This research is directed at a more precise understanding of photoreceptor membrane turnover. The significance of the work derives from the frequent pathological finding of injury to photoreceptors in hereditary and nutritional diseases, retinal detachment and drug studies which suggest that photoreceptor metabolism is in a delicate balance. One aspect of this is the extensive turnover of photosensitive membrane on which photoreceptor function depends. The anatomical polarity of the photoreceptor makes it possible to define a series of discrete """"""""subprocesses"""""""" or events which lead to turnover. Although these can be described operationally, the molecular-cellular mechanisms underlying them are poorly defined. This is a proposal to use high-resolution electron microscopic and fluorescence microscopic techniques coupled with specific ligands in an experimental attempt to analyze specific aspects of turnover. Special attention will be focused on the mechanism of visual pigment delivery to forming discs, the relationship of photosensitive membrane to cytoskeletal structures of the ciliary axoneme and the mechanisms involved in photosensitive membrane detachment and phagocytosis by pigment epithelial cells. Improved insight into these aspects of turnover may lead to a better understanding of pathological processes in photoreceptor degeneration.
| Lewis, Tylor R; Kundinger, Sean R; Link, Brian A et al. (2018) Kif17 phosphorylation regulates photoreceptor outer segment turnover. BMC Cell Biol 19:25 |
| Lewis, Tylor R; Zareba, Mariusz; Link, Brian A et al. (2018) Cone myoid elongation involves unidirectional microtubule movement mediated by dynein-1. Mol Biol Cell 29:180-190 |
| Lewis, Tylor R; Kundinger, Sean R; Pavlovich, Amira L et al. (2017) Cos2/Kif7 and Osm-3/Kif17 regulate onset of outer segment development in zebrafish photoreceptors through distinct mechanisms. Dev Biol 425:176-190 |
| Collery, Ross F; Volberding, Peter J; Bostrom, Jonathan R et al. (2016) Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages. Invest Ophthalmol Vis Sci 57:6805-6814 |
| Besharse, Joseph C; McMahon, Douglas G (2016) The Retina and Other Light-sensitive Ocular Clocks. J Biol Rhythms 31:223-43 |
| Miesfeld, Joel B; Gestri, Gaia; Clark, Brian S et al. (2015) Yap and Taz regulate retinal pigment epithelial cell fate. Development 142:3021-32 |
| Fogerty, Joseph; Besharse, Joseph C (2014) Subretinal infiltration of monocyte derived cells and complement misregulation in mice with AMD-like pathology. Adv Exp Med Biol 801:355-63 |
| Bader, Jason R; Kusik, Brandon W; Besharse, Joseph C (2012) Analysis of KIF17 distal tip trafficking in zebrafish cone photoreceptors. Vision Res 75:37-43 |
| Wong-Riley, Margaret T T; Besharse, Joseph C (2012) The kinesin superfamily protein KIF17: one protein with many functions. Biomol Concepts 3:267-282 |
| Malicki, Jarema; Besharse, Joseph C (2012) Kinesin-2 family motors in the unusual photoreceptor cilium. Vision Res 75:33-6 |
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