CYP39A1 Gene Confers Cholesterol Homeostasis Against Exfoliation Syndrome & Glaucoma

Article: Scientists find gene mutation linked to exfoliation syndrome, most common cause of glaucoma
Source: Agency for Science, Technology and Research (Singapore), via ScienceDaily
Published: May 4, 2021

Lens with exfoliative material deposits

Singapore scientists conducted a genome-wide association study of exfoliation syndrome involving more than 20,000 participants from 14 countries across Asia, Europe, and Africa. Characterized by abnormal proteins in the anterior chamber of the eye, exfoliation syndrome is a major cause of glaucoma as these proteins accumulate in the trabecular meshwork and obstruct the normal flow of aqueous, leading to elevated intraocular pressure and subsequent optic nerve damage, i.e., glaucoma. According to the researchers, although exfoliation syndrome is the most common cause of glaucoma, little is known about the origins of the exfoliative material and the pathology of the disease. The research team identified genetic mutations in the CYP39A1 gene as being strongly associated with increased risk of exfoliation syndrome. People with exfoliation syndrome are twice as likely to carry damaging mutations to this gene. The CYP39A1 gene in particular encodes for the processing of cholesterol, which in turn is a major component of cell membranes. The researchers found that the epithelial cells of the ciliary body, responsible for producing aqueous humor as well as provide a barrier between the blood and the aqueous, were most affected by mutations in the CYP39A1 gene. When the blood-aqueous barrier is compromised, proteins from the blood can leak into the anterior chamber and accumulate, notably, in the trabecular meshwork. The presence of normal CYP39A1 thus has a significant stabilizing effect on cholesterol homeostasis, resulting in an intact blood-aqueous barrier that prevents leakage of exfoliative material into the anterior chamber.

My rating of this study: ⭐⭐⭐⭐

Li Z, Wang Z, Lee MC, et al. "Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye." JAMA.  325(8):753-764. 23 February 2021. https://doi.org/10.1001/jama.2021.0507