Structural and molecular bases of rod photoreceptor morphogenesis and disease

• Published in: Progress in retinal and eye research Vol. 55; pp. 32 - 51
• Main Authors: Wensel, Theodore G., Zhang, Zhixian, Anastassov, Ivan A., Gilliam, Jared C., He, Feng, Schmid, Michael F., Robichaux, Michael A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2016
• Subjects: Ciliopathies; Cryo-electron tomography; Cryoelectron Microscopy - methods; Disease mechanisms; Humans; Membrane Proteins - metabolism; Morphogenesis; Photoreceptor; Retinal degeneration; Retinal Diseases - diagnosis; Retinal Diseases - metabolism; Retinal imaging; Retinal Rod Photoreceptor Cells - metabolism; Retinal Rod Photoreceptor Cells - ultrastructure; Disease mechanisms; STED; Photoreceptor; miniSOG; Ciliopathies; Cryo-electron tomography; SNAP tag; STORM; Cryo-ET; BBS; SIM; UPR; PALM; TPR; Retinal degeneration; SEM; BBSome; TEM; Retinal imaging; RP; ADRP
• ISSN: 1350-9462; 1873-1635
• DOI: 10.1016/j.preteyeres.2016.06.002

The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural features of the rod and the metabolic processes required for highly amplified light detection seem to have rendered the rod especially sensitive to structural and metabolic defects, so that a large number of gene defects are primarily associated with rod cell death and give rise to blinding retinal dystrophies. The structures of the rod, especially those of the sensory cilium known as the outer segment, have been the subject of structural, biochemical, and genetic analysis for many years, but the molecular bases for rod morphogenesis and for cell death in rod dystrophies are still poorly understood. Recent developments in imaging technology, such as cryo-electron tomography and super-resolution fluorescence microscopy, in gene sequencing technology, and in gene editing technology are rapidly leading to new breakthroughs in our understanding of these questions. A summary is presented of our current understanding of selected aspects of these questions, highlighting areas of uncertainty and contention as well as recent discoveries that provide new insights. Examples of structural data from emerging imaging technologies are presented. •Review of historical and most recent structural studies of vertebrate rod cells.•Current state of understanding of basal disk structure and morphogenesis.•Cryo-electron tomography and superresolution microscopy of rods.•Advances in understanding of cilium-associated structures.•Current understanding and uncertainties in mechanisms of rod dystrophies.