title: Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults.
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.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, NY, USA, sungpyo@hallym.or.kr.
authors.forename: Sung Pyo
authors.initials: SP
authors.lastname: Park
authors.forename: In Hwan
authors.initials: IH
authors.lastname: Hong
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.forename: Jason
authors.initials: J
authors.lastname: Horowitz
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: Stanley
authors.initials: S
authors.lastname: Chang
mesh_terms: D000328:Adult; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D064847:Multimodal Imaging; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D012160:Retina / Q000503:physiopathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014157:Transcription Factors / Q000235:genetics*; D014786:Vision Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005136:Eye Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D014157:Transcription Factors