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T.D. Kimble, A.J. Reiner; Glutamine Synthetase is Increased in Retinal Muller Cells after Central Lesions that Disrupt Adaptive Parasympathetic Regulation of Choroidal Blood Flow . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3060.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Choroidal blood flow (ChBF) in pigeons is neurally regulated by a parasympathetic circuit whose preganglionic neurons reside in the nucleus of Edinger-Westphal (EW). EW lesions result in decreased basal ChBF and loss of adaptive ChBF control, which has adverse effects on the retina manifested as Müller cell GFAP upregulation, photoreceptor loss and acuity declines. The basis of the retinal injury ensuing from an EW lesion is uncertain, but seems likely to involve an ischemic process. Ischemic injury to neural tissue is typically associated with increased production of the enzyme glutamine synthetase (GS) in glial cells. This enzyme degrades the neurotransmitter glutamate, which is thought to be excessively released by neurons experiencing ischemia. In the present studies, we sought to determine if EW lesions cause retinal Muller cells in pigeons to upregulate GS, which would indicate that the disruption of ChBF control by such a lesion might be injuring the retina via a glutamate-excitotoxicity mediated ischemic process. Methods: GS immunohistochemistry and densitometry were used to assess changes in GS labeling 3 to 40 weeks after an EW lesion in pigeons. GS labeling through the depth of the retina from the outer to the inner limiting membrane was measured in the superior-temporal regions. For each case, a mean density histogram of GS IHC through the retinal depth was generated using computer-assisted methods. Results: GS is normally present at constitutive levels throughout the retinal depth. After an EW lesion, GS labeling was increased 17-24% above normal throughout the retinal depth and remained elevated after nearly a year post-EW lesion. GS labeling was particularly high, compared to normal, in the in the outer nuclear layer and outer part of the inner nuclear layer. Densitometric analysis of the ONL and INL showed an increase of 10-40% above normal in these layers. Conclusions: Muller cell production of GS is increased after disruption of neurogenic ChBF regulation, suggesting that the retinal injury caused by such disruption might be ischemia and glutamate-mediated. Further, the cells in the ONL and outer INL may be more vulnerable to this stress.
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