Eye drops designed to lower cholesterol may be able to prevent one of the most common forms of blindness in the aged, a new study led by Indian-origin scientist has found.
Targeting cholesterol metabolism in the eye might help prevent a severe form of age-related macular degeneration (AMD), according to indications in a mice study led by Rajendra Apte, a professor of ophthalmology and vision sciences at Washington University in St Louis.
Cholesterol build-up in arteries and veins, or atherosclerosis, occurs as a natural consequence of ageing.
Likewise, in AMD, cholesterol is known to accumulate in the eye, within deposits called drusen.
The study, published in Cell Metabolism, shows that large cells called macrophages appear to play a key role in clearing cholesterol from the eye, and that with ageing, these cells become less efficient at this task.
Eye drops containing a type of drug known to promote cholesterol release from macrophages, called a liver X receptor (LXR) agonist, helped restore macrophage function and prevent AMD progression in a mouse model.
AMD causes damage to the macula, a region of the retina responsible for central, high-resolution vision.
"This study points to a novel strategy for early intervention to prevent the progression of AMD to the severe neovascular form of the disease," said Grace Shen, a programme director at NIH's National Eye Institute.
A protein called ABCA1 is needed for macrophages to release cholesterol into the bloodstream. In these experiments on mice, Apte and his team found that in old macrophages, there is a decrease in the level of ABCA1 protein.
The researchers found a similar drop in ABCA1 levels in blood cells - the source of macrophages - in samples donated by older people (aged 67-87) vs younger ones (aged 25-34).
To investigate the link between these changes and blood vessel growth, the researchers first performed tests in cell culture. When grown in a dish with blood vessel cells, young macrophages efficiently stopped the cells from multiplying, but old macrophages did not. Deleting the ABCA1 gene in young macrophages caused them to behave like old macrophages.
Next, the researchers tried treating old macrophages with an LXR agonist, these drugs are known to enhance cholesterol transport from macrophages by turning on the ABCA1 gene. Exposure to the drug rejuvenated the old macrophages and enabled them to inhibit blood vessel cell growth.
Researchers also tested the LXR agonist in mice with an eye injury that produces abnormal blood vessel growth, similar to that seen in neovascular AMD. Eye drops of the drug significantly reduced this blood vessel growth when given several days before the injury.
