Discovery Magazine

Photo Credit: N. Nesnas

Retinal Synthesis

Nasri Nesnas and his research group are collaborating with Professor Michael F. Brown of the University of Arizona on a project that is aimed at understanding the visual process in detail. Vitamin A derivatives, which are key molecules in the visual process, change conformation in the rhodopsin protein that they are bound to the retina of the eye. There are five different -CH3 (Methyl) groups in vitamin A that are important to this conformational change that leads to vision. 

Vitamin A is formed as a result of the breakdown of a molecule, nearly twice its size, knonwn as beta-carotene.  The latter, as the name suggests, is plentiful in vegetables such as carrots, and similarly colored fruits including mangoes.  Vitamin A, which has a linear shape, is then converted via the action of several enzymes and retinal binding proteins to its active form, referred to as 11-cis-retinal. The latter has the shape of the letter V. A protein in the retina, known as opsin, will recognize and incorporate 11-cis-retinal, to form a light-sensitive form called rhodopsin.  Upon Irradiation with light, the V-shaped 11-cis-retinal in the rhodopsin will undergo a movement extending itself to its linear shape (from V --> /) causing the rhodopsin protein to change its shape accordingly (since it is housing it). The latter change in the shape of rhodopsin will trigger other proteins to be activated, ultimately leading to an electrical impulse passing through the optic nerve.  

We aim to study the movement of this vitamin A molecule within its binding pocket by replacing the -CH3 units with -CD3 in our vitamin A derivatives. The molecular design and construction of these vitamin A derviatives will take place at Florida Institute of Technology. The modified vitamin A derivatives will be shipped to Professor Brown's lab for their evaluation in the rhodopsin protein using advanced solid-state NMR techniques. 

We aim to understand the visual process in sufficient detail to help explain some visual malfunctions and long-term damage, most notoriously, Age-related Macular Degeneration (AMD).