Figure 2. Tamoxifen administration before acute LI results in near complete rescue of structural and functional retinal damage. Adult mice were administered daily oral tamoxifen (added to standard animal chow, 500 mg/kg chow, estimated intake of 80 mg/kg body weight/d) 1 week before LI and thereafter; control animals were fed standard chow without tamoxifen at all time points. A, Total retinal thickness in the central retina (radius 600 μm around optic nerve) as measured by OCT are depicted in heat maps; control animals demonstrate extensive retinal thinning (blue areas) at 7 d after LI that was absent in tamoxifen-treated animals. B, Individual OCT B-scans in the superior retina demonstrated the following: (1) loss of outer segments, (2) thinning of the ONL layer (white box), and (3) emergence of areas of retinal detachment (white arrow); these features were absent in tamoxifen-treated animals (red box). C, Quantification of mean OCT-derived total (top row) and outer retina thickness (bottom row) in inner (pink quadrants) and outer (yellow quadrants) in the horizontal (left) and vertical (right) axes demonstrate marked thinning 7 d after LI in control animals (black lines) but no significant changes from baseline in tamoxifen-treated animals (red lines) (n = 27 eyes from 14 animals of mixed gender for each group, 2-way ANOVA). D, Prevalence of localized retinal detachments, scored at 7 d after LI, was significantly lower in tamoxifen-treated versus control groups (n = 27 eyes in each group in 3 independent experiments, χ2 statistic). E, ERG measurements of uninjured animals administered standard chow (control diet) versus oral tamoxifen for 14 d demonstrated that tamoxifen did not exert a large change on the magnitude of response amplitudes (2-way ANOVA, n = 6 animals in each group, 3 male and 3 female, 2.5–3 months old). F, ERG measurements in the LI model demonstrated that a- and b-wave amplitudes for dark- and light-adapted functional responses obtained 7 d after LI in tamoxifen-treated animals (red lines) were significantly greater than those in untreated controls (black dashed lines). a-wave amplitudes for both light- and dark-adapted responses in tamoxifen-treated animals were statistically similar to uninjured controls (p > 0.99 for both comparisons), indicating full protection. b-wave amplitudes approached those in uninjured controls, but did not reach full protection (p < 0.05 for both comparisons). Top, Data points and error bars represent mean and SEM; n = 12, 7, and 7 animals for uninjured control, untreated control 7 d after LI, and tamoxifen-treated animals 7 d after LI, respectively. Bottom, Difference in column means between the three groups, all comparisons made with two-way ANOVA, error bars indicate 95% confidence intervals.