Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

Emily J. Patterson; Melissa Wilk; Christopher S. Langlo; Melissa Kasilian; Michael Ring; Robert B. Hufnagel; Adam M Dubis; James J. Tee; Angelos Kalitzeos; Jessica C. Gardner; Zubair M Ahmed; Robert A. Sisk; Michael Larsen; Stacy Sjoberg; Thomas B. Connor; Alfredo Dubra; Jay Neitz; Alison J. Hardcastle; Maureen Neitz; Michel Michaelides; Joseph Carroll

doi:10.1167/iovs.16-19608

Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

Emily J. Patterson, Melissa Wilk, Christopher S. Langlo, Melissa Kasilian, Michael Ring, Robert B. Hufnagel, Adam M Dubis, James J. Tee, Angelos Kalitzeos, Jessica C. Gardner, Zubair M Ahmed, Robert A. Sisk, Michael Larsen, Stacy Sjoberg, Thomas B. Connor, Alfredo Dubra, Jay Neitz, Alison J. Hardcastle, Maureen Neitz, Michel MichaelidesJoseph Carroll^*

^*Corresponding author for this work

Developmental biology - endoderm and pancreas development Lab

12 Citations (Scopus)

63 Downloads (Pure)

Abstract

PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction.

METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family.

RESULTS. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/ M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

Original language	English
Journal	Investigative Ophthalmology and Visual Science
Volume	57
Issue number	8
Pages (from-to)	3853-3863
Number of pages	11
ISSN	0146-0404
DOIs	https://doi.org/10.1167/iovs.16-19608
Publication status	Published - 2016

Keywords

Adaptive optics
Color vision
Dichromacy
Myopia
Opsin

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10.1167/iovs.16-19608Licence: CC BY-NC-ND

Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision DeficiencyFinal published version, 1.28 MBLicence: CC BY-NC-ND

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Patterson, E. J., Wilk, M., Langlo, C. S., Kasilian, M., Ring, M., Hufnagel, R. B., Dubis, A. M., Tee, J. J., Kalitzeos, A., Gardner, J. C., Ahmed, Z. M., Sisk, R. A., Larsen, M., Sjoberg, S., Connor, T. B., Dubra, A., Neitz, J., Hardcastle, A. J., Neitz, M., ... Carroll, J. (2016). Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency. Investigative Ophthalmology and Visual Science, 57(8), 3853-3863. https://doi.org/10.1167/iovs.16-19608

Patterson, EJ, Wilk, M, Langlo, CS, Kasilian, M, Ring, M, Hufnagel, RB, Dubis, AM, Tee, JJ, Kalitzeos, A, Gardner, JC, Ahmed, ZM, Sisk, RA, Larsen, M, Sjoberg, S, Connor, TB, Dubra, A, Neitz, J, Hardcastle, AJ, Neitz, M, Michaelides, M & Carroll, J 2016, 'Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency', Investigative Ophthalmology and Visual Science, vol. 57, no. 8, pp. 3853-3863. https://doi.org/10.1167/iovs.16-19608

@article{71ae6622244544a2bc4a397819df5ac0,

title = "Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency",

abstract = "PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. RESULTS. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/ M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.",

keywords = "Adaptive optics, Color vision, Dichromacy, Myopia, Opsin",

author = "Patterson, {Emily J.} and Melissa Wilk and Langlo, {Christopher S.} and Melissa Kasilian and Michael Ring and Hufnagel, {Robert B.} and Dubis, {Adam M} and Tee, {James J.} and Angelos Kalitzeos and Gardner, {Jessica C.} and Ahmed, {Zubair M} and Sisk, {Robert A.} and Michael Larsen and Stacy Sjoberg and Connor, {Thomas B.} and Alfredo Dubra and Jay Neitz and Hardcastle, {Alison J.} and Maureen Neitz and Michel Michaelides and Joseph Carroll",

year = "2016",

doi = "10.1167/iovs.16-19608",

language = "English",

volume = "57",

pages = "3853--3863",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "8",

}

TY - JOUR

T1 - Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

AU - Patterson, Emily J.

AU - Wilk, Melissa

AU - Langlo, Christopher S.

AU - Kasilian, Melissa

AU - Ring, Michael

AU - Hufnagel, Robert B.

AU - Dubis, Adam M

AU - Tee, James J.

AU - Kalitzeos, Angelos

AU - Gardner, Jessica C.

AU - Ahmed, Zubair M

AU - Sisk, Robert A.

AU - Larsen, Michael

AU - Sjoberg, Stacy

AU - Connor, Thomas B.

AU - Dubra, Alfredo

AU - Neitz, Jay

AU - Hardcastle, Alison J.

AU - Neitz, Maureen

AU - Michaelides, Michel

AU - Carroll, Joseph

PY - 2016

Y1 - 2016

N2 - PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. RESULTS. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/ M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

AB - PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. RESULTS. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/ M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

KW - Adaptive optics

KW - Color vision

KW - Dichromacy

KW - Myopia

KW - Opsin

U2 - 10.1167/iovs.16-19608

DO - 10.1167/iovs.16-19608

M3 - Journal article

C2 - 27447086

AN - SCOPUS:84992348116

SN - 0146-0404

VL - 57

SP - 3853

EP - 3863

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 8

ER -

Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

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Keywords

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