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Joe Hollyfield, Vera Bonilha, Mary Rayborn, Brent Bell, Meghan Marino, Gerald Fishman; Retinal Histopathology in Eyes from a Patient with Stargardt Disease Caused by Compound Heterozygous ABCA4 Mutations. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1363. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the histopathology of the retina in donor eyes from a patient with Stargardt disease caused by ABCA4 mutations.
Eyes from a 66 year-old female were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in PBS within 18 hours postmortem. Globes were evaluated with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for electron microscopy and immunocytochemistry. Three age-similar normal eyes were used as controls. Genetic testing was done by both SSCP and direct sequencing of the ABCA4 gene.
Donor ABCA4 gene analysis showed three heterozygous mutations in exon 42, namely Gly1961Glu, IVS41-43 C>A, and IVS41-11 G>A, and a heterozygous IVS46+2 C>G mutation in exon 46. All imaging modalities showed peripheral areas with few bone spicules. The area surrounding the optic nerve showed evidence of RPE atrophy as visualized by SLO autofluorescence. The fovea and optic nerve were clearly identified in OCT. Histology showed a degenerated retina with only a few disorganized photoreceptors and the absence of RPE in the perimacula. The macula was severely degenerated, with little evidence of any retinal cell layer including the RPE. In contrast, stratified nuclear layers were observed in the retinal periphery. In the periphery, the RPE was present and thicker than normal, but lacked melanin pigment. Cones were present in small areas in the perimacular region that labeled with opsin and arrestin antibodies. Disorganized rhodopsin labeled rods were detected in the perimacular region and in the periphery. Calbindin labeled second order neurons were sparse in the perimacular region but were more abundant in the periphery. No labeling with any of the markers used was evident in the macula due to extensive neuronal loss. Reactive glia labeled with GFAP was increased in the perimacular region and periphery of the donor tissue. Autofluorescent material in the perimacular and macular region was significantly reduced in areas where the RPE remained. In the periphery, the RPE was hypertrophy and the autofluorescence was more intense.
The histopathology of the retina in a patient with Stargardt disease due to compound heterozygous ABCA4 mutations displayed a highly degenerate macular retina and preservation of some cone and rod photoreceptors in the perimacular region and periphery.
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