Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina

Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGF beta) superfamily, that includes TGF beta and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGF beta/BMP signaling, as supplementation of BMP4 or inhibition of TGF beta using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.

Automated summary

Retinal homeostasis relies on the intricate coordination of cell death and survival in response to stress and damage, with Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue, Transforming Growth Factor-beta (TGF beta) superfamily, identified as key mediators in this process. A dynamic response of retinal cells to Dpp signaling is observed, where stimulation of Saxophone/Smox signaling promotes apoptosis in the early phase while stimulation of the Thickveins/Mad axis promotes tissue repair and survival in a later stage. This dual role is conserved in the mammalian retina through the TGF beta/BMP signaling pathway.