June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Comparison between human NR2E3-related disease and murine retinal characteristics identifies interspecies imaging correlates of key histological findings in rd7 mice
Author Affiliations & Notes
  • Alessandro Iannaccone
    Duke Eye Center/Dept. Ophthalmology, Center for Retinal Degenerations and Ophthalmic Genetic Diseases, Duke University School of Medicine, Durham, North Carolina, United States
  • Emily Brabbit
    Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
  • Alfonso Senatore
    Duke Eye Center/Dept. Ophthalmology, Center for Retinal Degenerations and Ophthalmic Genetic Diseases, Duke University School of Medicine, Durham, North Carolina, United States
  • Shyamtanu Datta
    Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
  • Neena B Haider
    Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Alessandro Iannaccone, None; Emily Brabbit, None; Alfonso Senatore, None; Shyamtanu Datta, None; Neena Haider, Ocugen (F)
  • Footnotes
    Support  Research to Prevent Blindness, Inc. New York, NY (Unrestricted grant to Duke Eye Center), Duke Retinal Degenerations Research Fund, and Duke Retina Genetics Research Fund, NEI grants R01-EY017653 and P30-EY003790, American Macular Degeneration Foundation, Ocugen
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1954. doi:
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      Alessandro Iannaccone, Emily Brabbit, Alfonso Senatore, Shyamtanu Datta, Neena B Haider; Comparison between human NR2E3-related disease and murine retinal characteristics identifies interspecies imaging correlates of key histological findings in rd7 mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1954.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize the nummular (coin-shaped) and drop-like shaped intra-retinal hyper-reflective formations (irHRFs) seen along the vascular arcades on spectral domain optical coherence tomography (SD-OCT) in patients with recessive NR2E3-related disease by comparing SD-OCT findings and histological sections in the equivalent rd7mouse model.

Methods : SD-OCTs of 6 patients age harboring homozygous or compound heterozygous NR2E3 mutations resulting in the Enhanced S-Cone Syndrome (ESCS) have been retrospectively evaluated (n=3 9-16yo and n=3 56-69yo, which correspond to mouse age ranges between post-natal day 7 and 3 months and 18-24 months, respectively). Mice with a homozygous Nr2e3 deletion (rd7) were imaged in vivo by SD-OCT, and representative histological retinal tissue sections were compared to SD-OCT findings in both species.

Results : SD-OCTs at the vascular arcades exhibited various types and sizes of nummular and drop-like shaped irHRFs in all patients. In a 9yo ESCS child without pigmentary deposits, irHRFs were mostly nummular, and at the level of the middle retina. Fainter drop-like shaped irHRFs were seen in the outer retinal third. In 2 older children who had already developed nummular deep pigment deposits, irHRFs persisted and were brighter. In adult patients with more confluent nummular deep pigment deposits at the arcades, the irHRFs persisted, were more numerous, and had the same features of the nummular and drop-like shaped middle and outer retinal irHRFs seen in earlier stages. These lesions correspond on SD-OCT to the photoreceptor rosettes and whorls seen on rd7 histological sections. However, unlike in rd7 mice in which these formations fade over time and exhibit little pigmentary reaction, ESCS patients with intermediate to advanced disease stage exhibit a growing number of increasingly brighter irHRFs.

Conclusions : The irHRFs seen on SD-OCT in patients with recessive NR2E3-related disease correspond to the rosettes and whorls seen on histological sections in rd7 mice. As these formations degenerate and become pigmented in humans, the irHRFs at the arcades increase and become brighter. With the caveat of a different pattern of evolution of irHRFs in human late disease stages, these findings validate further the rd7 mouse model for the understanding and forthcoming treatment of ESCS-related disease.

This is a 2020 ARVO Annual Meeting abstract.

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