ObjectiveTo observe the effect of simulated microgravity on the photopic negative response (PhNR) of full-field flash ERG in adult mice.MethodsIn an experimental study, forty-eight adult male C57BL/6J mice (48 eyes) were randomly divided into model and control groups. Model mice were further divided into three subgroups of 8 each: tail-suspended for 15 days (subgroup A), tail-suspended for 30 days (subgroup B), and tail-suspended for 30 days followed by returning to normal position for 30 days (subgroup C). The three control subgroups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60 days. The mice were immediately examined using ERG-PhNR, flash VEP, OCT and visually-guided behavior in vivo, and subsequently sacrificed to analyze the retinal histology in vitro. PhNR amplitude was measured from baseline to PhNR trough. N1 peak-time and N1-P1 amplitude of VEP was analyzed. The escape duration was used to quantitatively evaluate the visual function of mice. In addition, inner retinal thickness was analyzed by OCT imaging. Data were compared by the independent sample t-test.ResultsPhNR amplitude in the model subgroup A was obviously lower than the corresponding control subgroup, the difference was statistically significant (t=−3.196, P＜0.01). There was no significant difference in PhNR amplitude between the model subgroup B or C and the corresponding control subgroup (t=−1.976, 0.285; P＞0.05). There was no significant difference in FVEP N1 peak-time or N1-P1 amplitude between any of the three model subgroups and the corresponding control subgroup (P＞0.05). There was no significant difference in OCT-measured inner retinal thickness between any of the three model subgroups and the corresponding control subgroup (t=−0.461, 2.073, −0.402; P＞0.05). The three model subgroups showed almost normal retinal structure, including the retinal ganglion cell, inner pexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, ellipsoid zone and RPE. There was no significant difference in visually-guided escape time between any of the three model subgroups and the corresponding control subgroup (t=−0.637, −0.955, 1.297; P＞0.05).ConclusionVia tail-suspension, short-term simulated microgravity can affect the PhNR of flash ERG; however, the change is reversible and does not affect visual function of mice.