Figure 7.
Effect of retinal microglial depletion on functional electroretinographic responses. ERG recordings were obtained from adult (2- to 3-month-old) female: (1) nondepleted TG mice (TG control; n = 17 animals), (2) mice depleted of microglia for 5 d (TG Depleted 5 d; n = 5 animals), and (3) mice depleted of microglia for 30 d (TG Depleted 30 d; n = 13 animals). A, Dark-adapted a-wave responses were nonsignificantly changed at 5 d (p = 0.12) but significantly decreased at 30 d (p < 0.0001). Dark-adapted b-wave responses were progressively decreased at both 5 and 30 d (p < 0.0001). B, Light-adapted responses: a-wave responses were unchanged at 5 d (p = 0.87) but decreased at 30 d (p < 0.0001); b-wave responses were progressively decreased at 5 d and further at 30 d (p < 0.0001). In both light- and dark-adapted responses, b–a wave amplitude ratios are progressively decreased with duration of depletion. C, ERG recordings were obtained from adult (2- to 3-month-old) C57BL6 WT mice that were either tested without TAM administration or tested followed 30 d of TAM administration (n = 6 female 8-week-old animals in each group). Comparison of dark-adapted a- and b-wave responses revealed no changes secondary to TAM administration. Comparison of light-adapted a-wave response showed no significant changes but slightly and significantly decreased b-wave responses after TAM administration (graphical data in B and C are represented as mean ± SEM; *indicates comparisons relative to baseline using multiple t tests, corrected for multiple comparisons using the Holm–Sidak method, for α < 0.05). D, Visual acuity capabilities of age-matched adult (2- to 3-month-old) TG versus TG-depleted 30 d mice were evaluated by automated assessment of optomotor responses (n = 4 female 8-week-old animals in each group). Sinusoidal gratings, rotating in a virtual cylinder at 12°/s, were presented at different spatial frequencies to each awake and unrestrained animal tested, and resulting optomotor responses were quantitated from the tracking of head movements as the ratio of the time during which head movement occurred in the same direction with stimulus movement to the time during which it occurred in the opposite direction (Tcorrect/Tincorrect). Data points indicate median ratios at each grating spatial frequency with the color areas indicating the upper and lower quartiles of the dataset. Measurements from functionally blind 6-month-old rd10 mice (yellow areas) served as a negative control. Under scotopic conditions (left), the response curve of TG Control mice (pink symbols) at lower frequencies matched that of TG-depleted mice (green symbols) closely, whereas at higher frequencies (>0.15 cycles/°), the response curve for TG Depleted 30 d mice was slightly and nonsignificantly lower than that of TG Control mice. Under photopic conditions (right), the response curve of the response curve for TG Depleted 30 d mice was slightly, and nonsignificantly lower, than that of TG Control mice. Estimations of visual threshold, defined as the spatial frequency corresponding to 25% of the maximum optomotor response, was similar between depleted and nondepleted animals, for both scotopic and photopic conditions (p > 0.05, t test; bottom).