Thursday, November 29, 2007

1.7 What about genes?

Even now, we are still blitzed by the media as far as "gene of the week", yet so far no "breaking news" on the myopia front. No, it is not as if no one is interested. Quite the contrary. It is just that nobody knows if there is only one myopia causative gene or an assortment of genes working in concert or in tandem, and what the gene products might be. Or, horrors, maybe there is no such thing as a school myopia causative gene at all. Whatever it is, it is a daunting fishing expedition involving several modes:

Matter-of-fact mode: "Our work confirms a previously reported [refractive error] linkage region on 22q and identifies 2 novel regions of linkage on 1q and 7p. Further, genetic research is needed to finemap this trait to identify the causative gene" (Beaver Dam Eye Study).
Exclusion mode: For example, one report points out that neither PAX6 nor SOX2 should be a priority in the search for genetic modifiers of myopia, and in another: sequence variants of the TGF-beta1 gene are not associated with high myopia.
Inclusion mode: For example, in an Australian study, axial length is found to be highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.
Humpty-Dumpty mode: hereditary high myopia loci (MYP12) may contribute to all degrees of myopia.
And to make it even more challenging or muddy-the-water mode: a study finds that an X-linked high myopia locus is mapped to Xq25-q27.2 which overlaps with that of MYP13 but is outside MYP1.

These are just a small sample of reports published in 2007, from all over the world. You can go to and enter keywords: "gene and myopia" to find the above and more. Notice, however, that they are not genetics of school myopia per se. The emphasis is still necessarily on families with high myopia which is usually not morphometrically defined. So we don't know if the eyes contain a posterior staphyloma component.

Ideally of course, if a causative gene can be identified, then we are talking gene therapy to decrease the risk of developing myopia. The other side of the coin is, what are the environmental factors that initiate or contribute to myopia gene expression. Then modifying these factors is probably as effective as the genetic approach.

Ah, now we are back to nature or nurture.

In a paper published in 2005, a mutation in MFRP gene is linked to nanophthalmos (dwarf eye) which is an under-developed, very hyperopic eye. And the missing MFRP protein has been proposed to regulate the eye growth. Very intriguing finding indeed.

You know what I think? Since myopization involves expansion of the eye globe implying a re-structuring of collagen fibers in the sclera. Then it is probably one of the MMPs that is asked to loosen the inter-fiber bonds - through the mediation of the MFRP protein. By concentrating on this one aspect, perhaps this MMP can be isolated and an inhibitor developed. Nothing fancy, just old-fashioned biochemistry. Much like using the statins to inhibit HMG-CoA reductase and stop cholesterol synthesis all together.

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