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BIOBOARD
Shining Light on the “Silent Thief”
Researchers from the Agency for Science, Technology and Research (A*STAR) and Singapore Eye Research Institiute (SERI) have discovered a genetic mutation linked to exfoliation syndrome, the most common cause of glaucoma.

Glaucoma is a blanket term for eye diseases characterised by the loss of retinal ganglion cells due to intraocular hypertension, or put simply, a build-up of pressure on our optic nerves. Estimated to plague 70 million individuals worldwide, glaucoma is one of the leading causes of visual morbidity and irreversible blindness for individuals above the age of 60. This eye condition is known to be painless and asymptomatic in nature, thus often remain undetected until it reaches a point of damage critical enough to cause total blindness. Its stealthy mode of degeneration is reflective of its appropriately infamous moniker – the silent thief of sight.

As a multi-factorial disease, the aetiology of glaucoma has remained shrouded in mystery, hence impeding advancements in treatment and prevention methods. That is, up until recently.

A ground-breaking association between genetic mutations and exfoliation syndrome was unearthed by a team of researchers from the Genome Institute of Singapore (GIS) and Bioprocessing Technology Institute (BTI) of the Agency for Science, Technology and Research's (A*STAR), as well as Singapore Eye Research Institute (SERI). Exfoliation syndrome, one of the primary causes of glaucoma, is a systematic disorder associated with the progressive accumulation of abnormal proteins in front of the eye which may result in permanent loss of vision.

In their cross-continental study involving more than 20,000 individuals from 14 different countries, the team observed that people suffering from exfoliation syndrome are twice as likely to carry mutated genes encoding for the CYP39A1 protein. Mutated CYP39A1 proteins were found to pose destructive effects on epithelial cells located in the front of the eyes, which are responsible for filtering blood supply to produce and maintain the aqueous humour – the clear fluid in our eyes to bathe and nourish eye cells.

In conjunction with this recent breakthrough, present literature attributes the development of exfoliation syndrome to disrupted cholesterol processing. Hence it is postulated that defective CYP39A1 proteins may be accountable to the detrimental effects on normal cholesterol processing.

With further analyses and collaboration with other scientists worldwide, unveiling the truths behind the origins of glaucoma is expected to shed more light on the mechanisms of the disease and illuminate the path to cure.

As rightfully pointed out by Professor David Friedman of Harvard University, this “exciting work” and those soon to follow suit have much potential in opening “new doors to novel therapeutics”. Only through better understanding of the disease can efforts be made to develop more targeted therapies and treatments such as “restoring defective CYP39A1 function and inhibiting the formation of exfoliation material in the eye,” as stated by Professor Patrick Tan, Executive Director of GIS.

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