Bryan W Jones’s scientific contributions

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Publications (1)

Fig. 1. Metabolic signatures with aging. A: Whole retina samples of non-injured retina from 3-and 12 months of age mice underwent metabolic profiling. A total of 100 metabolites were identified. Volcano plot indicating the number and the increase/decrease of significantly changed metabolites in 12 months of age non-injured retinae in comparison to 3 months of age non-injured retinae (p-value < 0.05, red = increased, blue = decreased). Of the 100 measured metabolites 14 were increased and 3 were decreased in retina from 12 months of age mice in comparison to retina from 3 months of age animals. N = 8 mice/group. B: Summary Plot for Kyoto Encyclopedia of Genes and Genomes (KEGG) Over Representation Analysis (ORA) metabolites demonstrates significant pathway enrichment of pathways related to Lysine degradation and valine, leucine and isoleucine degradation and biosynthesis C: The calculated exploratory Receiver Operating Characteristic Curve (ROC) calculated with 10 features (model 3) shows high specificity and sensitivity of the measured metabolites with aging (Area under the curve = 0.987). The 95 percent confidence interval is shown as a band around the ROC curve. D: Plot of predicted class probabilities for all samples using a single biomarker model. The classification boundary is at the center (x = 0.5, dotted line). E Plot of the most important features of a selected model ranked from most to least important. 2 of the most relevant metabolites discriminating between old and young are relevant for intraretinal synaptic signaling.
Fig. 2. Metabolic signatures in retina of 3 months of age mice after IOP injury. A: The calculated principal component analysis (PCA) shows good discrimination between injured and non-injured retina in the 3 months of age animals (squares represent the injured 3-months of age retina, dots represent the non-injured 3 months of age retina). N = 8 mice/group. B: The calculated exploratory Receiver Operating Characteristic Curve (ROC) calculated with 10 features (model 3) shows high specificity and sensitivity of the measured retinal metabolites with injury in 3 months of age mice (Area under the curve = 1). The 95 percent confidence interval is shown as a band around the ROC curve. C: Whole retina samples of injured (single IOP challenge) and non-injured retina from 3 months of age mice underwent metabolic profiling. Of the total of 100 identified metabolites, 18 were up-regulated and 18 were down-regulated in retinae of young animals 3 days after a single IOP elevation injury, as demonstrated in the volcano plot (FDR < 0.05, red = increased, blue = decreased). D: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of metabolites demonstrates significant pathway enrichment of pathways related to neurotransmission such as Arginine and proline metabolism, Glycine, serine and threonine metabolism and Alanine, aspartate and glutamate metabolism. Another enriched pathway is the taurine and hypotaurine metabolism. E: Plot of the most important features of a selected model (Model 3) ranked from most to least important. Guanidoacetic acid is one main metabolite in this model to discriminate between injured and uninjured retina and is increased in injured retina after IOP a single IOP in 3 months of age animals.
Fig. 3. Metabolic signatures in retina of 12 months of age mice after IOP injury. A: The calculated principal component analysis (PCA) fails to demonstrate discrimination between injured and non-injured retina in the 12 months of age animals (squares represent the injured 12 months of age retina, dots represent the noninjured 12 months of age retina). N = 8 mice/group. B: The calculated exploratory Receiver Operating Characteristic Curve (ROC) calculated with 10 features (model 3) shows lower specificity and sensitivity of the measured metabolites in 12 months of age retina after IOP elevation injury (Area under the curve = 0.811). The 95 percent confidence interval is shown as a band around the ROC curve. C: Whole retina samples of injured (single IOP challenge) and non-injured retina from 12 months of age mice underwent metabolic profiling. Of the total of 100 identified metabolites, 8 were up-regulated and 11 were down-regulated in retinae of old animals 3 days after a single IOP elevation injury, as demonstrated in the volcano plot (FDR < 0.05, red = increased, blue = decreased). D: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of metabolites demonstrates significant pathway enrichment related to neurotransmission and pathways related to Phenylalanine, tyrosine and tryptophan biosynthesis as well as taurine and hypotaurine metabolism. E Plot of the most important features of a selected model (Model 3) ranked from most to least important.
Fig. 4. Comparison of injury response in both young and middle-aged mice. A: 36 metabolites were significantly differently regulated in the retina of 3 months of age (young) mice after injury in comparison to the non-injured 3 months of age retina, whereas 19 metabolites were significantly differently regulated in the 12 months of age (old) injured retina in comparison to the 12 months of age non-injured control. Of these metabolites, 13 metabolites were found to be differently regulated in both the old and the young retina after injury. All these metabolites showed the same mode of change (increased or decreased levels) in the 12 months of age (black) and the 3 months of age (orange) retina after a single short term IOP elevation injury. N = 8 mice/group. B shows the signal intensity of GABA and Taurine, which are both found in significantly lower levels after IOP injury in the retina of 3 months of age and 12 months of age mice Violin plots show the non-normalized signal intensities. The black bar shows the median, the dotted lines show the 1st and the 3rd quartile. C shows localization of GABA immunoreactivity within the retina. CRALBP staining (green) highlights especially Mueller cells and the retinal pigment epithelium and allows to identify the different retinal layers. GABA immunoreactivity (purple) is seen in the IPL, INL and RGC layer. Exemplary grey scale images of GABA immunoreactivity in the CTRL and at Day 3 after IOP elevation are shown on the right. Arrows with small arrowheads point towards GABA-hi cells and arrows with large arrowheads point towards GABA-lo cells. Scale bar represents182µm D shows the GABA-hi and the GABA-lo cell numbers/182µm in the CTRL and Day-3 post-IOP elevation retina (D3) (* p < 0.05). N = 3 mice/group. E Example traces of eIPSC recordings from 3 months of age mice. eIPSC traces from uninjured controls and 3-days post IOP elevation. Scale = 200 ms x 100 pA. Quantification of the eIPSC amplitude demonstrates a significant reduction in IPSC amplitude 3-days post IOP elevation compared to controls (* p < 0.05). F Quantification of the eIPSC decay time demonstrates a significantly faster IPSC decay 3-days post IOP elevation compared to controls (* p < 0.05). G Example traces of spontaneous IPSC recordings from retinal ganglion cells in 3 months of age mice. sIPSCs were recorded 3-days post IOP elevation as well as from uninjured controls. Scale = 10 ms x 100 pA. Quantification of sIPSC amplitude demonstrates no significant change following IOP elevation (p > 0.05). Quantification of sIPSC frequency demonstrates a significant decrease in IPSC frequency 3-days post IOP elevation compared to controls (** p < 0.01). N = 4-6 mice/group.
Excitatory and inhibitory neurotransmitter alterations with advancing age and injury in the mouse retina
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March 2025

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Neurobiology of Aging

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Vicki Chrysostomou

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Markus Karlsson

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Jonathan G Crowston
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