Figure 6.

TRPV1 feedback involves the PI3K/AKT axis. (A) Feedback recovery of negative pressure to baseline does not occur in PI3K null lenses. GSK was used to activate TRPV4 and cause the surface pressure to go negative. However, in contrast to the response of wild-type lenses (Fig. 4A), the pressure remained negative in the absence of PI3K. This implies that PI3K activation occurs in the feedback loop initiated by TRPV1 to restore pressure to baseline. (B) Feedback recovery of negative pressure to baseline did not occur when AKT was inhibited. Therefore, AKT activation also occurs in the feedback loop initiated by TRPV1 to restore pressure to baseline. Moreover, initial blockade of AKT with AKTi did not affect the control pressure. Together with our previous studies, this observation suggests that all feedback steps from TRPV1 activation through activation of AKT have low basal activity.