Therapeutic approaches to reversing sensory loss

Why is the eye a good target for therapy? ( 4 points)

• 2 eyes (test + control)

• immune privileged ( eyes have reduced immune response)

• visible through window

• small area → small dose.

Macular degeneration

• what is age related macular degeneration (AMD)

• what does it do

• Degeneration of the macula → loss of central vision.

• High acuity central vision (cone-rich).

What is wet AMD?

• is there a treatment? if so what is it

What is wet AMD?
Abnormal blood vessel growth + leakage → rapid vision loss.

treatment: anti-VEGF injections

( because VEGF stimulates new blood vessel growth )

What is dry AMD?

• is there a treatment? if so what is it

Drusen deposits under retina → slow vision loss.

Treatment for dry AMD?
None.

what are the layers to the macula

retina

RPE ( retinal pigment epithelium)

choroid

retinal pigment epithelium

• what is its role?

• name 2 functions

What is the role of the RPE?
Supports photoreceptors and maintains retinal health.

Functions of RPE?
Blood-retina barrier
Transport (nutrients/ions/water)

Two experimental surgeries for AMD?

• what are they

• what is a problem with them ..

• Macular translocation ( moving macular to healthier part of RPE)

• Autologous transplantation (healthy RPE transplanted on from same patient)

but… this is complex and high risk , only for late stage disease

Stem cell therapy for AMD

• What cells are used for AMD therapy?

• 2 Key properties of stem cells?

• where does it come from

What cells are used for AMD therapy?
Human embryonic stem cells → RPE cells.

properties:

Self-renewal + ability to differentiate.

where does it come from

Inner cell mass of 5-day blastocyst.

Making RPE from stem cells

• how are stem cells turned into RPE

• what do they look like

How are stem cells turned into RPE?
Remove pluripotency (specialising) factors → differentiate.

What do stem-cell-derived RPE cells look like?
Pigmented cobblestone monolayer.

How do we confirm cells are RPE?(2 things)

• pcr (polymerase chain reaction)→check express genes we expect

• immunocytochemistry. → check express the proteins we expect

How do we test if the RPE cells work?

Check the phagocytose photoreceptor debris.

Two ways to deliver RPE cells?

• Injection (of cell suspension)

• Transplant (patch/monolayer)

note: cell suspension = celll floating in liquid

injection

• advantage and disadvantage

Advantage
Simple procedure.

Disadvantage
Cells may not form monolayer.

transplant patch

• advantage and disadvantage

Advantage
Mature organised monolayer.

Disadvantages
Immune response + complex logistics.

mature in this context = already fully formed cells

immune response = body make attack it

complex logistics = difficult to perform

describe the procedure for inserting graft into eye ( 5 steps)

slit cut in eye → flush vitreous body → create blister between choroid and retina → insert patch in blister→ remove fluid from blister to hold patch.

remember: Sexy Fish Can Ignore Ragebait

How do we check patch quality? ( 2 points)

80% coverage
Cobblestone morphology.

why did the clinical trial use wet amd patients

the degradation is fast so they have more intact photoreceptors ( that we can save).

note in AMD, retina/rpe damage = photoreceptors lose support and nutrients = die = central visual field loss)

What are inherited retinal diseases (IRDs)?

• Two types of heterogeneity in inherited retinal disease?

What are inherited retinal diseases (IRDs)?
Genetic disorders causing retinal degeneration.

Two types of heterogeneity ( differences) in IRD?
Genetic heterogeneity → different genes cause same disease
Phenotypic heterogeneity → same gene causes different diseases.