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Yingxiang Huang, Huiming Xia, John D Ash, ; Fluid transport defects in a mouse model of X-linked juvenile retinoschisis (XLRS). Invest. Ophthalmol. Vis. Sci. 2014;55(13):6312.
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We have previously reported a novel Rs1-null mutation (Rs1-E4E5) that was found in our mouse colony. Affected males display characteristic XLRS phenotypes. The purpose of this study was to characterize the natural history of disease in this model of human X-linked juvenile retinoschisis (XLRS).
Optical coherence tomography (OCT) and angiography were used to investigate the morphological change in vivo from 14 days to 6 months of age. Retinal function was evaluated by electroretinogram (ERG) recordings (Diagnosys, Littleton, MA) to measure a-, b-, and c-waves. Histological analysis of hematoxylin and eosin (H&E) stained sections were used to evaluate morphology.
Morphological abnormality in the retina was apparent beginning at postnatal day14 including schisis in the INL that quickly spread to the outer nuclear layer (ONL). OCT results revealed that the schisis phenotype varied significantly over time. The first schisis occurred around P14 in the inner nuclear layer (INL) and ranged in severity from a “moth eaten” appearance to very large cysts. Subsequent to the INL schisis, many animal developed severe retinal detachment. OCT analysis suggested the presence of channels for fluid movement between the INL schisis and subretinal spaces. Histologic examination of mutant mice suggests that the outer limiting member was not intact at the sites of retinal detachment.
The dynamic changes in our mouse model reproduce many characteristics of human XLRS including dynamic INL schisis and retinal detachment. The progress of schisis from the INL to the ONL and eventually to the subretinal space suggests that a primary cause of disease is defective fluid management by Müller cells leading first to fluid accumulation in the INL causing cyst formation. The fluid can filter into the ONL and to the subretinal space causing retinal detachment. The detachments can recover presumable by fluid transport through the RPE.
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