Retinoic Acid Induces Hyperactivity, and Blocking Its Receptor Unmasks Light Responses and Augments Vision in Retinal Degeneration.
Neuron
; 102(3): 574-586.e5, 2019 05 08.
Article
en En
| MEDLINE
| ID: mdl-30876849
ABSTRACT
Light responses are initiated in photoreceptors, processed by interneurons, and synaptically transmitted to retinal ganglion cells (RGCs), which send information to the brain. Retinitis pigmentosa (RP) is a blinding disease caused by photoreceptor degeneration, depriving downstream neurons of light-sensitive input. Photoreceptor degeneration also triggers hyperactive firing of RGCs, obscuring light responses initiated by surviving photoreceptors. Here we show that retinoic acid (RA), signaling through its receptor (RAR), is the trigger for hyperactivity. A genetically encoded reporter shows elevated RAR signaling in degenerated retinas from murine RP models. Enhancing RAR signaling in healthy retinas mimics the pathophysiology of degenerating retinas. Drug inhibition of RAR reduces hyperactivity in degenerating retinas and unmasks light responses in RGCs. Gene therapy inhibition of RAR increases innate and learned light-elicited behaviors in vision-impaired mice. Identification of RAR as the trigger for hyperactivity presents a degeneration-dependent therapeutic target for enhancing low vision in RP and other blinding disorders.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Degeneración Retiniana
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Células Ganglionares de la Retina
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Tretinoina
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Visión Ocular
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Receptores de Ácido Retinoico
Límite:
Animals
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Humans
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos