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Biomedical subjects

Thomas E Salt

Publications and source records attributed to Thomas E Salt.

6 recordsLinked to original sources
PubMed2006

Functional alignment of feedback effects from visual cortex to thalamus.

Following from the classical work of Hubel and Wiesel, it has been recognized that the orientation and the on- and off-zones of receptive fields of layer 4 simple cells in the visual cortex are linked to the spatial alignment and properties of the cells in the visual thalamus that relay the retinal input. Here we present evidence showing that the orientation and the on- and off-zones of receptive fields of layer 6 simple cells in cat visual cortex that provide feedback to the thalamus are similarly linked to the alignment and properties of the receptive fields of the thalamic cells they contact. However, the pattern of influence linked to on- and off-zones is phase-reversed. This has important functional implications.

Action Potentials↗
PubMed2006

Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo.

PURPOSE: To assess the neuroprotective effects of different glutamate modulation strategies, with a nonselective (MK801) and a selective (ifenprodil) NMDA receptor antagonist and a metabotropic glutamate receptor agonist (mGluR Group II, LY354740), in glaucoma-related in vivo rat models of retinal ganglion cell (RGC) apoptosis. METHODS: RGC apoptosis was induced in Dark Agouti (DA) rats by staurosporine (SSP) treatment. Single agents MK801, ifenprodil, or LY354740, or MK801 and LY354740 combined, were administrated intravitreally at different doses. Eyes were imaged in vivo using a recently established technique and the results confirmed histologically. The most effective combined therapy regimen of MK801 and LY354740 was then assessed in a chronic ocular hypertension (OHT) rat model with application at 0, 1, and 2 weeks after OHT surgery and the effects assessed as described before. RESULTS: All strategies of glutamate modulation reduced SSP-induced-RGC apoptosis compared with the control, in a dose-dependent manner: MK801 (R2= 0.8863), ifenprodil (R2= 0.4587), and LY354740 (R2= 0.9094), with EC50s of 0.074, 0.0138, and 19 nanomoles, respectively. The most effective combination dose of MK801 and LY354740 was 0.06 and 20 nanomoles (P < 0.05), respectively, and the optimal timing of the therapy was 0 weeks after OHT surgery (P < 0.05). CONCLUSIONS: This novel SSP model was validated as a useful tool for screening neuroprotective strategies in vivo. Group II mGluR modulation may be a useful treatment for RGC death. Combination therapy optimized to limit neurotoxic effects of MK801 may be an effective neuroprotective approach in retinal degenerative disease. Furthermore, treatments that minimize secondary RGC degeneration may be most useful in glaucoma.

Animals↗
PubMed2004

Contribution of GABAergic inhibition to synaptic responses and LTD early in postnatal development in the rat superior colliculus.

We studied the development of optic tract evoked field potentials (FP) in the rodent superior colliculus (SC) and the effect of GABA antagonists upon their development and upon induction of long-term depression (LTD). Brain slices were cut from Lister Hooded rats. The optic tract was stimulated while recording from the superficial grey layer. GABAergic inhibition was assessed by adding 100 microm picrotoxin and 3 microm CGP55845 antagonists to block GABA A,B,C receptors. LTD was induced with a 50 Hz, 20 s tetanus. At age P2, the FP consisted only of a presynaptic spike. The GABA antagonists had no effect. By P4, the FP consisted of a presynaptic spike, a longer latency population spike, and a field excitatory postsynaptic potential (fEPSP). The fEPSP was slightly prolonged by the GABA antagonists at this age. By P7-P14, a prominent FP with trailing fEPSP was recorded. The GABA antagonists usually had a large effect, with the fEPSP increasing in both amplitude and duration. A mature FP was usually recorded in P15-P23 slices where the GABA antagonist effect remained substantial. LTD could be induced in 17 of 30 control slices from rats aged P4-P26. The average fEPSP amplitude after tetanus was 77.9% of control. Pre-treatment with GABA antagonists produced a short-term potentiation (average 114.0%), rather than LTD, in 14 of 19 cases. This STP was followed by a more prolonged potentiation in 12 of the 14 cases. We conclude that GABAergic inhibitory circuits mature before eye opening and that GABA contributes to induction of LTD in the developing SC.

Animals↗
PubMed2002

In vitro characterization of a spontaneously immortalized human Müller cell line (MIO-M1).

PURPOSE: To characterize a spontaneously immortalized human Müller cell line and to determine whether it retains the characteristics of primary isolated cells without undergoing differentiation in vitro. METHODS: An immortalized cell line obtained from human retina was investigated for the expression of known markers of Müller cells, including cellular retinaldehyde binding protein (CRALBP), glutamine synthetase, epidermal growth factor receptor (EGF-R), alpha-smooth muscle actin (alpha-SMA), and glial fibrillary acidic protein (GFAP). Also examined were the morphologic features of these cells, by scanning and transmission electron microscopy, and their functional characteristics, by electrogenic responses to glutamate. In addition, comparative studies were made of these cells with primary cultures of freshly isolated human Müller cells. RESULTS: The cells expressed CRALBP, EGF-R, glutamine synthetase, and alpha-SMA, as judged by confocal microscopy and Western blot analysis of cell lysates. Western blot analysis did not detect GFAP in cell lysates, but confocal microscopy showed that occasional cells expressed GFAP after detachment from the monolayer. The morphologic features of the cells examined, as judged by scanning and transmission electron microscopy, resemble those of cells derived from primary cell cultures. They possess villous projections on their apical surfaces and contain loose bundles of microtubules aligned parallel to one another and the long axis of the cell process. Characteristically, they contain abundant deposits of glycogen particles that do not differ from those seen in primary isolated cells. Preliminary recordings with intracellular electrodes revealed that these cells have properties similar to those described for mammalian Müller cells and depolarize in response to L-glutamate without significant change in membrane resistance, consistent with the well-established electrogenic uptake of this amino acid. CONCLUSIONS: A spontaneously immortalized Müller cell line was characterized that retains the characteristics of primary isolated cells in culture. To the authors' knowledge, it constitutes the first human Müller cell line reported in the literature. It has been named MIO-M1 (Moorfields/Institute of Ophthalmology-Müller 1) after the authors' institution. Availability of this human cell line will facilitate studies designed to obtain a better understanding of the role of Müller cells in normal and pathologic conditions.

Actins↗