Purchase this article with an account.
S. Lindemann, K. Kamino, D. Wedekind, H. Hedrich, R. Winter, W. Löscher, R. Gockeln; Histological Examination in a Blind-deafness Rat Mutant – A Rodent Model for Usher Syndrome Phenotype 1 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2820.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Usher syndrome (USH) is the most common retinitis pigmentosa syndrome. Patients with USH1 have profound congenital hearing impairment, vestibular dysfunction, and progressive retinal degeneration with later onset. The cause of the pathology in USH is unknown and no animal models with the complete phenotype have been available for investigation. We report a rat model of USH phenotype 1, LEW/Ztm-ci2 (ci2). Ci2 homozygotes exhibit lateralized circling, locomotor hyperactivity, ataxia, opisthotonus, a complete sensorineural hearing loss and vestibular defects. Methods: For the present study, age- and sex-matched homozygous ci2+/+ and heterozygous ci2+/- animals were used. In addition non-affected LEW/Ztm rats (wt) were used as controls. To study the retinal morphology, we used two rats of each of the three types. The eyes were enucleated and fixed with formaldehyde. After this the eyes were dissected sagittaly, the lenses removed and embedded in paraffin. Semi-thin sections were cut using a microtome and stained with HE. Results: Histological examination of the retinal circumference from both eyes showed a complete loss of the outer segments and the outer nuclear layer of the peripheral retina in ci2 mutants. In contrast to the retinal circumference, the thickness of the outer segments and the outer nuclear layer of the central retina was decreased, compared to the wt, whereas, retinal pigment epithelium (RPE) and chorioid did not show any abnormalities. The choriocapillaris were highly fenestrated and appeared the same as in wt – eyes. In the area of the optic nerve head, the central retinal artery branched into a few main branches and formed the vascular bed, seen also in wt rats. Electroretinography examinations in adult rat mutants at PW40 show the scotopic and photopic electroretinogram only of remainder responses or was complete absent, whereas the wt still had normal ERG responses. Conclusions: The histological findings of our investigation correlates well with the electrophysiological defects found in the ci2 rat mutants. This findings will, together with the behavioral phenotype, establish the ci2+/+ rat mutant as the rodent model for Usher syndrome, phenotype1.
This PDF is available to Subscribers Only