Regulatory effects of inhibiting the activation of glial cells on retinal synaptic plasticity

Abstract

Various retinal injuries induced by ocular hypertension have been shown to induce plastic changes in retinal synapses, but the potential regulatory mechanism of synaptic plasticity after retinal injury was still unclear. A rat model of acute ocular hypertension was established by injecting saline intravitreally for an hour, and elevating the intraocular pressure to 14.63 kPa (110 mmHg). Western blot assay and immunofluorescence results showed that synaptophysin expression had a distinct spatiotemporal change that increased in the inner plexiform layer within 1 day and spread across the outer plexiform layer after 3 days. Glial fibrillary acidic protein expression in retinae was greatly increased after 3 days, and reached a peak at 7 days, which was also consistent with the peak time of synaptophysin expression in the outer plexiform layer following the increased intraocular pressure. Fluorocitrate, a glial metabolic inhibitor, was intravitreally injected to inhibit glial cell activation following high intraocular pressure. This significantly inhibited the enhanced glial fibrillary acidic protein expression induced by high intraocular pressure injury. Synaptophysin expression also decreased in the inner plexiform layer within a day and the widened distribution in the outer plexiform layer had disappeared by 3 days. The results suggested that retinal glial cell activation might play an important role in the process of retinal synaptic plasticity induced by acute high intraocular pressure through affecting the expression and distribution of synaptic functional proteins, such as synaptophysin.

Knocking down of heat-shock protein 27 directs differentiation of functional glutamatergic neurons from placenta-derived multipotent cells

“…The number and distribution of excitatory glutamatergic and inhibitory gamma-aminobutyric acid (GABAergic) neurons in the human central nervous system must be precisely controlled. The imbalance or loss of glutamatergic and GABAergic neurons is observed in many nervous system disorders, such as Alzheimer’s disease 11 , age-related macular degeneration 12 and mental retardation 13 . Although Alzheimer’s disease affects many types of neurons, including non-glutamatergic interneurons and cholinergic projection neurons, as well as glia, it is still desirable to understand the molecular mechanisms that govern glutamatergic neuron differentiation and to develop a consistent and reproducible glutamatergic neuron source for elucidating the aetiology of neurological disorders.…”

Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure

“…In the current study, we observed the upregulation of presynaptic proteins without the accompanying changes in postsynaptic proteins in primary mixed cultures exposed to EHP for 2 h. That means that EHP only induced presynaptic protein changes, but no intact and functional synapses were formed[ 13 , 22 ]. However, protein synthesis function is highly dependent on mitochondrial energy production, and abnormal synthesis function may lead to energy deficits in cells and increased apoptosis[ 52 ].…”

“…In many neuropathic and nervous injury states, glia cells can be activated, characterized by increased proliferation and glial fibrillary acidic protein (GFAP) expression[ 20 , 21 ]. Our previous study also demonstrated that retinal synaptic changes are accompanied by activation of macroglia cells (astrocytes and Müller cells) following acute elevated IOP[ 22 ]. Meanwhile, the already increased expression of SYN was decreased when the activated macroglia cells were inhibited by fluorocitrate.…”

Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

“… Porciatti and Ventura (2012) used the concept of neural plasticity to simulate the reversible/inducible changes in the PERG during the critical period (stage of retinal ganglion cell dysfunction), which precedes their death. Zhou et al (2014) suggested that retinal glial cell activation induced by acute high intraocular pressure may cause the process of retinal synaptic plasticity through affecting the expression of synaptophysin and other synaptic proteins. In the rat model of acute ocular hypertension, the increase in expression of synaptophysin across the retina was observed from the inner to the outer plexiform layer.…”