TY - JOUR T1 - OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0012-19.2020 VL - 7 IS - 5 SP - ENEURO.0012-19.2020 AU - Raoul Torero Ibad AU - Bilal Mazhar AU - Clémentine Vincent AU - Clémence Bernard AU - Julie Dégardin AU - Manuel Simonutti AU - Thomas Lamonerie AU - Ariel A. Di Nardo AU - Alain Prochiantz AU - Kenneth L. Moya Y1 - 2020/09/01 UR - http://www.eneuro.org/content/7/5/ENEURO.0012-19.2020.abstract N2 - OTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting the survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single-chain anti-OTX2 antibody. Compared with control mice, the expression of this antibody by parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in 1-month-old mice with no alteration of the retinal structure or cell type number or aspect. The a-waves and b-waves measured by electroretinogram were also indistinguishable from those of control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude and a reduction in oscillatory potential, consistent with a change in inner retinal function. Our results show that interfering in vivo with OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity. ER -