Residual Cone Structure in Patients With X-Linked Cone Opsin Mutations. Invest Ophthalmol Vis Sci 2018 Aug 01;59(10):4238-4248
Date
08/22/2018Pubmed ID
30128495Pubmed Central ID
PMC6103386DOI
10.1167/iovs.18-24699Scopus ID
2-s2.0-85052696691 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
PURPOSE: To assess residual cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW opsin.
METHODS: Thirteen males had their OPN1LW/OPN1MW opsin genes characterized. The cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and cone density was measured across imaging sessions.
RESULTS: Ten subjects had an OPN1LW/OPN1MW "interchange" opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in cones expressing LIAVA and greatly reduced functional photopigment in cones expressing LVAVA. Despite disrupted cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce cones that are devoid of functional opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding cones and axial length.
CONCLUSIONS: Split-detection imaging revealed that the altered appearance of the cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore cone function. The relative fraction of waveguiding cones was highly variable across subjects, which appears to influence emmetropization in these subjects.
Author List
Patterson EJ, Kalitzeos A, Kasilian M, Gardner JC, Neitz J, Hardcastle AJ, Neitz M, Carroll J, Michaelides MAuthor
Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAxial Length, Eye
Color Vision Defects
Cone Opsins
Emmetropia
Exons
Genes, X-Linked
Humans
Male
Middle Aged
Mutation
Phenotype
Retina
Retinal Cone Photoreceptor Cells
Rod Opsins
