Regeneration strat: Age-related macular degeneration

Question 1

What is AMD?

Answer 1

A medical condition which may result in blurred or no vision in the center of the visual field

• Due to the loss of the retinal epithelial cells, which normally provides nourishment to the rods and cones

Question 2

What are the affects of AMD on vision?

Answer 2

• Slow recovery of visual function after exposure to bright light
• Visual activity drastically decreasing
• Blurred vision
• Trouble discerning colours
  (Loss in contrast sensitivity)

Question 3

What is wet AMD characterised by?

Answer 3

• The growth of new blood vessels within the retinal tissue and subsequent haemorrahging from them
• Drusen speads over large parts of the eye

Question 4

What is dry AMD?

Answer 4

-Little of no haemorrhaging

Question 5

What are the early signs of both AMD types?

Answer 5

Drusen
- Fatty deposits on the retina

• Extracellular material builds up between Bruch’s membrane and the retinal pigment epithelium of the eye

Question 6

What are the rods of the eye?

Answer 6

Photoreceptors for low light vision

Question 7

What are the cones of the eye?

Answer 7

Photoreceptors for colour vision

Question 8

What is the macula of the eye?

Answer 8

• Functional centre of the retina

- Gives the best colour vision

Question 9

What is the foeva of the eye?

Answer 9

• Closely packed cones
• Accurate vision
• Centre of the macula

Question 10

What happens during the progression of AMD?

Answer 10

1) Retinal pigment epithelium (RPE) cells towards the rear of the retina malfunction and die
2) Photoreceptors adjacent to the RPE die (can’t be properly supported)
3) Choroid layer containing blood vessels develops abnormal structure and physically displaces overlying neural retina

Question 11

What are 6 functions of the RPE?

Answer 11

1) Regeneration of bleached opsins
2) Phagocytosis of photoreceptor membranes
3) Transepithelial transport
4) Secretion of growth factors essential for the retina
5) Absorption of light
6) Protection against photo-oxidation

Question 12

Can cell transplantation cure AMD?

What type of transplantation was used first?

Answer 12

Yes, possibly
- Restores sight

• Autologous (cells obtained from the same individual)

Question 13

Disadvantages of autologous transplantation to cure AMD?

Answer 13

1) Restoration of central vision is at expense of an area of peripheral vision
2) Lengthy and challenging operation
3) Follow up surgical procedure to remove compression medium

Question 14

Can cultured RPE cell be grown to treat AMD?

Answer 14

Probably

- In vitro produced human RPE maintains sight when transplanted in RCS raat

Question 15

If cultured RPE cells work, what is the problem?

Answer 15

• Donor material hard to come by
• RPE cells show a limited capacity to proliferate in vitro
• RPE phenotype tends to degenerate with time in culture
• Karyotypically abnormal
• Similarity to normal RPE is questionable

Question 16

What other routes, apart from a donor, exist to generate RPE cells in vitro?

Answer 16

1) hESC - look almost identical to RPE cells

2) Patient specific iPS cells (patient specific)?

Question 17

Why is it difficult to deliver the stem cells to the eye?

Answer 17

• Patients typically elderly so have an ages Bruchs membrane

- Cell suspensions may fail to attach to the Bruchs membrane

Question 18

How would you deliver stem cells to the diseased area of the eye?

Answer 18

Must manufacture an artificial membrane (coat a patch with RPE cells)

Question 19

Where is the Bruch’s membrane in the eye?

Answer 19

Beneath the retinal epithelium cells