Cell Transplantation to Arrest Early Changes in an Ush2a Animal Model
ABSTRACT Purpose. Usher's syndrome is a combined deafness and blindness disorder caused by mutations in several genes with functions in both the retina and the ear. Here the authors studied morphologic and functional changes in an animal model, the Ush2a mouse, and explored whether transplantation of forebrain-derived progenitor cells might affect the progress of morphologic and functional deterioration. Methods. Ush2a mice were tested at postnatal days (P) 70 to P727 using an optomotor test, which provides a repeatable method of estimating rodent visual acuity and contrast sensitivity. A group of mice that received grafts of forebrain-derived progenitor cells at P80 was tested for up to 10 weeks after grafting. At the end of testing, animals were killed, and eyes were processed for histology. Results. The optomotor test showed that both acuity and contrast sensitivity deteriorated over time; contrast sensitivity showed a deficit even at P70. By contrast, photoreceptor loss was only evident later than 1 year of age, though changes in the intracellular distribution of red/green cone opsin were observed as early as P80. Mice that received transplanted cells performed significantly better than control mice and no longer demonstrated abnormal distribution of red/green opsin where the donor cells were distributed. Conclusions. This study showed that vision impairment was detected well before significant photoreceptor loss and was correlated with abnormal distribution of a cone pigment. Cell transplantation prevented functional deterioration for at least 10 weeks and reversed the mislocalization of cone pigment.
SourceAvailable from: Laura Fernández-Sánchez[Show abstract] [Hide abstract]
ABSTRACT: Purpose The P23H rhodopsin mutation is an extensively studied model of ADRP. We evaluated the anatomical changes using SD-OCT and correlate the findings and retinal thickness values with immunocytochemistry. Functional changes were analyzed Methods Heterozygous P23H pigmented transgenic rats aged from P18 to P180 were studied. LE rats bred with Sprague Dawley (SD) 1 month old served as wild type controls. Visual acuity and contrast sensitivity evaluation was performed every month. Corneal ERGs were recorded under scotopic and photopic conditions. Retinal thicknesses at different levels (total thickness, ONL + RPE, ONL and IPL), fundus autofluorescence (FAF) and fluorescein angiography was performed in 3 animals at P150 using Spectralis OCT and HRA (Heidelberg Engineering, Germany). Retinas were immunostained for ICC. Results Retinal thicknesses diminution was seen in OCT sections, with a clear loss of ONL and morphological modifications. Statically differences were found between groups in all evaluated thicknesses. In the P23H rats, change in FAF was noted comparing to control group, as sparse autofluorescent dots. No relevant changes were observed in the angiography pattern. ICC showed a progressive decrease in ONL thickness. Functional changes were progressive with time. Conclusion Anatomical changes in pigmented P23H can be observed using SD-OCT and immunocytochemistry, with a good correlation between their values. SD-OCT and FAF are important tools for research in retinal degenerations.Acta ophthalmologica 08/2013; 91(s252). DOI:10.1111/j.1755-3768.2013.F016.x · 2.51 Impact Factor
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ABSTRACT: The Usher syndrome (USH) is the most prevalent cause of inherited deaf-blindness. Three clinical subtypes, USH1-3, have been defined, and ten USH genes identified. The hearing impairment due to USH gene defects has been shown to result from improper organisation of the hair bundle, the sound receptive structure of sensory hair cells. In contrast, the cellular basis of the visual defect is less well understood as this phenotype is absent in almost all the USH mouse models that faithfully mimic the human hearing impairment. Structural and molecular interspecies discrepancies regarding photoreceptor calyceal processes and the association with the distribution of USH1 proteins have recently been unravelled, and have led to the conclusion that a defect in the USH1 protein complex-mediated connection between the photoreceptor outer segment and the surrounding calyceal processes (in both rods and cones), and the inner segment (in rods only), probably causes the USH1 retinal dystrophy in humans.Comptes rendus biologies 03/2014; 337(3):167-77. DOI:10.1016/j.crvi.2013.12.004 · 1.68 Impact Factor
Dataset: Cuenca et al 2014 Frontiers NA OCT