Inhibition of GABAA-ρreceptors induces retina regeneration in zebrafish  

作　　者：Matthew R.Kent Nergis Kara James G.Patton 

机构地区：[1]Department of Biological Sciences,Vanderbilt University,Nashville,TN,USA

出　　处：《Neural Regeneration Research》2021年第2期367-374,共8页中国神经再生研究（英文版）

基　　金：grants from the NIH R01EY024354-S1 and UO1 EY027265 to JGP;and T32 EY021453;additional support from the Stevenson family and Gisela Mosig endowments to Vanderbilt University。

摘　　要：A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spontaneous regeneration.We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration.We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A(GABAA)receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration,as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells.Here,we show that inhibition of a pharmacologically distinct subset of GABAA receptors(GABAA-ρ)can also induce retina regeneration.Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration.Gene expression analyses indicate that inhibition of GABAA-ρreceptors induces a canonical retinal regenerative response.Our results support a model in which decreased levels of GABA,such as would occur after retinal cell death or damage,induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration.Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee(Protocol M1800200)on January 29,2019.

关 键 词：gamma aminobutyric acid MORPHOLINO Müller glia NEUROTRANSMITTER REGENERATION RETINA stem cells ZEBRAFISH 

分 类 号：R774.1[医药卫生—眼科]