapted to their unusual environment. Electrical coupling of lens fibres by gap junctions, has however, still to be demonstrated in primates. Gap junctions in lens fibres are different to those found elsewhere in epithelia. They are larger with less tightly packed particles (connexions), and the gap between adjacent membranes is smaller than in other tissues. The actual protein combinations of the connexions are unique to the lens. Using scanning electron microscopy (SEM) (Figures 6, 7, and 8), three types of fibre surface structures have been identified. The first type is the interlocking processes along the six edges of the lens fibre, which appear to join adjacent fibres. The edge processes appear similar to a zip made up of three rows of teeth. These interdigitating edge processes are more common in the areas of greatest shape change, - the equator and periaxial zones, so it is possible that they may have a role in accommodation. They are also more marked in the deeper cortical zones and the nucleus. A second type of junctional structure occurs on the lateral faces of lens fibres and is usually referred to as the ball and socket junction (Figures 7a and b). These only connect two lens fibre faces, (whereas the edge processes interconnect three fibres) and are most profuse in the cortex, para equatorially, where perhaps zonular forces are most evident. Gap junctions have been observed in association with ball and sockets. In the deep cortex and nucleus, all six surfaces can display folds, sometimes called tongue and groove junctions, or microplique (Figure 8). Their function is unclear, but it has been suggested that they may aid in reducing lateral sliding between lens fibres during lenticular shape changes. Another study described the areas of furrowed membrane as microvilli laying flat on their sides, and reattached apically, suggesting that the deepening tongue and groove pattern in the oldest fibres are a consequence of age (lenticular wrinkles!), and perhaps have no role in accommodative shape changes.

Figure 6 SEM of the superficial lens just posterior to the equator

Figure 6b SEM of the outer lens capsule surface (High Power)

Figure 6a Low power SEM of a lens portion Note how smooth the newest lens fibre appear.

Figure 6d SEM newest lens fibres

Figure 6c SEM of epithelial cells. Note the interdigitated lateral cell walls

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Inside lens fibres

All mammalian non-muscle cells have a cytoskeleton, the part of the cell that, as its name suggests, provides internal support and structure for the cell. Lens fibres also have a cytoskeleton, made up of various cytoplasmic filaments. These filaments make up a network that is anchored to the plasma membrane. Microfilaments in lens fibres are thought to be mostly actin filaments. In other tissues, actin is thought to facilitate cell shape change and assist in cell-to-cell contact. Microtubules increase in number as the new lens fibres elongate, and orientate along the axis of the fibre. They have been found in lens cells and cortical fibres but not in the nucleus. It has been suggested that microtubules give the lens fibres their visco-elastic properties (Maisel et al 1981). Intermediate filaments are usually structural, but in the lens there are also some unique beaded filaments. The beaded filament is in some way essential to transparency (Quinlan 1999) perhaps because it provides attachment sites for crystallins. The cytoskeleton and cell membranes of the lens fibres interact in some way with the lens crystallins, perhaps to control their distribution (essential to transparency) and orientation.

Figure 7a SEM of superficial cortical fibres. Note the numerous ball processes (light) and their sockets (dark)

Figure 7b High power SEM showing fractured superficial lens fibres. Some sockets have broken open in the fracture

The zonular fibres

(Suspensory Ligament, Zonule of Zinn)

The zonular fibres connect the lens to the ciliary body and transmit the force from the ciliary muscle (within the ciliary body) to the lens. These very fine elastic-like fibrillin fibres arise from the pars plana and ciliary valleys (of the pars plicata) of the ciliary body. The fibres are anchored in the pars plicata and attach to the lens in three main zones on the lens, anterior, at and posterior to the equator. It is generally agreed that the zonule allows the lens to take up its accommodated shape when its fibres reduce tension, and impose a flattening on the anterior and posterior lens face when the ciliary muscle relaxes.

Figure 7c Light micrograph of cortical lens fibres (monkey). The many interdigitating processes are so profuse that the six-sided nature of the lens fibres is hard to identify. Edge processes Tongue and groove pattern

Biology of the lens

The main functions of the lens are to transmit and focus light on the retina. The optical properties required to do this are transparency and refraction (high refractive index and curvature). Accommodating lenses also need controlled flexibility, elasticity and the ability to maintain all their required properties during repeated shape changes. The physiological and biochemical processes of the lens must encompass maintenance of those optical properties, which allow it to focus images on the retina. Like all cellular structures the lens needs energy, metabolites, ions, and biochemical communication to remain functional. Its isolation and lack of blood supply, suggest an unconventional physiology. Without a blood supply, the lens must get all it needs (including a waste disposal service) from either the aqueous or the vitreous. The

Note: Tongue and groove pattern on upper and lower fibres faces seem similar

Figure 8 SEM of the nuclear lens fibres (monkey)

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flowing aqueous seems the more likely candidate to supply the majority of these requirements and it is no surprise to find that most the active pumping mechanisms are located in the epithelium, which being on the anterior surface is closest to the aqueous. There is evidence that communication with other tissues is achieved via biochemical messages (such as growth factors FGF to co-ordinate development) carried via the vitreous or the aqueous. The necessity for transparency demands tight limitation on space between cells and fibres. The high protein concentration of the lens should result in a colloidal osmotic pressure to draw in water, which would be disastrous to transparency. There is actually a protein gradient, with the highest concentration of protein found in the nucleus and lowest superficially. Water needs to be kept out and metabolites transported in. Since there is very little extracellular space, transport deep within the lens of ions and metabolites via the extracellular clefts is restricted. Although epithelial cells (and the most superficial lens fibres) have average permeability to passive transport of ions, lens fibre membranes are of a more non-leaky permeability. Specialised gap junctions occur extensively throughout the lens and provide cell to cell (and fibre to fibre) communication. The lens epithelium (with little passive ion transport in the fibres to fight against) is therefore able to control ion transport throughout the lens. Most processes requiring energy or metabolites are situated close to the surface. The sodium pump (referred to earlier) is really a N+ K+ ATPase pump is a mechanism by which sodium levels are kept low and potassium high. This pump is located in the apical and apicolateral regions of the epithelium and in the anterior superficial lens fibres. There is also a Ca+ ATPase pump to keep calcium ions low. Opacity occurs in experimental lenses when calcium or sodium levels elevate, and raised sodium and calcium levels are found in naturally occurring cataract. the lens by facilitated transport mechanisms controlled primarily by the lens cells. Glycolysis is the main source of energy to fuel active mechanisms, cell division and growth. Glucose is broken down to produce ATP (and other high-energy phosphate compounds) which are the power units of the cell. The only available oxygen is in the aqueous and vitreous which surround the lens, both of which have only a low oxygen content. Therefore, production of ATP must be able to occur anaerobically and roughly 70% is produced this way. Some aerobic glycolysis has been shown to occur in the epithelial cells closest to the aqueous that carries the major part of what little oxygen is available to the lens. Production of ATP in the presence of oxygen is very much more efficient than anaerobic glycolysis; so although very little aerobic glycolysis occurs the energy produced from this cycle is not insignificant. Energy production in the lens is a carefully balanced affair. The three enzymes (called kinases) that control anaerobic glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) are all tightly co-ordinated based on the need of the lens for ATP. Other metabolic pathways such as the citric acid cycle, the hexose monophosphate shunt, glycogenolysis and the sorbital pathway are also present in the lens, all delicately controlled and interacting with each other. Details of the biochemistry of metabolism may be found in Harding (1991 and 1997). proteins throughout the cytoplasm so that there are no large fluctuations in refractive index. Benedek (1971) accounted for the transparency of the normal lens fibre cytoplasm by suggesting that there is an absence of scattering units. The lens proteins within the cytoplasm may be too small relative to the wavelength of light to cause scatter or that spacing between the proteins (scattering units) is such that destructive interference occurs. So transparency is due to the optical homogeneity of the lens fibres, which is dependent on the tightly ordered packing of unusually small soluble proteins the crystallins. The cytoskeleton may have the important role of maintaining the even distribution and close packing of the crystallins. The lens membranes and the cytoskeleton consist of insoluble proteins and lipids and have a higher refractive index than the fibre cytoplasm. Recent evidence points to a protein gradient within the lens, and hence a refractive index gradient within the lens.

Crystallins
Lens proteins - the lens crystallins, are rather special. They are produced within the lens during the formation of lens fibres and have exceptional longevity. The higher the proportion of soluble crystallins to water in the lens fibre cytoplasm, the higher the refractive index. The percentage of soluble protein is important to transparency, too much or too little water and the cytoplasm becomes turbid. Although the exact structure of the crystallins are not fully sequenced yet, they all have a tight spherical shape. Crystallins have traditionally been referred to as structural proteins because they were not known to have enzymatic or other specific actions. Lens crystallins were thought to be lens specific, but in the last decade or so, it has been revealed that some are closely related to other body proteins (such as enzymes) having quite different functions. There are three main classes of crystallins , and crystalline. -crystalline is the most abundant crystalline, -crystalline has the highest molecular weight and -crystalline is the smallest both in size and concentration. and -crystalline share their evolutionary history and are related. -crystalline has chaperone like qualities which is a term applied to proteins, which protect other protein molecules from unwanted damage, denaturing, or aggregation. As lens proteins are synthesised during lens fibre development, and retained (i.e. not replaced or broken down for recycling as happens in other body cells), lens fibres can be as old as the organism to which they belong. Having a chaperone-like protein within the lens to keep the longserving proteins in shape or mop up the untidy seems a wonderful solution! Despite the useful properties of crystalline, there is a tendency for the lens

Transparency
The transparency of the lens is due to its optical homogeneity. In common with all the transparent parts of the eye the lens is avascular. The lens is essentially cellular and cells are not usually transparent to light due to absorption and scatter. Light is scattered by most of the constituents of a normal cell including the cell walls, the cytoskeleton and organelles within the cytoplasm. Many molecules absorb light but the lens needs to transmit those wavelengths required by the retina, whilst being opaque to those that may otherwise harm it. The young human lens transmits light with wavelengths between 450 and 1200 nm. The physical basis of lens transparency is not fully understood. Lens fibres are arranged in layers, each layer approximately perpendicular to the light entering the eye and there is little extracellular space to disrupt the regular array. Thus light scatter due to the plasma membranes, although still present is minimised. Lens fibres have very few organelles to scatter or absorb light and those that remain in immature lens fibres are confined to the equatorial regions, shaded by the iris. There is very little light scatter from cytoplasm of normal lens fibres and their proteins are soluble. It has been suggested (Trokel 1962) that the transparency is a consequence of an even distribution of lens

Lens metabolism
The lens is metabolically rather less active than most other tissues. Energy is required for all active processes essential to growth and maintenance of transparency such as cell division (including manufacture of new proteins and lipids and other necessary constituents of new lens fibres) transport of metabolites and waste products, and the sodium/potassium ion pump. The epithelial cells are the most metabolically active part of the lens whilst the most superficial developing lens fibres are less active and the deeper lens fibres of the deep cortex and nucleus relatively inactive. Transport of metabolites such as ions, glucose, amino acids and lipid precursors (required for maintenance and production of new lens fibres), occurs from the aqueous to

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proteins to change with age. Proteins tend to increase in average molecular weight, and loose their compact curled up shape. This results in larger proteins (which are less soluble) causing light to scatter. Having discussed the histology and biology of the lens, age related changes and an account of the biology of cataractogenesis will be discussed in following articles.

References and further reading

1. Benedek, GB (1971). Theory of the transparency of the eye. Appl Optics, 10: 459-473. 2. Burd HG, Judge SJ and Flavell MJ (1999) Mechanics of accommodation in the human eye Vis.Res. 39 (9) 15911595 3. Bloemendal (Ed) (1981)Molecular and cellular Biology of the Eye Lens. Pub: Wiley 4. Brown NAP (1973) The Change in Shape of the Internal Form of the Lens of the Eye on Accommodation Exp. Eye Res. 15, 441 5. Brown NA Phelps and Bron AJ (1996) Lens Disorders. A Clinical Manual of Cataract Diagnosis Pub: Butterworth-Heinemann 6. Clarke J I, Matsushima H David LL and Clark JM (1999) Lens cytoskeleton and transparency Eye 13 (3b) 417424

7. Dahm R van-Marle J Presscot AR and Quinlan RA (1999) Gap junctions containing alpha8-connexin (MP70) in the adult mammalian lens epithelium suggests a re-evaluation of its role in the lens Exp.Eye.Res. 69(1) 4556 8. Fisher RF (1969) Elastic constants of the human lens capsule and The Significance of the shape of the lens and capsular energy changes in accommodation J.Physiol. 201: 1-47 9. Fisher RF (1971) The Elastic Constants of the Human Lens J.Physiol 212: 147-180 10. Glassser A and Kaufman PL (1999) The mechanism of accommodation in Primates Ophthalmology 106 (5) 863872 11. Harding JJ (1991) Cataract, Biochemistry, Epidemiology and Pharmacology Pub Chapman and Hall 12. Harding JJ (1997) Lens in Biochemistry of the Eye Pub Chapman and Hall 13. Hart WMH (Ed) (1992) (9th Edition) Adlers Physiology of the Eye Chapter 10 The Lens and Chapter 11 Accommodation and Presbyopia Pub: Mosby 14. Koretz and Handelman (1988) How the Human Eye Focuses Scientific American July 65-71 15. Krag S (1995) Age related changes in the

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mechanical properties of the anterior lens capsule (Poster) Vis Res 35 Sup 222 Kuszak and Novak (1994) The Ultrastructure of the Epithelial Fibre Interface In Crystalline Lenses Investigative Ophthalmology and Visual Science, Vol 35 No4 pg 1639 Ludwig K, Wegscheider E. Hoops JP and Kampik A (1999) InVivo imaging of the human zonular apparatus with high resolution ultrasound biomiscroscopy Graefes Arch. Clin Exp Ophthalmol. 237 (5) 361-371 Maisel (Ed) (1985) The Ocular Lens, Structure, Function and Pathology Pub: Marcel Dekker, New York. McAvoy JW, Chamberlain CG, de Iongh RU, Hales AM ,Lovicu FJ, (1999) Lens Development Eye 13, 425437 Sterling and Griffiths (1991) Scanning EM studies of Normal Human Lens Fibres and Fibres from Nuclear Cataracts Eye, 5: 86-92. Trokel, S (1962) The physical basis for the transparency of the crystalline lens. Invest Ophthalmol, 1: 493-501. Wistow G (1995) Molecular Biology and Evolution of Crystallins: Gene Recruitment and Multifunctional Proteins in the Eye Lens R.G. Landes Company Pub: Springer

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Multiple choice questions - Please note there is only ONE correct answer The histology and biology of the lens
1. Which one of the following statements is incorrect? Lens fibres: a. develop from lens epithelial cells b. derive from surface ectoderm in the embryo c. make up the bulk of the adult lens d. are roughly octagonal in cross section 2. Which one of the following statements is incorrect? The adult human crystalline lens: a. increases in weight with age b. in its unaccommodated state flattens with age c. has a higher refractive index than the aqueous and vitreous d. is flattened by increasing zonular tension 3. Which one of the following statements is incorrect regarding plasma membranes? a. the plasma membrane is a barrier to all ions b. gap junctions are found between lens fibres and between epithelial cells c. plasma membranes consist of phospholipids and proteins d. membrane proteins are classified according to their size 4. Transparency of the lens is thought to be due to: a. pigments in lens fibres b. increases small particle light scatter c. absence of cytoskeleton in the fibres d. optical homogeneity 5. Which one of the following statements regarding lens proteins is incorrect? a. the proportion of soluble crystallin to water is important to transparency b. -crystallin is the most abundant protein in the lens c. -crystallin has chaperone like qualities d. crystallins are produced during the formation of lens fibres 6. Lens fibres differ both structurally and functionally in differing lens localities. Which one of the following statements is incorrect? a. deep lens fibres are thought to have a less leaky permeability than superficial lens fibres. b. primary lens fibres retain their nuclei throughout their life c. in scanning electron microscopy (SEM) lens fibres of the deep cortex and nucleus show folds called tongue and grooves d. basal ends of developing lens fibre proceed posteriorly just beneath the capsule, meeting at a posterior suture. 9. Which one of the following statements regarding the postnatal lens is incorrect? a. there is no programmed cell death or replacement of lens fibres within the lens nucleus b. a Ca+ ATPase pump keeps calcium ions low c. the lens is metabolically less active than most other tissues d. the aqueous is the only medium for communication with other organs 10. Which one of the following statements is correct regarding lens development within the first month of embryonic life? a. primary lens fibres join form the Y suture b. secondary lens fibres of the embryonic nucleus join at the Y sutures c. secondary lens fibres of the infant nucleus join at the Y sutures d. lens fibres of the cortex join at the Y sutures 11. Which one of the following statements regarding the lens capsule is incorrect? a. the lens capsule is formed by the epithelium b. the capsule encases the cellular elements of the lens c. capsular production begins after birth d. the lens capsule is a highly elastic basal lamina 12 Which one of the following statements regarding gap junctions is incorrect? a. gap junctions are important to lens physiology b. channels from adjacent gap junction align to form connecting channels called connexions c. gap junctions in the epithelium, superficial and deep lens fibres are of all exactly the same variety d. gap junctions are usually involved with electrical and metabolic communication.

7. Which one of the following statements regarding lens metabolism is correct? a. anaerobic glycolysis is the main source of energy for the lens. b. elasticity of the lens is dependent on the citric acid cycle. c. 50% of ATP production in lens fibres is achieved by aerobic glycolysis. d. hexokinase is a structural protein important to ion channels.

8. Which one of the following statements regarding the human lens curvature is correct? a. the posterior surface is only the steepest during maximal accommodation b. the anterior surface of the lens is always more steeply curved than the posterior c. the posterior lens surface is always the more steeply curved d. the anterior surface is the steepest during maximal accommodation whilst the posterior surface is the steepest in the unaccommodated state.

An answer return form is included in this issue. It should be completed and returned to: CPD Initiatives (c2983a), OT, Victoria House, 178180 Fleet Road, Fleet, Hampshire, GU13 8DA by February 7, 2001.

ABOUT THE AUTHOR

Margaret Stafford is an optometrist who works in the contact lens department of Moorfields Eye Hospital and in independent practice. An examiner for the College of Optometrists, she teaches first year anatomy and physiology at City University and also helps in its Childrens Optometry Clinic.

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