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Melanie C W Campbell, Laura Emptage, Frank Corapi; Effects of Lafora disease on the retina of a transgenic mouse model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4319. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Lafora disease, also known as Lafora Progressive Myoclonus Epilepsy, is a fatal neurodegenerative disease causing seizures and reduction in brain function. The disease is characterized by the presence of polyglucosans called Lafora bodies, within the cells of the brain, skin, liver, muscles and sweat glands. These bodies and the effects of the disease on the retina of a mouse model of the disease are explored.
Eyes of Tg Malin knock-out mice, a model of Lafora disease (~2 years old) and control mice (C57BLK/6~ 1 month old) with confirmation of no retinal degenerations, were enucleated. Retinas were flat mounted and examined both unstained (Lafora n=3, control n=3) and stained (Lafora n=2, control n=2). The stained retinas were labelled with periodic acid Schiff-Diatase (PAS-D) for detection of Lafora bodies. Retinas were imaged using a Nikon transmission microscope fitted with a polarimeter and polarization and white light images of different locations were taken. Images focused at three different layers including the nerve fiber layer, the bipolar cell layer and the photoreceptor layer were taken. From the 16 polarization images, a Mueller matrix for each location and focus was calculated, from which different polarization properties were calculated and compared between control and affected retinas.
Lafora bodies were found within the anterior retinas of the Lafora model and not in controls. These bodies were similar in size to those reported in the brains of the model. There was also a significant difference between the model and control retinas for linear retardance for the anterior focus. Linear retardance was reduced significantly on average by 31% in the model (p<0.04). It is known that linear retardance of the retinal nerve fibre layer (RNFL) is proportional to its thickness . The large reduction in retardance observed here is much greater than the 12% reduction reported with age in the thickness of the ganglion cell complex (including RNFL) for the age difference between the models and controls.
Lafora bodies are present in the retina of the Tg Malin knock-out model of Lafora and are large enough to be detected without the use of adaptive optics. The reduction in the linear retardance suggests a thinning of the RNFL due to neurodegeneration associated with the disease. Retinal thinning could be used to help characterize Lafora disease in vivo.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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