THE LENS

Question 1

Which 3 of the following statements best describe the location of the lens?

Answer 1

Anterior to the vitreous
Posterior to the cornea
Posterior to the iris

Question 2

Which of the following structures/cells elongate(s) to become the primary lens fibers?

Answer 2

Posterior lens epithelium

Question 3

At which of the following locations is the lens capsule the thinnest?

Answer 3

Posterior pole

Question 4

Which region of the lens capsule is removed (capsulorhexis) to gain access to the lens during cataract surgery?

Answer 4

Anterior capsule

Question 5

Which of the following lens zones is the location where cells differentiate into new lens fibers?

Answer 5

Transitional zone

Question 6

Which of the following lens areas is directly anterior to the posterior lens capsule?

Answer 6

Cortex

Question 7

Consider the image. Which of the following areas of the lens is being highlighted by the red arrow?

Answer 7

Embryonic nucleus

Question 8

Zonules originate from which of the following locations?

Answer 8

Basement membrane of the non-pigmented epithelial cells of the pars plana

Question 9

Consider the image. Which of the following lens anomalies is best displayed in the image?

Answer 9

Posterior subcapsular cataract

Question 10

Compare the curvature of anterior vs. posterior surface of the lens. Which is steeper?

Answer 10

The lens is roughly shaped like a soup bowl placed upside down on a dish. The anterior surface is relatively flat (dish) with a large radius of curvature. The posterior surface is steeper and more convex.

*lens equator = widest circumference of lens (where edges of dish and soup bowl meet)

Question 11

Describe lens development in terms of:

• what does the lens capsule of the lens vesicle develop from? Why?
• in the adult lens, why is the posterior capsule at the posterior pole so thin?
• where does the adult anterior epithelium develop from?
• why doesn’t the adult lens have a posterior epithelium?
• what do the posterior lens epithelial cells of the lens vesicle become in the adult lens?

Answer 11

SKIP TILL LATER

Question 12

What is the lens capsule? Why does it appear bumpy?

Answer 12

It is the basement membrane of the lens
epithelium (initially formed by the anterior and posterior lens epithelial cells during development) and completely surrounds the lens (thickest membrane in the body).

It is composed mostly of type 4 collagen fibrils and laminin organized into lamellae, with no elastic fibers (lamellae fibrils give it some elasticity).

Anteriorly, inner surface of capsule is in direct contact with base of anterior epithelial cells. Posteriorly, inner surface of lens capsule is in contact with base of most superficial/outermost/newest set of lens fibers.

This “bumpy” appearance of the capsule may be due to the capsule conforming to the shape of the underlying anterior lens epithelial cells
Equator

Question 13

Compare the thickness of the lens capsule:
Where thickest?
Where thinnest?
Compare anterior vs. posterior capsule: which thickest?

Answer 13

The lens capsule is thicker on its anterior
surface vs. posterior surface, especially if comparing anterior pole (thick) vs. posterior pole (thin).

Thus the anterior capsule continues to thicken with increased age as the anterior epithelium lays down new basement membrane, but there is little change at the posterior pole since there is no longer a posterior lens epithelium to secrete more basement membrane

The anterior & posterior surfaces of the capsule are thicker peripherally in the pre- equatorial & post- equatorial regions and thinner centrally near the two poles & at the equator.

Question 14

What type of epithelium is the anterior lens epithelium?
What does the base of the epithelium lie adjacent to?
What does the apex of the anterior lens epithelium lie adjacent to and how do they interact? Interdigitate? Cell junctions?

Answer 14

Anterior lens epithelium is a single sheet of cuboidal cells (simple cuboidal epithelium) spread over anterior surface of lens and beneath lens capsule.

The base of the epithelial cells lies adjacent to the capsule

Their apical surface faces inward towards the lens fibers.

The lateral membranes of adjacent anterior epithelial cells have complex interdigitations and are held together by desmosomes & many gap junctions

Question 15

Describe what occurs at each zone in the anterior epithelium

Answer 15

CENTRAL ZONE *80% of all anterior lens epith. cells
Stable population of low cuboidal (flattened) cells that cover central region around anterior pole (true aged cells that do not migrate). Normally no mitotic activity.

INTERMEDIATE (PRE-GERMINATIVE) ZONE *peripheral to central zone; mitosis occasionally. New cells only add to anterior epithelium and do not differentiate

GERMINATIVE (PRE-EQUATORIAL) ZONE
major site of cell division; cells formed become new lens fibers. Cells here retain mitotic ability through life, and are smaller/more cuboidal

TRANSITIONAL ZONE
daughter cells of germinative zone migrate posteriorly into transitional zone, start to differentiate into new lens fibers (more ribosomes, microtubules in cytoplasm). Cells differentiate as they get closer to equator: become more columnar, mature, produce crystallins, and elongate.

Question 16

Additionally:
1. Which zone is the major site of cell division?
How long do these cells retain mitotic activity?

2. In which zone will cells occasionally divide to give rise to daughter cells that only become additionally anterior epithelial cells?
   Why are more anterior epithelial cells needed?
3. Where are new lens fibers added to the lens?
4. What is the lens bow and why does it occur?
5. What happens during terminal differentiation of a lens fiber and when does it occur?

Answer 16

1. Germinative (pre-equatorial) zone, retain mitotic ability throughout life
2. Intermediate (pre-germinative) zone. More anterior epithelial cells needed to replace older or damaged epithelial cells, and allow cells to continue to grow
3. New lens fibers are added to the lens just beneath the capsule. The cells have completed changing their orientation as they moved through the zones of the anterior epithelium so that now the apex of the cells face the anterior epithelium & the base of the cells faces the posterior capsule. The new lens fibers get displaced inward (i.e. they are internalized) to lie adjacent to
   the outermost lens fibers already present in the lens and then elongate anteriorly & posteriorly to become lens fibers and thus completely enclose the lens fibers.
4. Note that the newly formed lens fibers still have nuclei and during the elongation process the nuclei assume a more anterior position as the apical end of the lens fibers extend anteriorly.
   – Thus the nuclei of these deeper fibers lie more anterior than the nuclei of more
   superficial lens fibers just being added at the equator. This progressive anterior shift of the nuclei as lens fibers elongate creates the arched arrangement of new lens fibers’ nuclei near the equator called the “lens bow”.
5. Terminal differentiation of the new lens fibers occurs after the lens fibers complete elongation.
   Elongation is completed when the apical end of the new lens fibers break contact with the apical surface of the anterior lens epithelium and the basal end of the new lens fibers break contact with the posterior lens capsule because newer lens fibers lie external to them and these newer lens fibers are now contacting the anterior epithelium and posterior lens capsule.
   During the process of “terminal differentiation” the lens fibers lose their nucleus and organelles (golgi, rER, smooth ER, mitochondria)
   – This is necessary because retention of nuclei & organelles would cause significant diffraction of light & compromise lens function.

Question 17

What is the origin of the zonules? Be specific.
Where do they insert?
What is their relationship to pars plicata?

Answer 17

Zonules originate from the basement membrane of the non- pigmented epithelial cells lining pars plana of the ciliary body, 0.5 - 1mm anterior to the ora serrata

The zonules pass forward towards the lens, passing through the spaces between the ciliary processes of pars plicata between the ciliary processes of pars plicata the zonules are firmly anchored to the basement membrane covering the unpigmented epithelium of the ciliary processes of pars plicata.
– This anchoring allows the zonules to bend and then continue forward at a new, different angle to terminate in the lens capsule as: anterior, posterior & equatorial zonules

Most zonules attach to the lens
capsule at the pre-equatorial and post-equatorial regions while few attach directly at the equator
– Anterior zonules insert up to 1.5 mm anterior to the equator and are the densest bundle of zonules
– Posterior zonules insert ~ 1 mm posterior to the
equator

Question 18

Define and compare dislocation and subluxation of the lens

Answer 18

Dislocation = lens displaced out of the pupil due to complete disruption of the zonules

Subluxation = lens still in the pupil but it is decentered due to disruption of some of the zonules; lens can still accommodate.
– In patients with Marfan’s syndrome the lens is displaced superior- temporally

Question 19

What aging changes occur to the:

• lens thickness
• anterior chamber depth (and why?)
• lens diameter

Answer 19

LENS THICKNESS
The lens capsule at the anterior pole changes, on average, from 11 to 15 μm with increased age.

ANTERIOR CHAMBER DEPTH
There is a forward movement of the lens due to increased size. Anterior chamber depth decreases due to increased lens size.

LENS DIAMETER
(Nasal-temporal dimension): 6.5 mm at birth; ~10 mm in adults

Question 20

Where do congenital cataracts occur in the lens and why?

Answer 20

Congenital cataracts are present at birth, formed during development of embryonic and fetal nucleus so may be seen as opacities associated with Y sutures (fetal nucleus) or seen in the center of lens
(embryonic nucleus)
-usually do not affect vision

Question 21

Name the layers of the adult lens from anterior to posterior.
Be sure to include embryonic, anterior and posterior fetal nucleus, anterior and posterior adult nucleus, anterior and posterior cortex, anterior and posterior lens capsule, anterior lens epithelium where applicable.

Answer 21

anterior lens capsule
anterior lens epithelium
anterior cortex
anterior adult nucleus 
anterior fetal nucleus 
anterior embryonic nucleus 
.... other side ends at posterior lens capsule

Question 22

(CO) 1. Provide a general description of the adult lens in terms of:

• location in the eye and anatomical relationships
• define anterior & posterior pole and equator
• lack of nerve and blood supply
• differences in convexity (steepness) on anterior vs. posterior surface
• how it grows - new fibers located more centrally or more peripherally?

Answer 22

The new lens fibers get displaced inward (i.e. they are internalized) to lie adjacent to
the outermost lens fibers already present in the lens and then elongate anteriorly & posteriorly to become lens fibers and thus completely enclose the lens fibers.
– lens fiber elongation involves increased RNA synthesis as specific structural proteins & cell membrane proteins are formed

**Thus, new lens fibers are added at the equator just beneath the lens capsule
This process occurs all around the equator, with new lens fibers stretching towards the lens poles
The anterior end of the lens fibers will come to lie between the anterior epithelium and the underlying fibers, while the posterior end (base) of the lens fibers ends up lying adjacent to the posterior lens capsule so new lens fibers lie external to the “older outermost” lens fibers but internal to the capsule.

Question 23

(CO) 2. Describe the development of the lens being sure to include:

• embryonic tissue origin
• fate of anterior & posterior epithelium of lens vesicle
• how the lens capsule is formed
• how primary and secondary lens fibers are formed
• which nuclei of the lens have sutures

Answer 23

> Embryonic tissue forming the lens originates from the ectoderm (which forms the lens placode)
optic cup-> lens pit-> lens vesicle (pinches off from surface ectoderm and lies in mesenchyme anterior to optic cup)
Lens vesicle is a hollow sphere lined by single layer of cuboidal cells subdivided into anterior and posterior epithelial cells
Anterior epithelial cells remain in place as the anterior lens epithelium. Posterior epithelial cells lengthen and obliterate cavity of lens vesicle, become the first lens fibers.
Adult lens has no posterior lens epithelium since those were used to form the primary lens fibers. Secondary fibers are formed by multiplication of epithelial cells in pre-equatorial (germinative) region, elongating towards anterior/posterior poles.
Fetal nucleus has sutures.

Question 24

(CO) 3. Describe the lens capsule in terms of:

• location and general composition (type IV collagen & laminin)
• where thicker vs. thinner, differences in thickness at anterior vs. posterior pole, etc.
• defining what it is and which cells secrete it anteriorly and posteriorly
• functions
• appearance of anterior lens capsule with slit lamp (shagreen)

Answer 24

> It surrounds the entire lens, completely
enclosing the anterior lens epithelium & all new and old lens fibers
Mainly composed of type IV collagen fibrils
& laminin organized in layers (lamellae)
Anteriorly the capsule of the lens is secreted and
maintained by the anterior lens epithelium.
The capsule beyond the posterior margin of the lens
epithelium is maintained by the most superficial (outermost) lens fibers (via contributions from their basement membrane).
The lens capsule is thicker on its anterior
surface vs. posterior surface, especially if comparing anterior pole (thick) vs. posterior pole (thin).

Question 25

(CO) 4. Describe the anterior epithelium including:
- histologic classification of the anterior lens epithelium
- zones of the anterior epithelium and what occurs in each zone; what happens when differentiating lens fibers reach equator and what occurs during terminal differentiation & where it occurs
- functions of the epithelium
- types of junctions associated with the epithelium (apical, basal and lateral surfaces, any
zonula occludens junctions at apicolateral border of the cells?)
- how anterior epithelium interacts with adjacent lens fibers to provide nutrients to lens
fibers (via junctions or what?)

Answer 25

Functions of the anterior lens epithelium include:
> production of new lens fibers

> secretion of the lens capsule material (basement membrane of anterior epithelium)

> transport of substances from the aqueous humor to the lens interior to provide nutrients to the lens fibers

> actively pumps water out of the lens to help maintain its transparency (via Na+/K+ATP-ase pump and Ca++ activated pump) and to maintain electrolyte balance

> Lens fibers (whether in the same layer or adjacent layers) are held together by extensive interdigitations of their adjacent plasma membranes and by desmosomes The interdigitations between lens fibers:
– help maintain lens fiber order to maintain lens transparency since irregularities in structure create opacities.
– allow some flexibility of the lens fibers during changes in lens shape as during accommodation

> Lens fibers have gap junctions that allow communication between cells and facilitate movement of nutrients and ions to the lens fibers (including the inner lens fibers)
Most gap junctions are located in the equatorial region of the lens fibers
Additionally, communication occurs between lens fibers via areas of membrane fusion This occurs anteriorly and posteriorly (at the sites of sutures).

Question 26

(CO) 5. Describe the lens fibers in terms of:

• where new fibers are added to lens and elongation occurs
• source of new lens fibers
• fact they form the nucleus and cortex of the lens (differences between embryonic/fetal nucleus in terms of location in lens, which is more internal)
• describing what changes occur to the lens fibers’ nuclei and organelles as the fibers undergo terminal differentiation
• state WHEN terminal differentiation occurs!
• what do the mature lens fibers contain?
• how lens fibers are held together (desmosomes? gap junctions? or what?)
• how lens fibers communicate with each other and what facilitates the flow of nutrients to the lens fibers

Answer 26

> The new lens fibers thus formed are added at the lens equator and then elongate towards the anterior & posterior poles to form new lens fibers that are laid down outer to all earlier fibers.

> Throughout life, additional (secondary) fibers are formed by the multiplication of epithelial cells in the pre-equatorial (germinative) region of anterior epithelium

> The pre- and post- equatorial regions of the capsule are thicker because most lens zonules insert into the lens capsule in these regions (few insert in the region of the equator), thus adding to the capsule’s thickness.

> During the process of “terminal differentiation” the lens fibers lose their nucleus and organelles

> Terminal differentiation of the new lens fibers occurs after the lens fibers complete elongation.

> Lens fibers (whether in the same layer or adjacent layers) are held together by extensive
interdigitations of their adjacent plasma membranes and by desmosomes

> Lens fibers have gap junctions that allow communication between cells and facilitate movement of nutrients and ions to the lens fibers (including the inner lens fibers)… see previous question

Question 27

(CO) 6. Sutures

• define lens sutures and how sutures differ in complexity as a person gets older
• differences between embryonic & fetal nucleus in terms of: associated sutures, lens fibers that formed them (primary or secondary fibers?)
• how you would be able to tell whether you were looking at the embryonic or fetal nucleus with the slit lamp

Answer 27

After birth as the lens enlarges and additional layers of lens fibers added, the sutures become more complex since the Y shape suture is no longer complex enough for the much larger numbers of fibers to attach to one another.

Embryonic nucleus = innermost layer. The lens fibers forming the fetal nucleus meet at “Y” sutures
– The anterior ends meet at an erect “Y” suture
– The posterior ends meet at an inverted “Y” suture

Question 28

(CO) 7. Name (or identify on a picture) the layers of the adult lens from anterior to posterior and be able to relate those structures to an optic section of the lens as discussed in class. Be sure to include embryonic, anterior & posterior fetal nucleus, anterior & posterior adult nucleus, anterior and posterior cortex, anterior and posterior lens capsule, anterior lens epithelium where applicable.

Answer 28

see previous question

Question 29

(CO) 8. Know in which regions of the lens congenital cataracts would be found in an adult lens

Answer 29

They are observed in the embryonic and fetal nucleus of the lens (since these are the parts of the lens formed before birth).

Question 30

(CO) 9. Describe the zonules in terms of:
- specific origin
- insertion points
- how they travel from origin to insertion (relate to ciliary body processes)
- composition
- describe what can happen if zonules ruptured: definition of subluxation and dislocation of
lens and cause!

Answer 30

The lens is attached to the ciliary body by a group of thread-like processes called the zonules (of Zinn) or “suspensory ligament of the lens”.

The zonules pass forward towards the lens, passing through the spaces between the ciliary processes of pars plicata between the ciliary processes of pars plicata the zonules are firmly anchored to the basement membrane covering the unpigmented epithelium of the ciliary processes of pars plicata

Origin = basement membrane of the non- pigmented epithelial cells lining pars plana of the ciliary body

Insertion =
Anteriorly-> anterior to the equator and are the densest bundle of zonules
Posteriorly-> ~ 1 mm posterior to the
equator

Composed of fibrillin (glycoprotein) that aggregates to form a microfibrillar network; does not contain elastin.

Rupture or breaking of the zonules due to trauma, disease or congenital defects may lead to subluxation or dislocation of the lens

Question 31

(CO) 10. How the following lens structures and ocular structures change with age:

• lens fibers - increase or decrease in number?
• diameter of the lens - increase or decrease?
• thickness of the lens - increase or decrease?
• size of the lens
• anterior chamber depth

Answer 31

As new lens fibers are continually added to periphery of the growing lens, the central lens fibers will get compressed in the deeper layers of the lens & although they will lose their nuclei and organelles, they continue to contain much protein in the form of alpha & beta crystallins

Diameter increases; thickness and size increases

Anterior chamber depth decreases