Effect of light on global gene expression in the neuroglobin-deficient mouse retina

Abstract

Abstract. Several previous studies have raised controversy over the functional role of neuroglobin (Ngb) in the retina. Certain studies indicate a significant impact of Ngb on retinal physiology, whereas others are conflicting. The present is an observational study that tested the effect of Ngb deficiency on gene expression in dark-and light-adapted mouse retinas. Large-scale gene expression profiling was performed using GeneChip ® Mouse Exon 1.0 ST arrays and the results were compared to publicly available data sets. The lack of Ngb was found to have a minor effect on the light-induced retinal gene expression response. In addition, there was no increase in the expression of marker genes associated with hypoxia, endoplasmic reticulum-stress and oxidative stress in the Ngb-deficient retina. By contrast, several genes were identified that appeared to be differentially expressed between the genotypes when the effect of light was ignored. The present study indicates that Ngb deficiency does not lead to major alternations in light-dependent gene expression response, but leads to subtle systemic differences of a currently unknown functional significance.

Neuroglobin immunoreactivity in the human cochlea

“…Ngb overexpression in stroke animal models decreased the severity of functional and histological deficits (Khan et al, 2006; Sun et al, 2003; Wang et al, 2008). Studies in the Ngb knockout mouse model show that genetic elimination of Ngb does not affect core clock function (Hundal et al, 2012), and has a minor effect on light–induced retinal gene expression response (Ilmajarv et al, 2014). A recent report on the expression of Ngb in hippocampal sections obtained at autopsy from patients with Alzheimer’s disease shows that Ngb levels were increased in early and moderately advanced Alzheimer’s disease compared to controls, but declined to control levels when disease progressed to advanced stages, suggesting that Ngb levels may influence the progression of neurodegeneration (Sun et al, 2013).…”

Neuroglobin in Retinal Neurodegeneration: A Potential Target in Therapeutic Approaches

“…Despite studies reporting no effects of lack of NGB on light-induced cellular stress response [66] have raised doubts over the functional role of endogenous NGB in retinal physiology, several reports demonstrated a function of NGB exogenous overexpression in preventing retinal disease and/or in maintaining retinal structural and functional integrity upon stress exposure. Intriguingly, NGB overexpressing mice exposed to retinal ischemia-reperfusion (IR) injury showed significant preservation of retinal thickness [37].…”

Neuroglobin Expression Models as a Tool to Study Its Function

“…Furthermore, the functional significance of endogenous Ngb in the retina remains unclear. Endogenous Ngb is not thought to play a major role in retinal oxygen homeostasis and only has a minor effect on light-dependent gene expression ([88], Figure 4). These observations suggest only a subtle systemic role for Ngb.…”

“…These observations suggest only a subtle systemic role for Ngb. In addition, Ngb is not thought to affect general circadian behaviour but it evokes an increased behavioural response to light in the suprachiasmatic nucleus, in conjunction with increased Per1 gene expression ([88–90], Figure 4).…”