Photoreceptor cell degeneration in Abcr (-/-) mice

Abstract

Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency in Abcr is associated with substantial accumulations of lipofuscin pigments in retinal pigment epithelial (RPE) cells. To observe for photoreceptor cell degeneration in these mutant mice, outer nuclear layer (ONL) thickness was measured at 200 mum intervals superior and inferior to the optic nerve head. ONL width in Abcr (-/-) mouse was reduced at 8-9 month and 11 and 13 months relative to Abcr ( +/+ ) mice; thinning was more pronounced centrally and in superior retina. The numbers of photoreceptor nuclei spanning the width of the outer nuclear layer were also reduced. No evidence of age-related ONL thinning was observed in Abcr (+/+) mice at these ages. We conclude that albino Abcr (-/-) mice exhibit progressive photoreceptor cell loss that is detectable at 8 months of age and that has worsened by 11 and 13 months of age. The measurement of ONL thickness is an established approach to assessing photoreceptor cell integrity and can be used in preclinical studies using Abcr (-/-) mice.

Fig. 61.1

Representative light micrographs of Abcr^+/+ and Abcr^−/− mouse retinas. Images of inferior hemisphere along the vertical meridian; age 9 months. Insets, higher magnification images obtained in the regions indicated. ONH, optic nerve head; GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. Magnification bar, 50 μm

Fig. 61.2

Quantification of outer nuclear layer (ONL) thickness in Abcr^+/+ and Abcr^−/− mice at age 5 month (a), 8–9 months (b) and 11–13 months (c). Measurements are plotted as a function of distance from the optic nerve head (ONH) in the inferior and superior hemispheres. Mean ± SEM; numbers of mice presented in parentheses