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

• Published in: PloS one 2021-10, Vol.16 (10), p.e0258872-e0258872
• Main Authors: Kramer, Joshua, Neves, Joana, Koniikusic, Mia, Jasper, Heinrich, Lamba, Deepak A
• Format: Article
• Language: English
• Subjects: Aging; Animals; Apoptosis; Apoptosis - physiology; Biology and Life Sciences; Bone morphogenetic protein 4; Bone morphogenetic proteins; Cell death; Cell survival; Damage detection; Drosophila; Drosophila Proteins - metabolism; Dynamic response; Fruit flies; Growth factors; Homeostasis; Homology; Immune system; Insects; Kinases; Mammals; Medical research; Medicine and Health Sciences; N-Methyl-D-aspartic acid; Ophthalmology; Photoreceptors; Proteins; Receptors, Transforming Growth Factor beta - metabolism; Research and Analysis Methods; Retina; Retina - metabolism; Retina - pathology; Retinal cells; Signal Transduction - physiology; Signaling; Social Sciences; Stem cells; Stimulation; Survival; Tissues; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Ultraviolet radiation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0258872

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.