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Post Info TOPIC: conference in France...news on genetic link & news on intacs


Executive

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Posts: 437
Date: Sun Sep 11 1:27 AM, 2005
RE: conference in France...news on genetic link & news on intacs
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Well guys, I found some other data. they are more structural, if you wish.

Any collagen fiber or fibril or lamela or bundle is covered by a coating or cusion of proteoglycans (another macromolecule). Please read this
please clicl here
It looks like in the stroma 40% of volume are taken by collagen, 50% of proteoglycanes, 5%-9% by other smaller molecules and the very rest, 1% - keratocytes (data from another article, do not remember which). What is very important is that the proteoqlycans cover or cusion is very liophylic or hydrophylic (likes or adsorbs water), gel-like structure, that normally captures great ammounts of water molecules and thus swells. This gel-like watery cusion repels and keeps collagen bundles stable and is, imho, a major contributor to the corneal shape. Now, the water is pumped away from the cornea via endothelium. This is the output of the water. The input comes through the epithelium, no? Now, acording to the above study on aquaporine 5 lack in the epithelium cells we may state that obviously not as many water comes inside a KC cornea as inside a normal one. But as much is pumped away via endothelium. So the gel-like proteoglycans cushion drastically diminish its volume in our corneas, collagen fibres thus become closer to each other. Moreover, as I remeber from the article about x_ray difraction of the KC corneas, there are bundles that run perpendicularly to its surface, or not paralel anyway. This way they are nautarrly pulled off from their anchors in limbus, causing the thinning of the peripheral cornea. And this may explain everything that we are having so far.

IMHO, this study about AQP5 lack, along with the x_ray difraction reslusts on the collagen diosrdering, is one of the majour discoveries on KC. In this way, probably the treatment lies in introducing AQP5 artificially in epithelium cells. Or probably there will a genetic therapy. But so far, the only method that resists these water depletion forces is x_linking, imho...

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yarsky
Anonymous

Date: Sun Sep 11 12:55 PM, 2005
RE: conference in France...news on genetic link & news on intacs
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World-Class Yarsky!!

Just two points i wanted to say in addition to your very thoughtful post...

The genes connection may be can be done through gene therapy (suppressing/stimualeing the identified genes) or re-activating the genes as in the stem cell topic, where stem cells place on the damaged cornea, where by the host cornea regenerates from the sheet of stem cells placed on the host cornea.

Both methgods are on the cards, but (and its a big but) the cells may come back to life but will the cone be reversed due to mechanical reasons?

I think x linking is the only way to mechanically/physically to stop kc as we know it...

To me x linking is just like the finest mesh network you can get to stabize the cornea, in the most minimal was possible.

I think any gene advances to treat the cornea can go hand in hand with x linking...

Great post (BTW i did read that someone drank a lot of water, and there cones reduced?)

-- Edited by QuintriX at 12:57, 2005-09-11

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Executive

Status: Offline
Posts: 437
Date: Sun Sep 11 10:54 PM, 2005
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I think the process is irreversible (collagen bundels can not anchor themselves back into limbus...) Many questions...it is very complex. the picture is complex and there are many facets...We need to find a state of the art book about how does the cornea and things around function....So far the treatment can be only preventive. All these water and ion transport questions are still not clear. AQP5 comes to the epithelium from lacrimal glande...More research should come on this in the nearest future, that's my feeling, it's on the run. The treatment can be only preventive so far, like x_linking. Any way, even if you drink more water it can hardly get inside the cornea (with tears) through epithelium since not enough water chanels to let it in. Well this is obscure, this process of water getting in: cells take it in and than out in another direction? Need to do more reading...

Well imagine, AQPs are synthesised elswhere and then introduced onto the epithelium as eye drops. Suppose this helps water to go in. There proteogycans do capt it, the coating swels andl increases its volume and thus push the collagen bundels, repel them in all or not all directions. This process may add some bulk to the thined cornea. But I think it will be very hard (impossible) to move them back, to the positions where theye were before they sturted to collapse. Very schematicaly. That's why the treatment should be as early as possible.

-- Edited by Yarsky at 23:05, 2005-09-11

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yarsky
Anonymous

Date: Sun Sep 11 11:41 PM, 2005
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Thanks for your thoughts... I do agree with you... i have this funny feeling that x linking alone done early will not create any other problems with your kc with regards to the non-obvious things like further thinning, degeneration... as seen with people with mild kc which has stopped... do you see what mean... i mean not only is kc stopped so is any hydrops? (to be honest i think flat fitting hard lenses on an advanced weak cornea is to blame for many of the hydrops cases happening) I really think that there are other benfits like better contant lens wear on a strengthened cornea is on the cards!!:)

All the Best



-- Edited by QuintriX at 01:19, 2005-09-12

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