| Autor: |
Telias M; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Sit KK; Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Frozenfar D; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Smith B; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Misra A; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA., Goard MJ; Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA., Kramer RH; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. |
| Abstrakt: |
Rod and cone photoreceptors degenerate in retinitis pigmentosa (RP). While downstream neurons survive, they undergo physiological changes, including accelerated spontaneous firing in retinal ganglion cells (RGCs). Retinoic acid (RA) is the molecular trigger of RGC hyperactivity, but whether this interferes with visual perception is unknown. Here, we show that inhibiting RA synthesis with disulfiram, a deterrent of human alcohol abuse, improves behavioral image detection in vision-impaired mice. In vivo Ca 2+ imaging shows that disulfiram sharpens orientation tuning of visual cortical neurons and strengthens fidelity of responses to natural scenes. An RA receptor inhibitor also reduces RGC hyperactivity, sharpens cortical representations, and improves image detection. These findings suggest that photoreceptor degeneration is not the only cause of vision loss in RP. RA-induced corruption of retinal information processing also degrades vision, pointing to RA synthesis and signaling inhibitors as potential therapeutic tools for improving sight in RP and other retinal degenerative disorders. |
