Regeneration strat: Hearing loss Flashcards
What are the 5 causes of hearing loss?
1) Ageing
2) Genetics
3) Diseases
4) Noise
5) Ototoxic drugs
ALL CAUSE LOSS OF THE OUTER HAIR CELLS
What 3 diseases can cause hearing loss?
Mumps
Measles
Meningitis
Can mammals regenerate hair cells when they are lost?
No
Can chick regenerate hair cells when they are lost?
Yes
- Cells underneath the hair cells transdifferentiate into hair cells (switch fate)
What is sensorineural hearing loss?
Hearing loss caused by a lesion or disease of the inner ear or the auditory nerve.
What 4 things can prevent hearing loss?
(eg.when KNOW going to be exposed to loud noice etc.)
1) Anti oxidants
2) Growth factors
3) Anti- apoptotic drugs
4) NDMA blockers
Why are the results of hearing loss delayed?
- Notice damage a long time after it has occurred
- Damage builds up
- Start to notice frequencies missing such as speech
What do humans produce in the body to limit damage to the hair cells?
Antioxidants
What happens during high noise levels?
1) IHCs release excess glutamate
2) Excitotoxic damage to the sensory neuron
3) Produce NO
4) Forms peroxynitirite which is toxic
Why are antioxidants important?
If have antioxidants- remove oxygen, peroxynitrite cant form, when oxygen reacts with NO
What happens to the levels of antioxidants when age?
They decrease
How can hearing loss be recovered with electronic implants? (3 ways)
1) Cochlear implant
(most effective)
2) Auditory nerve implant
3) Brainstem implant
What does the cochlear implant by pass?
Hair cells
What does auditory nerve implant bypass?
The cochlear
What does the brainstem implant bypass?
The cochlear and auditory nerve
How do cochlear nerve implants work
- 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
What are the disadvantages of cochlear implants?
- 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
How could the disadvantage of cochlear implants be overcome?
Regrow the cochlear nerve using:
1) ES cells into spiral ganglion nerve
2) Growth factors
Where does the electrode of the brainstem implant go to?
- Cochlear nucleus (where the spiral ganglia normally innovates)
Why do the hair cells in mammals not regenerate when they are damages?
- Favour fast repair over proper regeneration
- SO Inhibitory factors made, preventing proper functional repair
How could regeneration be induced in mammals?
- 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
Are there stem cells in the ear underneath the hair cells in mammals?
No
What happens when the retinoblastoma1 gene is deleted and why?
- Hair cell proliferation (and then deletion)
- In the cell cycle, the Rb protein must be removed from E2F to allow gene transcription
What is ATOH1 (math1)?
A transcription factor critical for the development of the cochlear and vestibular system
- Can be transfected into hair cells
In mammals, what occurs in the hair cells/supporting cells regarding notch signalling?
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)
What experiment is done in the mouse to test reactivation by manipulating notch signalling?
1) Deafen animals using drugs
2) Add gamma-secretase INHIBITORS
3) Notch not cleaved, Atoh1 expression released
4) Saw regeneration of hair cells
What is the problem with using notch manipulation?
- Stimulates the OHCs
- Need to make IHCs as well
Can ES cells be differentiated into hair cells?
Yes
- But much easier in mice than humans
What are the problems with cell transplantaation to the auditory nerve?
1) Scar tissue
2) Donor cell:
- Source
- Characterisation
- Quality
3) Cell devlivery
- Surgery
- Collateral damage
