PT - JOURNAL ARTICLE AU - Torero Ibad, Raoul AU - Mazhar, Bilal AU - Vincent, Clémentine AU - Bernard, Clémence AU - Dégardin, Julie AU - Simonutti, Manuel AU - Lamonerie, Thomas AU - Di Nardo, Ariel A. AU - Prochiantz, Alain AU - Moya, Kenneth L. TI - OTX2 Non-Cell Autonomous Activity Regulates Inner Retinal Function AID - 10.1523/ENEURO.0012-19.2020 DP - 2020 Sep 01 TA - eneuro PG - ENEURO.0012-19.2020 VI - 7 IP - 5 4099 - http://www.eneuro.org/content/7/5/ENEURO.0012-19.2020.short 4100 - http://www.eneuro.org/content/7/5/ENEURO.0012-19.2020.full SO - eNeuro2020 Sep 01; 7 AB - 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.