Immunoreactivity of Ecel 1 GFAP and ATF3 in retinal sections.

<p><b>(</b>A) Endothelin converting enzyme-like 1 (Ecel1), (B) Glial fibrillary acidic protein (GFAP) and (C) Activating transcription factor-3 (ATF3); representative images shown for dorsal and ventral retina. Semi-quantification of immunointensity was performed on the retinal ganglion cell layer (GCL) in dorsal, central and ventral retina on normal uninjured animals and the retina of animals at 1 and 7 days following PT. Error bars show the standard error of the mean (SEM) for each experiment. Statistically analysis conducted on each region and significant differences between retinal tissue of injured and uninjured ON are indicated by <i>asterisks</i> (* p-value < 0.05, ** p-value < 0.01, *** p-value <0.001). Scale bar = 10 μm.</p

GSEA of differentially expressed genes (FC > 1.4, p-value < 0.05) between dorsal and ventral retina, showing GO classified biological_functions at day 1 and day 7 after PT injury.

<p>All biological_function clusters are upregulated in dorsal retina when compared to ventral retina. Top 10 significant (p-value < 0.05) biological_functions shown for day 1 with a list of contributing genes that are differentially expressed by fold change > 2, p-value < 0.05. Only 2 clusters were enriched from differentially expressed genes between dorsal and ventral retina at day 7 after injury. The genes listed are differentially expressed by a FC > 1.5. The bar graph depicts the total number of genes that contribute to each functional cluster.</p

Downregulated genes in dorsal and ventral retina following a PT injury.

<p>Fold changes comparing injured retina to region matched normal controls.</p

Schematic diagram of dissection of retina for microarray studies.

<p>RGC somata whose axons are transected after PT of the optic nerve are located in the dorsal, temporal and central areas (indicated in blue), leaving RGCs in nasal and ventral retina initially intact but vulnerable to secondary degeneration[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192348#pone.0192348.ref026" target="_blank">26</a>]. The dashed line indicates where dorsal and ventral retinal tissue were separated.</p

GSEA analysis was performed on a list of significantly differentially expressed genes using a cut off ≥ 1.4 fold change and p-value ≤ 0.05.

<p>Pie charts show numbers of genes from experimental data present in each functional category listed in the legend. The order of listing of functional groups is determined by the number of genes present in each category. Hit obtained from <i>Gene Ontology (GO) categories</i>: <i>‘molecular_function’</i>, <i>‘cellular_component’ ‘biological_process’ and ‘Pathway studio ontology’</i> (A) Enriched functional groups in dorsal retina 1 day following PT injury compared to dorsal uninjured retina yielded significant differences in 88 functional groups. The top 10 functional groups listed based on number of genes present in each functional group (B). Enriched functional groups between dorsal retina 7 days following PT injury and dorsal uninjured retina yielded 67 significant functional groups. (C) Enriched functional groups in ventral retina 1 day following PT injury compared to ventral uninjured retina: only 2 significant functional groups were enriched. (D) Enriched functional groups in ventral retina 7 days following PT injury compared to ventral uninjured retina yielded 7 significant functional groups.</p

Upregulated genes in dorsal and ventral retina following a PT injury.

<p>Fold changes comparing injured retina to region matched normal controls.</p

Discriminant analysis on biological clusters related to oxidation-reduction, immune response and apoptosis after partial optic nerve injury.

<p>Discriminant analysis on biological clusters related to oxidation-reduction, immune response and apoptosis after partial optic nerve injury.</p

Significantly altered pathway categories in PE decidual transcriptome (p < 0.001).

<p>^a Presented as range where appropriate to reflect the spread of individual p-values of each Gene Ontology (GO) set from each transcriptome profiling batch.</p><p>Significantly altered pathway categories in PE decidual transcriptome (p < 0.001).</p

Summary of patient characteristics.

<p>NA, not applicable.</p><p>^a Shown is the mean ± SEM unless stated otherwise.</p><p>^b Student’s <i>t</i> test with Welch’s Correction for parametric data and 2 × 2 contingency table with Fisher’s Exact Test for categorical data were used.</p><p>^c One PE patient had a twin pregnancy.</p><p>^d Data shown as median.</p><p>Summary of patient characteristics.</p

Downstream genes of identified regulators and targets of maternal PE susceptibility genes.

<p>A gene network of downstream targets of identified regulators/targets of maternal PE susceptibility genes was generated with Pathway Studio 9.0. Each link is supported by at least one published reference. Connecting genes are coloured in yellow, regulator/target genes of maternal PE susceptibility genes in red and major downstream targets of these genes in purple.</p