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Cellular origin of fundus autofluorescence in patients and mice with a defective NR2E3 gene
1Bernard & Shirlee Brown Glaucoma Laboratory, Edward S Harkness Eye Institute, New York 10032, USA.
Aim:
To characterise new clinical features in a family with enhanced S-cone syndrome (ESCS) and investigate the pathogenesis of these clinical features in the homozygous Nr2e3(rd7) (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. Colour 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 colocalised to the same cells within the retina rosettes.
Conclusions:
The 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. These data are consistent with macrophage infiltration contributing to the hyperautofluorescent spots found in our patients.
Insights
Enhanced S-cone syndrome (ESCS) involves NR2E3 gene mutations. Macrophage infiltration in retinal rosettes may cause hyperautofluorescent spots in patients with this rare eye condition.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Enhanced S-cone syndrome (ESCS) is a rare inherited retinal disorder.
- The NR2E3 gene plays a crucial role in photoreceptor development and function.
Observation:
- Clinical characterization of four patients with ESCS revealed novel features.
- Retinal imaging showed rosette-like lesions, and OCT confirmed similarities to rd7 mouse models.
- Immunohistochemistry in rd7 mice demonstrated colocalization of macrophages and autofluorescent material within retinal rosettes.
Findings:
- A homozygous R311Q mutation in the NR2E3 gene was identified in the affected family.
- Macrophage infiltration within retinal rosettes was observed in rd7 mice, containing autofluorescent material.
- These findings suggest a potential pathogenic mechanism for hyperautofluorescent spots in ESCS patients.
Implications:
- The study elucidates the clinical presentation and potential pathogenesis of ESCS.
- It highlights the role of macrophage infiltration in the development of retinal abnormalities in ESCS.
- This research provides insights into NR2E3-associated retinal diseases and potential therapeutic targets.
