Cellular origin of fundus autofluorescence in patients and mice with a defective NR2E3 gene

Abstract

Aim-To characterize new clinical features in a family with enhanced S-cone syndrome (ESCS) and investigate the pathogenesis of these clinical features in the homozygous Nr2e3 rd7rd7 (rd7) mutant mice.Methods-Four patients from an affected family were included for genotypic and phenotypic study. Eye tissues from rd7 mice were used to detect a possible relationship between macrophages and autofluorescent material by immunohistochemistry (IHC) staining.Results-Homozygous mutation in R311Q in NR2E3 was detected in this family. Color photographs revealed that white dots do not correlate to hyperautofluorescent spots seen in autofluorescence imaging of the macula. OCT showed rosette-like lesions similar to those found in rd7 mice histology sections. From IHC analysis, we observed that F4/80 (a pan macrophage marker), and autofluorescence were co-localized to the same cells within the retina rosettes.Conclusions-Retinal structure of a young ESCS patient with homozygous R311Q mutation in the NR2E3 gene is similar to that seen in the rd7 mice. The macrophages were found to contain autofluorescent materials in the retinal rosettes of rd7 mice. Our data are consistent with macrophage infiltration contributing to the hyper-autofluorescent spots found in our patients.

Double Concentric Autofluorescence Ring inNR2E3-p.G56R-Linked Autosomal Dominant Retinitis Pigmentosa

“…Indeed, in ESCS (GFS) patients, FAF examination showed hyperautofluorescent spots in both the macular area and mid-peripheral retina, 41,42 and OCT analysis correlated these hyperautofluorescent spots with the rosette-like lesions characteristic of GFS. 42 In conclusion, study findings suggest that this double concentric hyperautofluorescent ring, where the inner ring appears smaller and the outer ring larger in patients with more advanced disease, to be a highly penetrant FAF feature of NR2E3-p.G56R-linked ADRP. Its absence, however, does not exclude definitively the presence of the NR2E3-p.G56R mutation.…”

NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

“…The adRP-linked c.166G4A (p.G56R) mutation is present in a heterozygous state in 83 patients from eight independent families, accounting for approximately 1 to 2% of adRP cases [Gire et al, 2007]. In contrast to the adRP families and the patients carrying the c.119-2A4C mutation, who are reportedly of Western European/Near Eastern/Caucasian origin, the c.932G4A mutation is also present in the Japanese and Chinese populations, suggesting a mutational hotspot [Nakamura et al, 2002;Wang et al, in press]. Table 3 lists 14 polymorphisms; i.e., sequence variants not segregating with disease within families and present in control individuals.…”

Cone Vision Changes in the Enhanced S-Cone Syndrome Caused byNR2E3Gene Mutations

“…48,52 Another feature of young rd7 mice (among other mouse models 53 ) is the readily visible dysplasia across the entire retina; the white spots represent whorls and rosettes and are well-explored. 47,51,54 Although noninvasive imaging and postmortem histopathology have noted such changes in human NR2E3 disease, 15,55 it is less prominent a feature than in the mice. Retinal dysplasia in the mice is followed by retinal degeneration.…”