BLOG: What a tiny piece of tissue teaches us about ancestry
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Glaucoma is about many things, but most relate to a tiny piece of tissue called the trabecular meshwork, the exit filter for aqueous humor leaving the eye.
A healthy trabecular meshwork (TM) permits balanced inflows and outflows and prevents optic nerve-wrecking rises in IOP.
Sitting out of sight between the cornea and the peripheral iris, the TM weighs maybe 50 mg and is thinner and more fragile than a wet coffee filter. Iris color loosely influences the color of the TM, but it otherwise looks much the same across populations. Its permeability determines IOP and the difference between sight and blindness.
For its unimpressive appearance, one would expect the eye’s outflow pathway to be much the same in all of us, with glaucoma being essentially the same disease, regardless of ancestry. In some populations such as Scandinavians, individuals from the Middle East and some from South Africa, however, the TM becomes clogged with PAS-positive pseudoexfoliation material manufactured by the TM itself, along with other cells. In some Asian populations, the TM is crowded by a forward-displaced lens-iris diaphragm, raising baseline IOP and the specter of narrow-angle glaucoma. In many populations, the aging process can result in loss of the vital function of the TM cells, leaving acellular collagenous beams that ultimately collapse. This transformation leads to reduced outflow capacitance and more aggressive glaucoma than in others.
These ideas are well known to us because we ophthalmologists are privileged with access to look microscopically at the organ we treat and see the pathophysiology happening before us. In other areas of study, even in the eye, we lack the strong signals that the TM has been sending us for decades.
Diseases of the liver, kidneys, heart and brain don’t come with signposts indicating these differences across populations, yet the implications are just as important as blindness vs. sight. As scientists, we only get answers when we ask questions, and in so many medical studies, we have failed to ask whether ancestry matters by including diverse study participants who represent the population at large.
To conclude without proof that differences in diseases between populations are attributable only to differences in education, access to care and other social inequities is missing a major opportunity. As medical researchers, we need to be more inclusive in our clinical trial recruitment. (After all, without the intentional diversification of the Ocular Hypertension Treatment Study, central corneal thickness as a risk factor would not have emerged as a finding.) We need to make a priority of understanding the conditions we treat from the perspective of all populations because the differences are great. Just ask the trabecular meshwork.
Hovanesian would like to acknowledge Eve Higginbotham, MD, for her assistance in editing this post.
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