Abstract
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 (TGFβ) superfamily, that includes TGFβ 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 TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ 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.
Highlights
A functional and resilient visual system, durable to potential insults, is crucial for rapid interpretation of an animal’s surroundings
Our studies identify the morphogen Decapentaplegic (Dpp) and its mammalian homologues Bone Morphogenetic Protein (BMP)/TGFβ as important regulators of retinal tissue survival post injury (Fig 5)
We find that the response to these hemocyte derived ligands in the retina is dynamic: in Elav+ cells, Smox nuclear translocation is detected first after damage, while Mad phosphorylation occurs later and correlates with Daughters against Dpp (Dad)::GFP expression, consistent with Mad-mediated induction of Dad, as described previously in literature [36,53,77]
Summary
A functional and resilient visual system, durable to potential insults, is crucial for rapid interpretation of an animal’s surroundings. In both mammals and insects, the visual system contains a specific organization of structures; a lens to focus incoming light, a fluid filled vitreous, photoreceptors to sense and transmit light sensing signals to the optic lobes, pigmented cells to prevent diffraction, and immune cells adjacent to the tissue to mediate the damage response [1]. Photoreceptors that make up these systems become postmitotic in early maturation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
