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Dr. Carroll: Advances in Retinal Imaging of Achromatopsia
1. Advances in Retinal Imaging of Achromatopsia Joseph Carroll, PhD Departments of Ophthalmology, Biophysics, and Cell Biology, Neurobiology, & Anatomy Medical College of Wisconsin Achromatopsia Convention August 2, 2011
2. Acknowledgements Medical College of Wisconsin Kim Stepien, MD Alf Dubra, PhD JungtaeRha, PhD Robert Cooper Adam Dubis Brett Schroeder Phyllis Summerfelt Chicago Lighthouse/UIC Gerald Fishman, MD Mohamed Genead, MD University of Washington Jay Neitz, PhD Maureen Neitz, PhD $$$$ - NIH EY017607, EY001931, Research to Prevent Blindness, E. Matilda Ziegler Foundation for the Blind, Kirchgessner Foundation, Gene & Ruth Posner Foundation, RD & Linda Peters Foundation, Hope for Vision, Vision for Tomorrow Foundation, & Fight for Sight
3. Complex layered structure which is made up of different types of cells. Picture from Webvision: The Organization of the Retina and Visual System
7. In achromatopsia, we are interested in studying photoreceptor structure – as this is likely to be helpful in the translation of gene-based therapies to the condition. Two imaging techniques have emerged that allow us to directly assess photoreceptor structure in patients with achromatopsia and other retinal disorders…
12. Imaging the Rod and Cone Mosaic Dubra, Sulai, Norris, Cooper, Dubis, Williams, Carroll(2011)
13. With the ability to resolve the entire photoreceptor mosaic, we can quantify different aspects of the rod and cone mosaics… Dubra, Sulai, Norris, Cooper, Dubis, Williams, Carroll(2011)
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15. cone function improved in dog and mouse models of congenital achromatopsia (Komáromyet al., 2010; Alexander et al., 2007),
16. trichromatic color vision achieved in a primate model of human dichromacy (Mancuso et al., 2009)A better understanding of photoreceptor structure is needed in order to assess the therapeutic potential in human patients with AHCM & BCM.
21. Histology data varies: from suggesting normal peripheral cones (Larsen, 1921), reduced numbers throughout (Harrison et al., 1960; Glickstein & Heath, 1975), or normal numbers in the fovea (Falls et al., 1965).
28. Variation in cone structure within individual retina. Geneadet al. (2011)
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30. OCT reveals significant variation in the disruption of the IS/OS, and variable thinning of the ONL – suggesting variable degrees of photoreceptor loss.
31. Imaging with AO reveals significant cone structure in most patients, with some even retaining both an inner and outer segment to the cone. These cones are not functioning normally, but appear to be intact structurally, at least in part.
40. JC_0183 JC_0184 Curcio et al. (1991) 2,626 cones/mm2 4,116 cones/mm2 2,000 – 5,000 cones/mm2 S-Cone Free Zone - Data is consistent with the S-cone free zone being variable in size (Williams et al., 1981; de Monasterioet al., 1985; Norket al., 1990; Curcio et al., 1991). - Residual packing density of S-cones may contribute to phenotypic heterogeneity.
41. Peripheral BCM Mosaic Rods begin to appear. Large, bright S cones no longer visible, rather cones appear dark (inner segment). Fewer in number than AHCM.
