Regeneration of optics nerves -- How?

[LightningInAJar]

TL;DR Summary

How can Yamanaka factors initiate regeneration?

https://www.science.org/content/art...ost-sight-mice-offering-clues-reversing-aging

I understand that they used 3 of 4 Yamanaka factors to reverse the epigenetic profile of certain cells in the optic nerve, but what caused an apparent regeneration of the nerve? I can understand changing something informational to a younger version, but that shouldn't cause anything new to happen that the body simply doesn't do normally?

 

[BillTre]

The argument seems to be that the by changing what genes the ganglion cells can express (by the manipulation of metagenomic things that affect the cell's ability to express particular genes), the cells acquires new possible behaviors (like being able to regenerate).
The set of genes a cell can express is thought to define what the cell is capable of doing.
Generally this is similar to the transcriptome (set of genes expressed) but it more like a potential transcriptome.

Being able to express different genes would be expected to change what the ganglion cells would be able to to do (in response to some pathological situation).
The pathological situation would provide the cells some trigger stimulus to initiate a response, like regeneration, in the ganglion cells. This could invoke gene expression and behaviors that would not happen in normal situations not involving regeneration.
This might that might involve the cell reverting to gene expression patterns the cells might have used wen they were first developing in an embryo.
Alternatively, adult cells may have to produce a different set of genes to better regenerate in the adult situation (adults are different from embryos).

In addition to the ganglion cells, there are other cells that would be involved in optic nerve regeneration. Besides the axons of the optic nerve, there are other cells (like glial cells) that provide mechanical and physiological support to the axons.
What these glial cells do, and the state they are in, can affect the potential success of any potential optic nerve regeneration which would also involves the state of the ganglion cells.
How the non-ganglion cells in the optic nerve affect regeneration is different in different species. Frogs for example, are great regenerators.

 

[jim mcnamara]

Did you ever wonder why the same DNA creates bone cells in one instance and heart tissue in another?
Every biologist I've known certainly has. Me included. It has a name: cell differentiation. The cause may be so-called epigenetics. What you and @BillTre are discussing.

The answer seems to lie in the fact that there are "switches" that can moderate (kind of like a volume knob ), or turn off, or turn on sets of genes so they can do this trick of making the right cell types in the right places.

The switches are thought to be kinds small molecules called:
methyl groups
histones
Suppressor proteins

When you look at DNA in human eggs or sperm cells you find none of these molecules attached to DNA. They accumulate as you mature, and along the they also get stuck onto not-so-great, more or less random places on DNA. As you hit advanced age the extra "stuck-ons" can accumulate too much. The effect can be detrimental.

A very revealing test is to look at DNA from identical twins in their later years. The epigenetic effects of living result in different DNA patterns of stuck-on molecules. The DNA started out the same.
https://en.wikipedia.org/wiki/Epigenetics

 

[LightningInAJar]

Did you ever wonder why the same DNA creates bone cells in one instance and heart tissue in another?
Every biologist I've known certainly has. Me included. It has a name: cell differentiation. The cause may be so-called epigenetics. What you and @BillTre are discussing.

The answer seems to lie in the fact that there are "switches" that can moderate (kind of like a volume knob ), or turn off, or turn on sets of genes so they can do this trick of making the right cell types in the right places.

The switches are thought to be kinds small molecules called:
methyl groups
histones
Suppressor proteins

When you look at DNA in human eggs or sperm cells you find none of these molecules attached to DNA. They accumulate as you mature, and along the they also get stuck onto not-so-great, more or less random places on DNA. As you hit advanced age the extra "stuck-ons" can accumulate too much. The effect can be detrimental.

A very revealing test is to look at DNA from identical twins in their later years. The epigenetic effects of living result in different DNA patterns of stuck-on molecules. The DNA started out the same.
https://en.wikipedia.org/wiki/Epigenetics

I thought even epigenetics has a hereditary component and can be attached to DNA from the start? (Perhaps minimized a bit)

 

[LightningInAJar]

The argument seems to be that the by changing what genes the ganglion cells can express (by the manipulation of metagenomic things that affect the cell's ability to express particular genes), the cells acquires new possible behaviors (like being able to regenerate).
The set of genes a cell can express is thought to define what the cell is capable of doing.
Generally this is similar to the transcriptome (set of genes expressed) but it more like a potential transcriptome.

Being able to express different genes would be expected to change what the ganglion cells would be able to to do (in response to some pathological situation).
The pathological situation would provide the cells some trigger stimulus to initiate a response, like regeneration, in the ganglion cells. This could invoke gene expression and behaviors that would not happen in normal situations not involving regeneration.
This might that might involve the cell reverting to gene expression patterns the cells might have used wen they were first developing in an embryo.
Alternatively, adult cells may have to produce a different set of genes to better regenerate in the adult situation (adults are different from embryos).

In addition to the ganglion cells, there are other cells that would be involved in optic nerve regeneration. Besides the axons of the optic nerve, there are other cells (like glial cells) that provide mechanical and physiological support to the axons.
What these glial cells do, and the state they are in, can affect the potential success of any potential optic nerve regeneration which would also involves the state of the ganglion cells.
How the non-ganglion cells in the optic nerve affect regeneration is different in different species. Frogs for example, are great regenerators.

Interesting. I think they chose the eye because it tends to be biologically separate from the body and even has barriers from the brain to a degree as well. But is there any reason to believe the same type of regeneration couldn't be possible in the cervical spine? Say there are bone spurs and stenosis putting dangerous pressure on the nerves and typical spinal surgeries are archaic and risky? A guided bone remodeling.

 

[BillTre]

I think they chose the eye because it tends to be biologically separate from the body and even has barriers from the brain to a degree as well.

There are several advantages to studying optic nerve regeneration vs. that in the spinal cord, including:

• There is a lot of funding for eye research.
• There are well built up bodies of knowledge about the optic nerve (possibly more than for the spinal cord). These bodies of knowledge allows better experiments.
• There is a lot of potential benefit to the findings about the eye.
• The optic nerve is a much simpler cellular system than the spinal cord. There are way fewer different neurons involved and probably a more homogeneous collection of glia cells.
• In this case you cited, they are a relatively non-invasive way to cause the optic nerve damage (injecting micro-beads) that they then wanted to fix. This makes the experiment easier and cleaner to perform.
• The retinal ganglion cells are a nice pretty pure population of cells that can be easily treated by eye injections.

But is there any reason to believe the same type of regeneration couldn't be possible in the cervical spine?

There are lots of different differences in different species.
Regeneration can happen in a variety of places in different species.
There are no rules for all locations in all species.

Say there are bone spurs and stenosis putting dangerous pressure on the nerves and typical spinal surgeries are archaic and risky? A guided bone remodeling.

I had a friend with a bone spur putting pressure of his spinal cord at times.
He had the bone spurs removed and got a lot better.

 

[LightningInAJar]

There are several advantages to studying optic nerve regeneration vs. that in the spinal cord, including:

• There is a lot of funding for eye research.
• There are well built up bodies of knowledge about the optic nerve (possibly more than for the spinal cord). These bodies of knowledge allows better experiments.
• There is a lot of potential benefit to the findings about the eye.
• The optic nerve is a much simpler cellular system than the spinal cord. There are way fewer different neurons involved and probably a more homogeneous collection of glia cells.
• In this case you cited, they are a relatively non-invasive way to cause the optic nerve damage (injecting micro-beads) that they then wanted to fix. This makes the experiment easier and cleaner to perform.
• The retinal ganglion cells are a nice pretty pure population of cells that can be easily treated by eye injections.

There are lots of different differences in different species.
Regeneration can happen in a variety of places in different species.
There are no rules for all locations in all species.
I had a friend with a bone spur putting pressure of his spinal cord at times.
He had the bone spurs removed and got a lot better.

That is good to hear about your friend. I have largely heard about surgeons fusing bones together, extracting discs, inserting artificial discs that don't work well, or creating microfractures in bone to prompt fibrocartilage growth which isn't very good. Stanford at least in mouse small bones might have regenerated natural cartridge, but that could be decades away for humans. I was just wondering if Yamanaka factors could regenerate bones to their natural shape, and regenerate new cartilage from that bone creating basically a fresh new spine. I don't know how selective that experiment can be done, but surgery seems risky and not something I think my doctor would offer me as an option until I lose feeling in my limbs and start peeing myself. I also have retina damage so hopefully that research could go further into the eye than just the optic nerve.

 

[BillTre]

@LightningInAJar, your situation sounds complicated.
You'd be better off talking with a doctor.

 

[LightningInAJar]

@LightningInAJar, your situation sounds complicated.
You'd be better off talking with a doctor.

Did that Yamanaka factor experiment extend to regeneration of the retina as well, or just the optic nerve? How old is your friend? I'm 41 and only was diagnosed with cervical bone spurs this year, and PT hasn't been terribly useful in the long run.

 

[BillTre]

Did that Yamanaka factor experiment extend to regeneration of the retina as well, or just the optic nerve?

I have no idea. Your could try googling this on google scholar.

How old is your friend? I'm 41 and only was diagnosed with cervical bone spurs this year, and PT hasn't been terribly useful in the long run.

Age? don't remember. probably 40's or 50's.
PT did not do much for him because PT is not going to do anything about a piece of bone pressing on your spinal cord (lower down his back vs. yours).
Once that was diagnosed (MRI probably), the course of action was obvious (surgical removal of spur).

 

[LightningInAJar]

Yeah. I wonder what PT is good for except temporarily relief. Traction helped for a little bit. I worry they might argue that removing the bone spurs isn't worth the risks if perhaps my cartilage isn't thick enough to prevent reoccurring. If only Dr. Strange were my surgeon. Lol. Thanks for your insights. They were enlightening.

 

[BillTre]

PT works well for some things.
I have a muscle problem last year with was fixed once the proper PT was figured out.
It depends on what the problem is. Diagnosis is important.