Our long-range goal is to understand the factors which influence and determine the morphology of photoreceptive outer segments of vertebrate retina. In particular, we ask: 1) What controls the diameter of outer segments? 2) What controls their shape, to yield rod-like or cone-like structures? 3) What controls the topology of membrane relationships in outer segments, so that photoreceptive disks are isolated from or remain connected to the plasmalemma? Our recent morphological studies of the disk margin of frog rod outer segments (ROS) have revealed a clustering of structures we term the terminal loop (TL)-complex, to emphasize their location along the highly curved perimeter of the disk. The TL complex appears to be composed of 2 identical halves, and we suggest that this complex basically represents a dimer of the TL protein described by Papermaster et al. When the structural features of the TL complex are superimposed upon the geometrical scheme of disk development described by Steinberg et al., a rather simple hypothesis emerges which can account for several important features of ROS morphology, namely the alignment of disk margins and incisures. Furthermore, it suggests a general mechanism which probably controls the progressive separation of disks from the plasma membrane, and provides a simple explanation to account for the topological relationships of disks in cone and rod outer segments. Against this background, we propose experiments to test and extend this hypothesis.
Our aims are: 1) Examine by electron microscopy the photoreceptors of a selected number of vertebrate species to determine if a TL complex is present in all ROSs as predicted, and in cone outer segments along homologous regions of the cone disk perimeter. Using in vitro retina incubations, examine the effect of antibodies to the TL protein on disk margin formation. 2) Further define the structure and function of the rigid calycal processes which surround the base of most outer segments. In particular, we will try to determine if the actin filaments within calycal processes are festooned, as in the stereocilia of hair cells in the cochlea. Our basic idea is that the calycal processes limit the diameter of outer segments and determine the basic pattern of incisure formation in ROSs. 3) Determine the average number and geometrical features of connections between TLs across incisures, and between TLs and the plasmalemma. Significance: An understanding of the structural relationships normally involved in the maintenance of photoreceptor morphology can be expected to help us understand the extensive alterations in morphology involved in a wide range of degenerative changes, vitamin deficiences, and experimental manipulations of the retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004922-08
Application #
3259565
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-07-01
Project End
1993-09-29
Budget Start
1991-09-30
Budget End
1993-09-29
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Corless, Joseph M (2012) Cone outer segments: a biophysical model of membrane dynamics, shape retention, and lamella formation. Biophys J 102:2697-705
Corless, J M; Worniallo, E; Schneider, T G (1995) Three-dimensional membrane crystals in amphibian cone outer segments: 2. Crystal type associated with the saddle point regions of cone disks. Exp Eye Res 61:335-49
Corless, J M; Worniallo, E; Fetter, R D (1994) Three-dimensional membrane crystals in amphibian cone outer segments. 1. Light-dependent crystal formation in frog retinas. J Struct Biol 113:64-86
Conrad, T J; Chandler, D B; Corless, J M et al. (1994) In vivo measurement of corneal angiogenesis with video data acquisition and computerized image analysis. Lab Invest 70:426-34
Corless, J M; Worniallo, E; Fetter, R D (1989) Modulation of disk margin structure during renewal of cone outer segments in the vertebrate retina. J Comp Neurol 287:531-44
Lamvik, M K; Davilla, S (1989) Calibration methods for quantitative image processing in electron microscopy. J Electron Microsc Tech 11:97-101
Corless, J M; Schneider, T G (1987) Patterns of interdisk connections within the lamellar domains of retinal rod outer segment disks: observations relevant to the axial propagation of incisures. Exp Eye Res 45:883-905
Fetter, R D; Corless, J M (1987) Morphological components associated with frog cone outer segment disc margins. Invest Ophthalmol Vis Sci 28:646-57
Corless, J M; Fetter, R D; Costello, M J (1987) Structural features of the terminal loop region of frog retinal rod outer segment disk membranes: I. Organization of lipid components. J Comp Neurol 257:1-8
Corless, J M; Fetter, R D (1987) Structural features of the terminal loop region of frog retinal rod outer segment disk membranes: III. Implications of the terminal loop complex for disk morphogenesis, membrane fusion, and cell surface interactions. J Comp Neurol 257:24-38

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