ophthalamic diseases

Question 1

What is the basic process behind vision?

Answer 1

• rods and cones of the retina receive stimulus and transmit chemical signals to bipolar cells
• these send information to the visual cortex of the brain via the thalamus

Question 2

What kinds of cells are common targets of stem cell therapy in the eye?

Answer 2

• retinal pigment epithelia
• photoreceptors

Question 3

What is the role of retinal pigment epithelium in the eye?

Answer 3

• single layer of cells at the back of the retina
• degeneration of these is the cause of 30% of blindness
• absorbs light and prevents scattering to increase visual accuracy
• also involved in nutrient transport, oxidative stress and act as a physical barrier against new blood cessel formation into the retina from the choroid

Question 4

What is the role of photoreceptors in the eye?

Answer 4

• light detectors
• phototransduction of photons into electrical signals
• cones - colour
• rods - dark nision

Question 5

What is the most common cause of blindess?

Answer 5

• macular degeneration
• this is the part of the retina that gives colour vision

Question 6

What factor effects the pattern of vision loss due to degeneration/fault?

Answer 6

which region or cell type is faulty determines the pattern of vision loss from partial to full

Question 7

What are Stargardt’s disease and AMD?

Answer 7

disorders that affect retinal pigment epithelial cells resulting in photoreceptor death in the macula

Question 8

What are the advantages of targetting macular disease for stem cell therapy over other eye defects?

Answer 8

• high disease burden and visual mortality
• easy to access for intervention
• easily monitored and imaged

Question 9

How can we regenerate retinal pigment epithelial cells with stem cells (in theory)?

Answer 9

• can use embyronal SCs, MSCs from the bone marrow or iPSCs from skin fibroblasts
• differentiate them into retinal pigment epithelium and retinal progenitor cells
• once cells are secreting the correct factors could inject them subretinally to encourage regeneration
• many studies attempting this have yet to show visual improvement

Question 10

What is a factor to consider when deciding if a stem cell therapy is cost effective?

Answer 10

• who is it going to? (i.e. improving quality of life in a child or preserving a small amount of vision in the elderly)
• can it be scale up?

Question 11

What 2 methods are used to deliver stem cells to the retina?

Answer 11

• cells in suspension or sheets
• or in scaffolds - surrounded by amniotic membrane in a pre-made layer injected as one
• acts as a barrier against new blood vessel formation but has not yet been able to improve vision in non-human primates

Question 12

How long does it take to develop differentiated retinal pigment epithelial cells from iPSCs?

Answer 12

up to 10 months

Question 13

What are the success rates like for transplanting progenitor cells into retinal pigment epithelium photoreceptors?

Answer 13

• retinal progenitor cells predominantly differentiate into glial cells with no functional benefit
• mouse studies have shown that the use of photoreceptor precursors may be better at migrating to the correct place, differentiating into the correct cell type and connecting with endogenous cells and signalling pathways

Question 14

What is proof that the eye is not entirely immune privileged from stem cell implantation?

Answer 14

immunosuppression promotes survival and integration of subretinally injected hESC-derived photoreceptors in a canine model