The Influence of NaIO(3)-Induced Retinal Degeneration on Intra-retinal Layer and the Changes of Expression Profile/Morphology of DA-ACs and mRGCS.
2013
Sodium iodate (NaIO3)-induced retina injury is one of models that is commonly used to study various retinal diseases caused by retinal pigment epithelium (RPE) injury such as AMD. Previous researches have revealed that RPE and photoreceptors are main impaired objects in this model. By comparison, intra-retinal layer has not been studied in detail after NaIO3 administration. In this study, we present evidences that intra-retinal neurons can be directly injured by NaIO3 at early stage and that the morphology had taken obvious changes, the decreased areas of dendritic fields of dopaminergic amacrine cells (DA-ACs), horizontal cells, and melanopsin-expressing retinal ganglion cells (mRGCs). Moreover, we found that miRNA 133b that was considered specifically to express in midbrain dopaminergic neurons was markedly upregulated in retinal DA-ACs after NaIO3 administration. The overexpression of mir-133b negatively regulated the expression of pitx3, an important transcription factor, and led to a series of deficits of DA-ACs such as TH and D2 receptor expression and DA producing, which may play a causative role in pathological events of horizontal cells and mRGCs. After mir-133b was interfered with mir-133b/RNAi, not only those deficits were rescued, but also the amplitude of b-wave and summed OPs of ERG were improved significantly. In conclusion, our data demonstrate, for the first time, that intra-retinal neurons can be directly injured by NaIO3 at early stage, and that mir-133b level effectively controls synaptic contacts or neural interactions among DA-ACs, horizontal cells, and mRGCs. Delivering mir-133b/RNAi intravitreally can rescue NaIO3-induced failure and improve visual function by restoring synaptic contacts.
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