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Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults

  • Retinal Disorders
  • Published:
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Abstract

Background

Enhanced S-cone syndrome is an orphan disease caused by mutations in the NR2E3 gene which result in an increased number of S-cones overpopulating the retina. Although the characteristic onset of enhanced S-cone syndrome can be well-documented by current ophthalmic imaging modalities, techniques such as spectral-domain optical coherence tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) fail to provide sufficient details regarding the microstructure of photoreceptors in retinal diseases. Adaptive optics (AO) provides a unique opportunity to analyze the effects of genetic mutations on photoreceptors by compensating aberrations of human eyes.

Methods

Three eyes of three young adults with enhanced S-cone syndrome were studied by clinical examination, genetic screening, fundus autofluorescence (FAF) imaging, SD-OCT, and electroretinography (ERG). Cone mosaic imaging was accomplished by an AO-SLO equipped with a dual crystal on silicon spatial light modulator. Qualitative image analyses and genetic findings were investigated in each patient.

Results

The diagnosis of patients was confirmed by ERG finding. Genetic screening confirmed the presence of two disease-causing mutations in the NR2E3 gene in each study patient, as well as identified a novel mutation (202 A > G, S68G). Fundus photograph, FAF, and SD-OCT found rosette-like lesion within the mid-periphery along the vascular arcades of the retina. In all AO-SLO images of patients, sparse distribution and asymmetric size of cone mosaic pattern were found within central retina. There were regions of dark space between groups of photoreceptors, distinguishable from shadowing and artifacts.

Conclusions

AO-SLO provided an in-depth window into the retina of live enhanced S-cone syndrome patients beyond the ability of other current imaging modalities. Dark lesions within the central retina in each patient contain structurally dysfunctional cones which account for retinal mosaic disorganization, and may predispose affected areas to other abnormalities such as rosette lesions. AO-SLO can be an efficient diagnostic tool in clinics for examining cellular-level pathologies in various retinal dystrophies.

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Acknowledgement

Publication of this article was supported by multiple grants. These included the following: a Core Support for Vision Research grant (P30EY019007: SHT, RA) and National Eye Institute of The National Institutes of Health (Bethesda, MD, USA) grants (EY018213:SHT, EY019861: RA, SHT). Funds were also received from the Foundation Fighting Blindness (Owings Mills, MD, USA), as were unrestricted funds from Research to Prevent Blindness Inc, (New York, NY, USA). Dr. Tsang is a fellow of the Burroughs–Wellcome Program in Biomedical Sciences, and has been supported by the following grants: the Bernard Becker Association of University Professors in Ophthalmology Research to Prevent Blindness Award, the Foundation Fighting Blindness, Dennis W. Jahnigen Award of the American Geriatrics Society, Joel Hoffman Scholarship, and the Crowley Family Fund and Barbara & Donald Jonas Family Funds. The authors have no financial support or conflicts of interest from the materials or methods used in this investigation. Individual author contributions: Design and conduct of study (SPP, IHH, SHT); management, analysis, and interpretation of data (SPP, IHH, WL, SY, SHT); and preparation, review and/or approval of manuscript (SPP, WL, SC, RA, JH, SHT). The authors thank Canon Inc. (Tokyo, Japan) for their technical support with the AO-SLO system, and Elena N. Bukanova for technical support and contributions with genetic analyses. Further gratitude is extended to Drs. Lawrence Yannuzzi and Irene Barbazetto for patient referral.

Financial disclosure

The authors indicated no financial support or conflicts of interest.

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Authors and Affiliations

  1. Department of Ophthalmology, Columbia University, New York, NY, USA

    Sung Pyo Park, Stephen H. Tsang, Winston Lee, Jason Horowitz, Rando Allikmets & Stanley Chang

  2. Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Seoul, South Korea

    Sung Pyo Park & In Hwan Hong

  3. Department of Pathology & Cell Biology, Columbia University, New York, NY, USA

    Stephen H. Tsang & Rando Allikmets

  4. Rotterdam Eye Hospital, Rotterdam, Netherlands

    Suzanne Yzer

  5. Departments of Ophthalmology, Pathology and Cell Biology, Edward S. Harkness Eye Institute, Columbia University, 635 west 165th street, New York, NY, 10032, USA

    Stephen H. Tsang

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  1. Sung Pyo Park
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Correspondence to Stephen H. Tsang.

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Park, S.P., Hong, I.H., Tsang, S.H. et al. Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults. Graefes Arch Clin Exp Ophthalmol 251, 2299–2309 (2013). https://doi.org/10.1007/s00417-013-2296-5

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  • DOI: https://doi.org/10.1007/s00417-013-2296-5

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