In honour of June being “Cataract Awareness Month”, here is some exciting news: a topically applied drug has presented very positive results for treating cataracts in a laboratory setting, bringing us one step closer to a non-surgical cataract cure!
In the study led by Professor Barbara Pierscionek, the administration of an oxysterol compound was tested to see if it affected the optics of mice lenses. Out of the 35 mouse subjects, 26 received a single drop of 2mM VP1-001 (an oxysterol) in the left eye three times per week for two weeks, and only vehicle in the right eye. The remaining nine mice were untreated controls for comparison. Slit-lamp biomicroscopy was used to analyze the lenses and apparent cataract grades. Furthermore, the researchers also analyzed the lenses’ gradient refractive index (GRIN) profiles with X-ray phase tomography based on X-ray Talbot interferometry with a synchrotron radiation source, which yields a more detailed three-dimensional GRIN.
As a result, a greater level of lens transparency was seen in the VP1-001 treated eyes when compared to the eyes left untreated. The oxysterol compound improved the refractive index profiles in 61% of lenses and reduced lens opacity in 46% of cases. These results imply that the protein disorganization responsible for the cataract-related degradation in vision could be restored, ultimately leading to improved vision. This is a marvel finding, as it shows a potential topical treatment for cataracts.
The global burden of Cataracts
Cataracts are responsible for vision loss or impairment in about 50% of the population over 70 years old. Millions of people worldwide have cataracts, and it is considered the primordial global cause of blindness. A cataract is defined as the loss of transparency of the intraocular crystalline lens. The alpha-crystallin protein, which is believed to allow the eye lens to be transparent and flexible, becomes prone to misfolding and clumping with aging. This ultimately leads to a loss of transparency, preventing light from travelling to the retina, thus negatively affecting vision.
A closer look at Oxysterol
An essential factor in lens transparency is water and its transport regulation by aquaporins. The most abundant aquaporin in the lens is aquaporin 0, whose water permeability is modified by the lipid composition of the cell membrane bilayer. Oxysterols are involved in cholesterol homeostasis, and side-chain oxysterols that are enzymatically produced can enhance membrane permeability. A working hypothesis in this study is that oxysterol VP1-001 may have interacted with aquaporin 0, altering membrane permeability and the protein to water ratio, contributing to the improvement in the GRIN profile.
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