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.