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BMS 114: Stem cells and society > Regeneration strat: Hearing loss > Flashcards

Regeneration strat: Hearing loss Flashcards

1
Q

What are the 5 causes of hearing loss?

A

1) Ageing
2) Genetics
3) Diseases
4) Noise
5) Ototoxic drugs

ALL CAUSE LOSS OF THE OUTER HAIR CELLS

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2
Q

What 3 diseases can cause hearing loss?

A

Mumps

Measles

Meningitis

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3
Q

Can mammals regenerate hair cells when they are lost?

A

No

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4
Q

Can chick regenerate hair cells when they are lost?

A

Yes

- Cells underneath the hair cells transdifferentiate into hair cells (switch fate)

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5
Q

What is sensorineural hearing loss?

A

Hearing loss caused by a lesion or disease of the inner ear or the auditory nerve.

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6
Q

What 4 things can prevent hearing loss?

(eg.when KNOW going to be exposed to loud noice etc.)

A

1) Anti oxidants
2) Growth factors
3) Anti- apoptotic drugs
4) NDMA blockers

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7
Q

Why are the results of hearing loss delayed?

A
  • Notice damage a long time after it has occurred
  • Damage builds up
  • Start to notice frequencies missing such as speech
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8
Q

What do humans produce in the body to limit damage to the hair cells?

A

Antioxidants

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9
Q

What happens during high noise levels?

A

1) IHCs release excess glutamate
2) Excitotoxic damage to the sensory neuron
3) Produce NO
4) Forms peroxynitirite which is toxic

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10
Q

Why are antioxidants important?

A

If have antioxidants- remove oxygen, peroxynitrite cant form, when oxygen reacts with NO

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11
Q

What happens to the levels of antioxidants when age?

A

They decrease

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12
Q

How can hearing loss be recovered with electronic implants? (3 ways)

A

1) Cochlear implant
(most effective)

2) Auditory nerve implant
3) Brainstem implant

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13
Q

What does the cochlear implant by pass?

A

Hair cells

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14
Q

What does auditory nerve implant bypass?

A

The cochlear

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15
Q

What does the brainstem implant bypass?

A

The cochlear and auditory nerve

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16
Q

How do cochlear nerve implants work

A
  • Speech processor on the ear
  • Electrode threaded into the cochlear and cochlear spirals
  • Near to the hair cells, turn sound into electrical impulses
  • Stimulating nerve directly
17
Q

What are the disadvantages of cochlear implants?

A
  • Need to have intact nerve for it to work

- Number of people in which the cochlear nerve dies back when get loss of hair cells

18
Q

How could the disadvantage of cochlear implants be overcome?

A

Regrow the cochlear nerve using:

1) ES cells into spiral ganglion nerve
2) Growth factors

19
Q

Where does the electrode of the brainstem implant go to?

A
  • Cochlear nucleus (where the spiral ganglia normally innovates)
20
Q

Why do the hair cells in mammals not regenerate when they are damages?

A
  • Favour fast repair over proper regeneration

- SO Inhibitory factors made, preventing proper functional repair

21
Q

How could regeneration be induced in mammals?

A
  • By interfering with the inhibitory factors produced
  • Might allow regeneration by:
    1) Allowing an environment for transplanted stem cells to proliferate

OR

2) allowing transdifferentiation

22
Q

Are there stem cells in the ear underneath the hair cells in mammals?

A

No

23
Q

What happens when the retinoblastoma1 gene is deleted and why?

A
  • Hair cell proliferation (and then deletion)

- In the cell cycle, the Rb protein must be removed from E2F to allow gene transcription

24
Q

What is ATOH1 (math1)?

A

A transcription factor critical for the development of the cochlear and vestibular system

  • Can be transfected into hair cells
25
Q

In mammals, what occurs in the hair cells/supporting cells regarding notch signalling?

A

1) Hair cell makes notch ligand
2) Notch receptor is cleaved by gamma-secretase turns on Hes genes in the supporting cells
3) Hes represses Atoh1 (transcription factor that dives development of hair cells etc)

26
Q

What experiment is done in the mouse to test reactivation by manipulating notch signalling?

A

1) Deafen animals using drugs
2) Add gamma-secretase INHIBITORS
3) Notch not cleaved, Atoh1 expression released
4) Saw regeneration of hair cells

27
Q

What is the problem with using notch manipulation?

A
  • Stimulates the OHCs

- Need to make IHCs as well

28
Q

Can ES cells be differentiated into hair cells?

A

Yes

  • But much easier in mice than humans
29
Q

What are the problems with cell transplantaation to the auditory nerve?

A

1) Scar tissue

2) Donor cell:
- Source
- Characterisation
- Quality

3) Cell devlivery
- Surgery
- Collateral damage

BMS 114: Stem cells and society (15 decks)

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