Ophthalmology
Cambridge, Massachusetts, United States
Proper vision depends on a complex and successful relationship between the retinal pigment epithelium (RPE) and the light-sensing photoreceptors. RPE cells are responsible for phagocytosis of spent discs contained within the outer segments that regularly shed from the neighbouring photoreceptors. These discs are richly endowed with 11-cis retinal bound to G-protein coupled receptors (opsins) and long chain phospholipids, such as docosahexaenoic acid (DHA) that promote appropriate light perception. Light stimulates isomerization of 11-cis-retinal, bound to rhodopsin, to all-trans-retinal and initiates the phototransduction cascade in rods. The RPE cells contain proteins that replenish the 11-cis-retinal, which is ultimately transported back to photoreceptors to be incorporated into newly-synthesized outer segment discs. Genetic analysis has identified many of the key genes involved in this process known as the visual cycle. Mutations that compromise genes involved in the visual cycle can lead to blindness and vision problems in humans. Much less is known about phospholipid trafficking and signalling in photoreceptor and RPE cells. We have recently identified a seven transmembrane protein, adiponectin receptor 1, as a key molecular switch that controls uptake and retention of DHA in the retina. This receptor is required for normal vision and survival of photoreceptors in the mouse retina. Key questions remain to be addressed regarding the mechanisms by which this protein facilitates DHA trafficking in the eye. The ultimate goal of our research is to determine if AdipoR1 biology contributes to a normal healthy retina and if modulation of this pathway is beneficial in diseases that compromise vision in humans.
Selected Publications
Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival
Rice DS, Calandia JM, Gordon WC, Jun B, Zhou Y, Gelfman CM, Li S, Jin M, Knott EJ, Chang B, Abuin A, Issa T, Potter D, Platt KA, Bazan NG.
Nat Commun. 2015 Mar 4; 6:6228.
Excitatory superficial dorsal horn interneurons are functionally heterogeneous and required for the full behavioral expression of pain and itch.
Wang X, Zhang J, Eberhart D, Urban R, Meda K, Solorzano C, Yamanaka H, Rice D, Basbaum AI.
Neuron. 2013 Apr 24; 78(2):312-24.
Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal.
McNeill M, Mazerolle C, Bassett EA, Mears AJ, Rinquette R, Lagali P, Picketts DJ, Paes K, Rice D, Wallace VA.
Hum Mol Genet. 2013 Mar 1; 22(5):1005-16
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