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Restoration of visual performance by d-serine in models of inner and outer retinal dysfunction assessed using sweep VEP measurements in the conscious rat and rabbit.

Abstract：

:The NMDA subtype of glutamate receptor and its co-agonist d-serine play a key role in synaptic function in the central nervous system (CNS), including visual cortex and retina. In retinal diseases such as glaucoma and macular degeneration, a loss of vision arises from malfunction of retinal cells, resulting in a glutamate hypofunctional state along the visual pathway in the affected parts of the visual field. An effective strategy to remedy this loss of function might be to increase extracellular levels of d-serine and thereby boost synaptic NMDA receptor-mediated visual transmission and/or plasticity to compensate for the impairment. We tested this idea in brain slices of visual cortex exhibiting long-term potentiation, and in rodent models of visual dysfunction caused by retinal insults at a time when the injury had stabilized to look for neuroenhancement effects. An essential aspect of the in vivo studies involved adapting sweep VEP technology to conscious rats and rabbits and combining it with intracortical recording while the animals were actively attending to visual information. Using this technology allowed us to establish complete contrast sensitivity function curves. We found that systemic d-serine dose-dependently rescued the contrast sensitivity impairment in rats with blue light-induced visual dysfunction. In rabbits with inner retinal dysfunction, both systemic and intravitreal routes of d-serine provided a rescue of visual function. In sum, we show that co-agonist stimulation of the NMDA receptor via administration of exogenous d-serine might be an effective therapeutic strategy to enhance visual performance and compensate for the loss of vision resulting from retinal disease.

journal_name

Vision Res

journal_title

Vision research

authors

Staubli U,Rangel-Diaz N,Alcantara M,Li YX,Yang JY,Zhang KM,Foster AC

doi

10.1016/j.visres.2016.07.005

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

35-48

eissn

0042-6989

issn

1878-5646

pii

S0042-6989(16)30078-5

journal_volume

127

pub_type

杂志文章

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Restoration of visual performance by d-serine in models of inner and outer retinal dysfunction assessed using sweep VEP measurements in the conscious rat and rabbit.