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Debarshi Mustafi, Christel Genoud, Kiichiro Okano, Andreas Engel, Krzysztof Palczewski; Impaired Cone Photoreceptor Phagocytosis Contributes to Retinal Degeneration in a Mouse Model of Enhanced S-cone Syndrome. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1823.
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Enhanced S-cone syndrome (ESCS) is a progressive retinal degeneration characterized by excess numbers of S-cones and decreased L/M cone function, together with nearly absent rod function. Although putative mutations that underlie ESCS have been well described, the pathophysiology of this disease has yet to be elucidated.
The experimental model that recapitulated the human ESCS phenotype was the mouse with a knockout of the neural retina leucine zipper (NRL) transcription factor. Both imaging and biochemical methods were used to identify the aberrant cone phagocytotic process that apparently underlies the degeneration in ESCS. Of note is the use a new imaging method for visual science research, a hybrid scanning electron microscopy (SEM) technique called serial block face (SBF) imaging. This involved collecting serial sections of retina for three-dimensional reconstructions to identify aberrant phagocytosis by the retinal pigmented epithelium (RPE).
Spectral-domain three-dimensional optical coherence tomography revealed a global retinal layer disruption caused by ESCS. Further probing by confocal and SEM imaging showed disrupted packing and aberrant photoreceptor structures with enlarged heads adjacent to the RPE. These enlarged heads resulted from impaired phagocytosis as evidenced by subsequent SBF-SEM imaging and biochemical staining showing an absence of phagosomes in the outer segment and RPE retinal layers.
A highly collaborative imaging and biochemical approach offered the first insight into a precipitating aberrant phagocytosis process that leads to the retinal degeneration seen in ESCS. This finding emanated from methodology not commonly used in vision research that presents a new avenue for investigating the structural basis of retinal diseases.
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