BS - Lens Structure & Metabolism 1 - Week 5

Question 1

Describe the percentage composition of the human lens.

Answer 1

61% water
33% protein
6% other

Question 2

Does the lens have any neurovascular supply?

Answer 2

No, it is aneurovascular.

Question 3

Are lens cells shed?

Answer 3

No, they divide, but are not shed.

Question 4

What are two age related changes to the lens?

Answer 4

Cataract

Presbyopia

Question 5

Define the following on a lens:
Anterior/posterior pole
Equator

Answer 5

Anterior pole - centre of the anterior surface
Posterior pole - centre of the posterior pole
Equator - midway between the two poles, where zonules attach

Question 6

Describe the lens capsule’s structure.

Answer 6

Elastic basement membrane that envelops the lens.

Question 7

Where on the lens is the capsule thickest?

Answer 7

At the anterior and equatorial surfaces.

Question 8

What is the dominant collagen type in the lens capsule?

Answer 8

Type IV

Question 9

Where are the epithelial cells of the lens located?

Answer 9

Beneath the capsule only on the anterior surface.

Question 10

The lens epithelium is divided into what three regions? Describe the regional variations between them.

Answer 10

Central zone
-No division occurs
Intermediate zone
-Smaller zone, occasional mitosis
Germinative zone
-Mitosis, elongation, and differentiation occurs here

Question 11

How do the nuclei appear histologically on a cross section of the lens? Describe why this formation occurs.

Answer 11

It has a hairpin formation.
As the cells migrate to the equator, they elongate once they reach it, and the nucleus is drawn anteriorly, resulting in a hairpin look.

Question 12

Concerning the epithelium, what is vital to maintaining lens transparency?

Answer 12

Gap junctions between cells.

Question 13

What are the lateral membranes between lens epithelial cells like?

Answer 13

They are highly folded, contributing to the tight connection between them.

Question 14

What forms the main bulk of the lens?

Answer 14

Lens fibres

Question 15

What happens to lens fibres as they enter the lens cortex?

Answer 15

They lose their nucleus and organelles, and increase protein synthesis.

Question 16

What shape do lens fibre cross sections have?

Answer 16

They are hexagonal, and form rows.

Question 17

Compare the lens diamter anteriorly vs posteriorly. What is the purpose of this?

Answer 17

They are thinner posteriorly, giving the lens its shape.

Question 18

Where do the tips of the lens fibres meet?

Answer 18

At the sutures.

Question 19

What structure do the lens sutures have in newborns? What is it like in adults?

Answer 19

Its forms a Y anteriorly, and a ⅄ anteriorly.

In adults, it is highly branched, and the number of arms increases.

Question 20

Where do zonules of ciliary bodies attach?

Answer 20

The superficial 8-10 layers of the anterior cortex of the lens.

Question 21

What kind of joint is formed by the zonules and the lens? How do the joints change in deeper layers?

Answer 21

It is a ball and socket joint.

In deeper layers, the joints are smaller.

Question 22

What are zonules composed of? What is the major collagen type?

Answer 22

Has fibrillar and non-fibrillar components.

Major collagen type is IV

Question 23

Where do anterior zonules begin and insert to? What diameter do they have?

Answer 23

Runs from the pars plana to the pre-equatorial lens, with large diameters.

Question 24

Where do posterior zonules begin and insert to? What diameter do they have?

Answer 24

Runs from the pars plicata to the post-equatorial lens, with large diameters.

Question 25

Where do equatorial zonules begin and insert to? What diameter do they have?

Answer 25

Runs from the pars plicata to the ens equator, with small diameters.

Question 26

What 3 features of the lens contribute to its transparency?

Answer 26

No organelles/nuclei No blood supply No cellular turnover

Question 27

Does the lens play any role in filtering light?

Answer 27

Yes, it filters out smaller wavelengths that degrade the image.

Question 28

Where does the lens get its nutrient supply from?

Answer 28

The aqueous humour, providing glucose, ions and lactate.

Question 29

Are fibre cells alive?

Answer 29

No, they are just sacks of protein

Question 30

What is the major source of energy for the lens, and what happens in its absence?

Answer 30

Glucose. | Opacity results from its absence.

Question 31

How does the lens uptake glucose?

Answer 31

Facilitated diffusion

Question 32

What are the three major metabolic pathways for glucose in the lens?

Answer 32

Glycolysis and TCA cycle Pentose pathway Polyol pathway

Question 33

What percentage of glucose is used in the pentose pathway?

Answer 33

10-20%

Question 34

What pathway is a major source of lens CO2?

Answer 34

Pentose pathway.

Question 35

Which pathway is an important source of NADPH?

Answer 35

Pentose pathway.

Question 36

What is they key purpose of NADPH?

Answer 36

Resisting oxidative stress.

Question 37

Too much glucose increases activity of which pathway?

Answer 37

Polyol pathway

Question 38

What happens to excess glucose via what pathway?

Answer 38

Converted to fructose via the polyol pathway.

Question 39

What can increased activity of the polyol pathway lead to an accumulation of, and what is a consequence of this? Which population is this of particular importance in?

Answer 39

Accumulation of sorbitol, leading to increased osmotic pressure, leading to sugar cataract. Important pathway in diabetics.

Question 40

How does diabetic/sugar cataract appear on a lens?

Answer 40

Snowflake appearance, as it begins primarily at the sutures.

Question 41

What happens when there isnt enough glucose for the lens?

Answer 41

Cataracts.

Question 42

What protein channel controls lens ion balance? | What is the movement of ions like?

Answer 42

Na+K+ATPase | Na+ transported into the epithelium from the cortex, and actively exchanged for K+ by ATPase

Question 43

Consider the balance of ions in the lens. What is the levels of Na+ and K+ like in the lens, what is the charge of the lens like, and what is the net flow of K+ and Na+?

Answer 43

- Low Na+ and high K+ in the lens - Interior of the lens is more negative than outside - Na+ passively diffuses through the posterior capsule, actively pumped anteriorly - K+ diffuses into the vitreous humour

Question 44

What is the circulation pathway of the lens like?

Answer 44

Consider a cross section. Divided into four quadrants, the flow would run out of the equator, out and around the lens to the pole, and back out the equator.

Question 45

What does an ionic imbalance result in?

Answer 45

Leads to an influx of water, resulting in cell lysis. | This is called osmotic cataract.

Question 46

Where does the major protein synthesis in the lens occur?

Answer 46

Equatorial region

Question 47

What are the three main lens proteins, and what is their purpose?

Answer 47

Needed for the refractive index of the lens. α-crystallin β-crystallin γ-crystallin

Question 48

How is lens transparency maintained despite the high protein content?

Answer 48

The interactions between the proteins are uniformly distributed, allowing light transmission.

Question 49

What is the major lens protein? Name its two subunits and their functions.

Answer 49

α-crystallin αA subunit acts as a chaperone preventing agglutination αB subunit acts as a heat-shock protein

Question 50

What is the largest lens protein?

Answer 50

α-crystallin

Question 51

What percentage of lens protein does the β-crystallin form?`

Answer 51

30%

Question 52

Where is the β-crystallin formed?

Answer 52

Outer cortex

Question 53

Which lens protein has the lowest molecular weight?

Answer 53

γ-crystallin

Question 54

Where are γ-crystallins made, and what does a high γ-crystallin content indicate?

Answer 54

Made prenatally, found in the lens nucleus. | High γ-crystallin indicates a hard lens

Question 55

What 4 molecules are important for antioxidation in the lens?

Answer 55

Ascorbate Vitamin C Vitamin E Glutathione

Question 56

Where is glutathione found in high concentrations, and in what form?

Answer 56

Found in the epithelium and the cortex as GSH, its reduced form.

Question 57

How are glutathione and the pentose phosphate pathway related?

Answer 57

NADPH produced by the pentose pathway reduces the oxidised form of glutathione, GSSG, to its reduced form, GSH.

Question 58

During natal development, the epithelium of the lens forms on the anterior surface. What happens if the lens is flipped during development?

Answer 58

The epithelium migrates from the posterior surface ,to the anterior surface.

Question 59

What factor is critical to the lens development, and what 3 processes is it known to cause?

Answer 59

``` Fibroblast growth factor 2. Known to cause Proliferation Migration Differentiation ```

Question 60

Describe the FGF-2 gradient hypothesis.

Answer 60

The concentration increases from anterior to posterior lens, allowing the epithelium to eventually proliferate, migrate and differentiate as it moves posteriorly.