CBR Member Shravan Chintala Publishes in PLoS ONE

CBR member Shravan Chintala, of the Eye Research Institute, recently published a paper studying if Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons (PLoS ONE, Volume 10, Article Number e0127776). DREAM stands for Downstream Regulatory Element Antagonistic Modulator, and is a protein that interacts with potassium channels in the membrane of a neuron. Coauthors on the study are ERI staff members Mei Cheng and Xiao Zhang. The article appears in PLoS ONE, an open access journal published by the Public Library of Science.

Below is the introduction to the paper (references removed). 


Activation of NMDA-type glutamate receptors (NMDARs) plays a pivotal role in synaptic transmission by allowing calcium entry into the neuronal cells. However, over-activation of NMDARs leads to a rise in intracellular calcium levels and promotes the degeneration of neuronal cells in the central nervous system (CNS), as well as in the retina. In support of this, a number of previous studies have documented that the activation NMDARs increases calcium influx and promote apoptotic death of RGCs, as well as of other neuronal cells in the retina. However, the intrinsic mechanisms that promote the degeneration of RGCs following the activation of NMDARs are still unclear.

Previous studies have reported that a rise in intracellular calcium leads to the modulation of a variety of target genes, and neuronal calcium sensing (NCS) proteins play an important role in this process. Four NCS proteins that belong to a group of K-channel interacting proteins 1 to 4 (KChIP-1 to -4) have been identified to date in the CNS. A member of this family, DREAM also known as calsenilin or KChIP-3, found to be expressed widely in sensory neurons in the CNS, where its high affinity binding to DRE (downstream regulatory element) sequences represses c-fos- mediated expression of downstream target genes. Although the function(s) of DREAM and its target genes are not completely understood, previous studies have shown that knockdown of DREAM increased NMDA-induced neuronal toxicity, while overexpression of DREAM offered neuroprotection. However, the role of DREAM in the retina under normal physiological conditions or following the over-activation of NMDARs has not been reported. Therefore, this study was designed to investigate whether DREAM is expressed in the retina, and whether the expression of DREAM plays a role in NMDA-mediated degeneration of retinal neurons. 

This research was supported by a grant from the National Eye Institute (R01EY07853), part of the National Institutes of Health