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closeClarification on cataract genesis in man.
Posted by cement_head on 23 Feb 2012 at 14:02 GMT
I have to disagree with the second sentence of the "Abstract" and the first sentence of the "Conclusions". Human beings are homoeothermic, that is, they maintain a body temperature of approximately 37oC. While temperature varies with location (e.g. the tips of fingers on a cold day are cooler than the body core), I think it is both inaccurate and incorrect to state that thermal fluctuations occur to elevate the lens temperature to above 45oC, and that this is the primary cause of human lens cataract.
The primary cause of human lens cataract is still debated, but it appears from the literature that it is largely due to the damage incurred by (and to) beta and gamma crystallins that overwhelm the alpha crystallin's ability to mitigate beta-gamma (as well as their own) aggregation. Beta and gamma crystallins appear to be extremely sensitive to damage (based on large numbers of reports on congenital cataracts and analysis of human cataractous lenses by 2D PAGE). It is also interesting to note that beta crystallins undergo tremendous amounts of PTMs and truncations that may lead to cataracts. This is in contrast to alpha crystallin, which appears to be quite a "hardy" molecule. No doubt when the in vivo damage to alpha crystallin becomes acute this would lead to cataracts, but the way the statement in this paper is phrased leads one to think that humans have a large phase transition at 45oC, which I am unaware as being physiologically possible.
RE: Clarification on cataract genesis in man.
gmaulucci replied to cement_head on 24 Feb 2012 at 13:46 GMT
Please see the discussion at the end, and the related reference, to get clarifications
Lens crystallin is particularly recessive to deleterious effects from elecromagnetic radiations that are known to be a potential risk factor for cataract and other eyes diseases. Indeed, its aqueous content favors radiation absorption and the very weak vascularization makes difficult to stand fast temperature increases [39].
"In this context, the natural self-protective mechanism that we report preserves the lens from premature opacification throughout the lifespan of the organism [40], abruptly reducing the formation of aggregates in the lens fiber cells under hyperthermic conditions, such as those determined by extended exposure to microwaves or other electromagnetic radiation emitted by cell and cordless phones, wireless communications, monitors and even high voltage lines [41]–[45]."
Thanks
Giuseppe Maulucci
RE: RE: Clarification on cataract genesis in man.
cement_head replied to gmaulucci on 24 Feb 2012 at 19:25 GMT
Most of those papers you've cited are either theoretical or non-physiological. The only one that might be plausible states that the lens may increase +1.4oC, but again, this is no measured.
The problem with theory, is that theoretically, theory and practice are the same. Unless one can demonstrate (measure) that a human lens achieves +45oC for sustained periods of time, the argument that temperature increases are the primary cause of human lens cataract, I find that statement unsubstantiated.
This is not to say that I don't find this paper's work interesting and informative and valid. I do think that thermal denaturation is very instructive to understanding globular protein stability. However, I simply don't buy that temperature is the principal driver of cataracts in man. Perhaps the authors should consider modelling ectothermic vertebrate lenses, particularly from those animals that are those animals which are stenothermal, such as cold adapted animals. Then the argument that elevated temperature might be more appropriate, if, and only if those temperature are physiologically realistic (i.e. have been measured).
Regards
RE: RE: RE: Clarification on cataract genesis in man.
gmaulucci replied to cement_head on 13 Apr 2012 at 13:33 GMT
Dear reader
In the paper we stated that "The increase in light scattering in old and cataractous lenses can be ascribed to alterations in lens crystallins interactions due to age related post-translational modification of -crystallin [5]–[8]. The alterations are triggered by lens cells exposition to elevated temperatures or other stress factors like ions, that disrupt the liquid-like molecular order and promote the formation of large scattering particles [9], [10], following pathways that include both changes in the secondary structure and in the state of assembly". Therefore temperature, as other stresses (i.e. redox state, ions, pressure), is one of the possible mechanism that allow to modify the protein structure and eventually induce fast aggregation. This mechanism is widely adopted in literature and this is why it has been used in this paper.
Besides small deviations of body temperature from 37°C occur in mammals and may induce relevant damage(for example, during fever or hyperthermic treatment, the body can reach temperatures up to 42°C). In these cases, in some cells, heat shock response activates the transcription of many chaperone proteins (and among them alpha-B crystallin). Lens cells can't afford this kind of defense mechanism since they haven't the nucleus: in this case the protection mechanism described in the article would protect from aggregation. Of course 45°C is letal for the organism, but there are many suggestions in literature that show how the critical temperature is highly dependent on protein and ions concentration. Since in the lens cell concentration of alpha crystallin is about 300mg/ml (300 times larger than that used in this paper), we're performing experiments to verify this hypotesis.
Regards
the authors of the article