Retinal diseases platform

Biophytis has demonstrated that MACUNEOS protects the cells of the retina from the phototoxic effects of A2E in the presence of blue light (oxidative stress), reduces the accumulation of this phototoxic molecule in the animal models and thus slows down the retinal degeneration process, while maintaining the electrical activity of the retina (measured by electroretinography).

THE OXIDATIVE STRESS CAUSED BY A2E LEADS TO RETINAL CELL DEATH

Photoreceptors contain a visual pigment that absorbs some of the spectrum’s radiation, and it is this absorption of photons that is at the origin of the nerve messages they emit. Each visual pigment molecule consists of a protein called opsin and a non-protein molecule : retinal. Under the effect of light, the retinal is isomerised and detaches from the opsin. This return to its original form, which is essential to its activity, brings into play a sequence of reactions for which photoreceptors and the retinal pigment epithelium (RPE) are jointly responsible.

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This protection mechanism does however have a downside when, following a malfunction (associated with age or genetic defects), a molecule called A2E accumulates in large quantities in the cells of the RPE. In fact, in the presence of (blue) light and oxygen, A2E oxidises some or all of its double bonds and the molecules thus formed react with various cellular constituents, thereby disrupting the activity of the RPE and, in particular, its activity involving the digestion of fragments of photoreceptors. Because of this, the RPE cells accumulate the waste products, leading to a malfunction of the metabolism and of the various signalling pathways, which in turn leads to the death of retina cells.

Positive results of a potentially new protective pathway

Engaging PPAR nuclear receptors may protect the retina from oxidative stress and lead to many positive outcomes that collectively limit retinal degeneration.

PPARα along with PPARβ/δ promote retinal health by turning on anti-inflammatory and anti-oxidant genes and turning off pro-inflammatory genes. PPARβ/δ also decreases VEGF production, decreases cellular death, and stops free radical production to promote retinal health.

Studies conducted by Biophytis make it possible to specify that Macuneos binds to PPARγ, but does not seem to activate it, while it also interacts with PPARα and PPARβ/δ. The photoprotective effects of Macuneos are also reproduced by PPARα and PPARβ/δ agonists and inhibited by antagonists of the latter.

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Improved survival of RPE cells under blue light stress

Macuneos significantly protects RPE cells exposed to blue light and A2E, and more significantly than those compounds (lutein and zeaxanthin) where the AREDS studies have shown that their deficiency was linked to a high risk of developing dry AMD.

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Survival of RPE cells achieved by Macuneos in different concentrations
Comparison with lutein and zeaxanthin at the same concentrations

Improved functional protection of the retina

Macuneos provides significant protection at the structural level (number of layers of photoreceptors) and this results in an improvement in the function of the retina (electroretinogram). It is also more effective than the reference molecule (PBN) in blue light damage tests.

Photoreceptor layers

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Electroretinogram – A-wave

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Number of layers of photoreceptors and ERG (A waves) in the animal model for AMD
(Blue Light rat model with intraperitoneal injections).