Does aberrant phospholipid flip-flop underpin visual disorders?
Mutations in the ABCR gene are responsible for a number of visual disorders including Stargardt's disease (STGD). This disease is associated with loss of central vision, delayed dark adaptation and progressive loss of photoreceptor cells. Diagnosis of the disease is apparent through the presence of small yellow pigmentation in the retina. The genetic basis for the disease has been understood since the late 1990s yet there is no treatment yet available.
A key factor in the lack of progress towards therapeutic strategies is shortfall in biochemical understanding. The ABCR gene encodes the ABCA4 membrane protein. ABCA4 is a member of the ABC superfamily of membrane transporters; however it's precise function in photoreceptor cells remains a mystery. The protein is localised to the disk membranes within photoreceptor cells and a role in retinal regeneration is postulated. More specifically, the ABCA4 protein is hypothesised to mediate the transmembrane translocation of a retinal-PE conjugate. Continuing work in the Callaghan group aims to test this hypothesis directly using purified, reconstituted ABCA4. We have international collaborations associated with this research project that may shape future therapeutic strategies to restore vision in macular degenerative disease.
For further information read the following review:
- Pollock N.L., and Callaghan R. (2011) The Lipid Translocase, ABCA4: seeing is believing. FEBS Journal 278, 3204-3214