Structure–function analysis of rods and cones in juvenile, adult, and aged C57BL/6 and Balb/c mice

Abstract

To determine whether the photoreceptors change structurally and functionally during aging, and to analyze whether pigmentation in the retinal pigment epithelium might be a contributing factor. Young, adult, and aged C57BL/6 and Balb/c mice (1, 4, and 17 months of age) were housed under a 12-h light/12-h dark cycle, with an ambient light intensity at the eye level of the mice of 85 +/- 18 lux. Scotopic single-flash and photopic-flicker electroretinograms (ERGs) after complete dark adaptation were used to assess rod and cone function, respectively. Numbers of rod photoreceptors were counted in plastic sections, and rhodopsin levels were measured using absorption difference spectrophotometry. Numbers and types of cones were determined using lectin staining in retinal flatmounts and cone-specific antibodies in radial frozen sections. Young pigmented C57BL/6 and nonpigmented Balb/c mice had similar numbers of rods. In both mouse strains, there was an overall decline in rod photoreceptor number during aging, which was more pronounced in albino mice. Rod cell numbers correlated with a drop in the overall amount of rhodopsin and a reduction in the maximum a-wave of the rod ERG. The number of short-wavelength cones was unaffected by age and pigmentation, whereas an age-related decline was observed in mid-wavelength (MWL) cones in albino, but not in pigmented mice. In contrast, MWL cone function was reduced during aging in both strains. Flicker-fusion frequency was determined to be approximately 10 Hz lower in albino animals, which is due to prolonged b-waves in these ERGs. Age-related changes were found in both photoreceptor systems, rods and cones, and in both pigmented and nonpigmented mice. However, rod photoreceptors appear to be more susceptible to both aging and the lack of pigmentation, when compared to cones. These results may help as we begin to understand certain age-related retinal diseases.

Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction

“…5B). The ERG responses of normal animals under both scotopic and photopic conditions were similar to those reported previously for aged pigmented mice (18). These data indicate that rod photoreceptor function is compromised in the cfh Ϫ/Ϫ mice, as shown by the reduction in amplitude and change in slope of the a-wave of the ERG.…”

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

“…1 B and C). These results suggest that the functional deficit seen in the young adult CA XIV-null mice is not progressive, but that the background strain has an age-related decline that is seen in both the wild-type and mutant mice (13).…”

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

“…Effects on Control APB mice were much smaller. In previous studies by other investigators, the amplitudes of dark-adapted a-waves and b-wave were found to be reduced as mice aged for both C57BL/6 mice (pigmented mice) and Balb/c mice (albino mice) (Gresh et al, 2003;Li et al, 2001). Between four and 17 months of age, there was a substantial loss of rod photoreceptors (more in the albino mice), which contributed to the reduced ERG amplitudes.…”

“…Between four and 17 months of age, there was a substantial loss of rod photoreceptors (more in the albino mice), which contributed to the reduced ERG amplitudes. But aging effects have been less obvious for cones, whose counts (middle wavelength) were reduced in aged Balb/c mice, but not in C57BL/6 mice (Gresh et al, 2003;Jacobs and Williams, 2007;Li et al, 2001). Cone-driven flash ERGs were found to be reduced in mice that are a year old, and light-adapted flicker ERG amplitudes were affected, but only mildly in the pigmented mice (Jacobs et al, 2007;Li et al, 2001).…”