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M.S. Eckmiller; Elucidating the Mechanism of Cone Alignment . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2847.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the cytoskeleton in primate cone myoids and formulate a model for the mechanism of cone alignment, because disturbed alignment of macular cones could account for metamorphopsia in early age–related macular degeneration.
Transverse sections through the foveal center of Macaca fascicularis retinas were examined by electron microscopy. Detailed observations were made at the base of the cone inner segment myoid, where the bend occurs to adjust alignment. The findings were combined with physiological optics in a model for cone alignment.
The cytoplasm at the base of the cone myoid contained microfilaments and numerous microtubules, but no other distinctive organelles. Longitudinally oriented microtubules were distributed throughout the myoid base, with their centers often as close as 56 nm. Microtubules occupied ∼20% of the cross–sectional area at the base of the myoid, where an individual cone could have >1500 microtubules. Based on these findings, microtubules were incorporated into the following model for the cone alignment mechanism: 1) Sensory input is provided by white light that enters the pupil and is refracted in a wavelength () dependent manner so as to be dispersed to different retinal locations with different orientations. At the retinal location of a given (correctly aligned) cone, those light rays having the preferred orientation enter the cone aperture at the myoid base most effectively; these rays arrive at different locations within the cone aperture, producing a spatially distributed spectrum or "rainbow". Because of symmetry about the visual axis, for cones throughout the retina the rainbow is oriented in a radial direction (short s foveal, long s peripheral). Thus, individual microtubules at different radial positions of the cone aperture receive light rays that differ systematically in . Furthermore, for cones in the macula the rainbow will be modified due to filtering by macular pigment. 2) Integration of the sensory input received by all the microtubules at the myoid base indicates if the alignment direction of a cone needs to change; the spectral spread of the rainbow shows the magnitude and direction in which change is needed. 3) Motor output is accomplished by a dependent response of the microtubules that produces a coordinated bending at the base of the cone myoid.
These findings and this novel sensory–motor feedback mechanism for normal cone alignment may be clinically relevant. Because there is evidence that macular cones become misaligned before undergoing apoptosis in age–related macular degeneration, these results may be a first step towards devising a therapy that preserves macular cone alignment.
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