Figure 9.

Schematic mechanisms leading to neuritogenesis during retinal degeneration. Activation in RA signaling, including RA, CRABPII, and RARs/RXRs, activates neuritogenesis during LIRD. Exogenous administration of RA initiates neuritogenesis in control mouse retinas and accelerates neuritogenesis in LIRD mouse retinas, while citral partially inhibits neuritogenesis. Meanwhile, RXRs directly interact with αCaMKII and βCaMKII, and the activity of RXRs is regulated by CaMKII signaling. LIRD up-regulates the AMPAR GluA2 subunit and decreases the ratio of αCaMKII/βCaMKII proteins, which increases the activity of RXRs. RXR agonist SR11237 initiates neuritogenesis, while RXR antagonist UVI3003 completely prevents neuritogenesis.