When I started my PhD, I had every intention of finding a cure for cataracts – not after a few decades of research, but for the duration of my thesis. So much for my enthusiasm and my naivety at the time… But a few decades later, finally, this dream seems to be getting closer.
Cataracts result from the accumulation in the lens of fragmented proteins which will gradually cloud it. This clumping of material impairs the proper transmission of light to the retina, giving that characteristic hazy appearance to the eye. But, above all, it causes a decrease in vision which is more blurred. It is the cause of approximately 43% of blindness cases.
Surgery to remove the cloudy lens and replace it with an artificial equivalent is so far the only treatment available. Around 10 million cataract surgeries are performed each year worldwide (and 450,000 in France, where it is the leading cause of surgery, editor’s note).
Now well mastered, this surgery can change your life… But who wouldn’t prefer to avoid an intervention on the eye if a less invasive treatment were available? Hence our proposal: administer simple eye drops based on sterols, substances of the family of fats that exist in nature.
Coming into the game of eye drops
The sterol compound we identified had been tested before, but not for its effect on the optical quality of the lens. Yet this is a fundamental property of the eye for light to travel unhindered to the retina, and therefore to maintain vision.
Investigations carried out in 2015 on a panel of molecules, including this sterol compound, showed that it was capable of partially restoring the solubility of proteins both in the lenses of aged living mice and in human lenses placed in vitro, in Petri dishes. Resulting in improved lens transparency in aged mice
However, a subsequent study in 2019 could not confirm that this compound could indeed reverse protein accumulation in rat and human samples, or lens clouding in aged rats with cataracts. However, the sterol compound had not been tested on whole, intact human lenses.
And, above all, its effect on the optical quality of the lens (in this case the optical property of its refractive index) had not been measured.
To find out for sure, my colleagues and I recently conducted a new study on 26 mice with cataracts. She well showed promising and dramatic effects on cataracts after her application of the selected sterol compound on their eyes.
When the compound was applied to just one of their diseased eyes (to allow comparison), we found that lens opacity was reduced in 46% of cases. In addition, 61% of the treated lenses showed an improvement in the gradient of their refractive index. This gradient is an important measure of optical density, and an essential element of perceived image quality.
However, beneficial effects were not seen in all mice. This suggests that this type of treatment may not apply to all cataracts (there are several types, depending on their location, whether it is related to age, shock, etc.).
Assess the effect on optical quality
To arrive at this observation, it was necessary to have the means to finely evaluate the evolution of the optical quality of the lens. For this, I spent years developing suitable measurement methods. For more than ten years, I have been focusing on lens optics using the SPring-8 synchrotron in Japan – one of the most powerful in the world. This particle accelerator produces powerful X-rays, making it possible to measure the properties of the eye with unprecedented precision.
The application of X-ray measurements has been the key to our latest discoveries. Moreover, we work on whole lenses, so that the distribution of problematic proteins is not disturbed there – which is fundamental to reliably study its optical properties.
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It is this technology that has allowed me and my colleagues to accurately characterize the refractive index gradient in young, clear lenses as well as their avatars present in older, affected eyes. by cataract. As we said, this gradient is important for the quality of the image because it allows a better ability to focus. When the cataract develops, fragmented proteins accumulate in the lens, which disrupts this gradient… and therefore vision.
A track under development
The link between the optical function of the lens and the solubility of proteins and their propensity to agglomerate must continue to be investigated further. This is necessary to confirm that it is indeed possible to reverse the process of cataract formation, and thus to restore the transparency of a clouded lens.
Scientists have long believed that the buildup of the main structural cataract proteins – the lens – is irreversible. Therefore, cataract treatment could, at best, only halt or slow its progression.
If this is not the case, as our results suggest, and protein aggregation is indeed reversible, this opens up a whole host of possibilities for future treatments…
Not only could cataract be prevented by avoiding certain known causes, such as poor diet, smoking and certain medications, such as steroids, but it might be possible to develop drugs to prevent the progression of the disease. Others could be considered to reverse the process of cataract formation and restore clarity to a clouded lens.
Future research must include investigations of all the proteins of the lens: the main structural proteins of the lens (crystalline, membrane proteins ensuring the transport of water…) in tandem with studies of the optical function.
We continue to study lens optics in all its aspects and at all ages, from the early stages of embryonic development to adulthood. Our objective ? Know how these results, these observations can be related to changes in the proteins that constitute this organic lens.
Much more research than ours is of course still needed, but our latest findings have shown that non-surgical cataract treatment is possible. Better, it may be closer than we think…
The original version of this article was été published on The conversation, a news site à dédié to the sharing of ideas between academic experts and the general public.