BS - Lens Structure & Metabolism 1 - Week 5 Flashcards
Describe the percentage composition of the human lens.
61% water
33% protein
6% other
Does the lens have any neurovascular supply?
No, it is aneurovascular.
Are lens cells shed?
No, they divide, but are not shed.
What are two age related changes to the lens?
Cataract
Presbyopia
Define the following on a lens:
Anterior/posterior pole
Equator
Anterior pole - centre of the anterior surface
Posterior pole - centre of the posterior pole
Equator - midway between the two poles, where zonules attach
Describe the lens capsule’s structure.
Elastic basement membrane that envelops the lens.
Where on the lens is the capsule thickest?
At the anterior and equatorial surfaces.
What is the dominant collagen type in the lens capsule?
Type IV
Where are the epithelial cells of the lens located?
Beneath the capsule only on the anterior surface.
The lens epithelium is divided into what three regions? Describe the regional variations between them.
Central zone -No division occurs Intermediate zone -Smaller zone, occasional mitosis Germinative zone -Mitosis, elongation, and differentiation occurs here
How do the nuclei appear histologically on a cross section of the lens? Describe why this formation occurs.
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.
Concerning the epithelium, what is vital to maintaining lens transparency?
Gap junctions between cells.
What are the lateral membranes between lens epithelial cells like?
They are highly folded, contributing to the tight connection between them.
What forms the main bulk of the lens?
Lens fibres
What happens to lens fibres as they enter the lens cortex?
They lose their nucleus and organelles, and increase protein synthesis.
What shape do lens fibre cross sections have?
They are hexagonal, and form rows.
Compare the lens diamter anteriorly vs posteriorly. What is the purpose of this?
They are thinner posteriorly, giving the lens its shape.
Where do the tips of the lens fibres meet?
At the sutures.
What structure do the lens sutures have in newborns? What is it like in adults?
Its forms a Y anteriorly, and a ⅄ anteriorly.
In adults, it is highly branched, and the number of arms increases.
Where do zonules of ciliary bodies attach?
The superficial 8-10 layers of the anterior cortex of the lens.
What kind of joint is formed by the zonules and the lens? How do the joints change in deeper layers?
It is a ball and socket joint.
In deeper layers, the joints are smaller.
What are zonules composed of? What is the major collagen type?
Has fibrillar and non-fibrillar components.
Major collagen type is IV
Where do anterior zonules begin and insert to? What diameter do they have?
Runs from the pars plana to the pre-equatorial lens, with large diameters.
Where do posterior zonules begin and insert to? What diameter do they have?
Runs from the pars plicata to the post-equatorial lens, with large diameters.
Where do equatorial zonules begin and insert to? What diameter do they have?
Runs from the pars plicata to the ens equator, with small diameters.
What 3 features of the lens contribute to its transparency?
No organelles/nuclei
No blood supply
No cellular turnover
Does the lens play any role in filtering light?
Yes, it filters out smaller wavelengths that degrade the image.
Where does the lens get its nutrient supply from?
The aqueous humour, providing glucose, ions and lactate.
Are fibre cells alive?
No, they are just sacks of protein
What is the major source of energy for the lens, and what happens in its absence?
Glucose.
Opacity results from its absence.
How does the lens uptake glucose?
Facilitated diffusion
What are the three major metabolic pathways for glucose in the lens?
Glycolysis and TCA cycle
Pentose pathway
Polyol pathway
What percentage of glucose is used in the pentose pathway?
10-20%
What pathway is a major source of lens CO2?
Pentose pathway.
Which pathway is an important source of NADPH?
Pentose pathway.
What is they key purpose of NADPH?
Resisting oxidative stress.
Too much glucose increases activity of which pathway?
Polyol pathway
What happens to excess glucose via what pathway?
Converted to fructose via the polyol pathway.
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?
Accumulation of sorbitol, leading to increased osmotic pressure, leading to sugar cataract.
Important pathway in diabetics.
How does diabetic/sugar cataract appear on a lens?
Snowflake appearance, as it begins primarily at the sutures.
What happens when there isnt enough glucose for the lens?
Cataracts.
What protein channel controls lens ion balance?
What is the movement of ions like?
Na+K+ATPase
Na+ transported into the epithelium from the cortex, and actively exchanged for K+ by ATPase
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+?
- 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
What is the circulation pathway of the lens like?
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.
What does an ionic imbalance result in?
Leads to an influx of water, resulting in cell lysis.
This is called osmotic cataract.
Where does the major protein synthesis in the lens occur?
Equatorial region
What are the three main lens proteins, and what is their purpose?
Needed for the refractive index of the lens.
α-crystallin
β-crystallin
γ-crystallin
How is lens transparency maintained despite the high protein content?
The interactions between the proteins are uniformly distributed, allowing light transmission.
What is the major lens protein? Name its two subunits and their functions.
α-crystallin
αA subunit acts as a chaperone preventing agglutination
αB subunit acts as a heat-shock protein
What is the largest lens protein?
α-crystallin
What percentage of lens protein does the β-crystallin form?`
30%
Where is the β-crystallin formed?
Outer cortex
Which lens protein has the lowest molecular weight?
γ-crystallin
Where are γ-crystallins made, and what does a high γ-crystallin content indicate?
Made prenatally, found in the lens nucleus.
High γ-crystallin indicates a hard lens
What 4 molecules are important for antioxidation in the lens?
Ascorbate
Vitamin C
Vitamin E
Glutathione
Where is glutathione found in high concentrations, and in what form?
Found in the epithelium and the cortex as GSH, its reduced form.
How are glutathione and the pentose phosphate pathway related?
NADPH produced by the pentose pathway reduces the oxidised form of glutathione, GSSG, to its reduced form, GSH.
During natal development, the epithelium of the lens forms on the anterior surface. What happens if the lens is flipped during development?
The epithelium migrates from the posterior surface ,to the anterior surface.
What factor is critical to the lens development, and what 3 processes is it known to cause?
Fibroblast growth factor 2. Known to cause Proliferation Migration Differentiation
Describe the FGF-2 gradient hypothesis.
The concentration increases from anterior to posterior lens, allowing the epithelium to eventually proliferate, migrate and differentiate as it moves posteriorly.
