VISUAL CYCLE

An imperfect recycling system

Plant 1 The retina is the thin membrane located at the back of the eye. It contains millions of photoreceptors used for vision, and plays a similar role as the light sensitive film at the back of a camera. These specialized receptors cover the retina and are responsible for black and white (rods) and for colored vision (cones). Vitamin A, which can be found on the tip of the rods, is the key to vision. Its exact role was explicited by George Wald and resulted in a Nobel Prize of 1967.

Vitamin A and several of its derivatives and precursors (such as beta-carotene), originate from certain types of food: eggs, milk, other dairy products contain vitamin A and green leafy vegetables, carrots, etc. contain beta-carotene. After vitamin A is transported into the retina, it is struck by light and its geometrical shape changes, acting like an electrical switch which enables the delivery of an electric signal to the brain. This signals the presence of light to the brain.

After vitamin A has changed its shape, it becomes insensitive to light and needs to be reactivated by specialized cells, the retinal pigmented epithelium (RPE). The geometric switch of vitamin A as well as its recycling by the RPE is called the "visual cycle". Unfortunately, the visual cycle is imperfect and some vitamin A molecules escape the "recycling system". These vitamin A can then bind to other vitamin A and create toxic molecules called A2E. A2E is then absorbed and stored in the RPE cells where they are considered to be responsible for the formation of another toxic compounds named lipofuscin.

With age, accumulation of lipofuscin leads to toxic chemical reactions, to degeneration of the RPE and to macular degeneration in certain patients. Stargardt's disease patients present a defective gene which prevents proper transport of vitamin A back into the RPE, resulting in faster accumulation of A2E and lipofuscin. This is why Stargardt's disease is also called "juvenile macular degeneration" and has an earlier onset of symptoms.

Visual cycle imperfections lead to A2E formation and to macular degeneration. Alkeus Pharmaceuticals is developing compounds that can help perfect this cycle, prevent the formation of toxic A2E and lipofuscin pigments and potentially slow down vision loss in dry-AMD and Stargardt's disease.