Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia?
Recent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus mu...
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PeerJ Inc.
2017-12-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/4214.pdf |
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| author | Andrea B. Agarwal Austin J. Christensen Cheng-Yuan Feng Dan Wen L. Alan Johnson Christopher S. von Bartheld |
| author_facet | Andrea B. Agarwal Austin J. Christensen Cheng-Yuan Feng Dan Wen L. Alan Johnson Christopher S. von Bartheld |
| author_sort | Andrea B. Agarwal |
| collection | DOAJ |
| description | Recent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus muscles may explain the specific association of schizophrenia with exotropia but not esotropia. Samples from horizontal extraocular muscles were obtained during strabismus surgery and compared with age- and muscle type-matched normal muscles from organ donors. We used PCR arrays to identify differences in gene expression among 417 signaling molecules. We then focused on established schizophrenia-related growth factors, cytokines, and regulators of the extracellular matrix. Among 36 genes with significantly altered gene expression in dysfunctional horizontal rectus muscles, over one third were schizophrenia-related: CTGF, CXCR4, IL1B, IL10RA, MIF, MMP2, NPY1R, NRG1, NTRK2, SERPINA3, TIMP1, TIMP2, and TNF (adjusted p value ≤ 0.016667). By PCR array, expression of three of these genes was significantly different in medial rectus muscles, while eleven were significantly altered in lateral rectus muscles. Comparing baseline levels between muscle types, three schizophrenia-related genes (NPY1R, NTRK2, TIMP2) had lower levels of expression in medial rectus muscles. Despite the surprisingly large number of schizophrenia-related genes with altered gene expression levels in dysfunctional muscles, the lack of specificity for medial rectus muscles undermines a model of shared, region-specific gene expression abnormalities between exotropia and schizophrenia, but rather suggests consideration of the alternative model: that exotropia-induced aberrant early visual experiences may enable and/or contribute as a causative factor to the development of schizophrenia. |
| first_indexed | 2024-03-09T08:06:14Z |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:06:14Z |
| publishDate | 2017-12-01 |
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| spelling | doaj.art-2893f43b72bc4039b7d380095769fcbf2023-12-02T23:48:35ZengPeerJ Inc.PeerJ2167-83592017-12-015e421410.7717/peerj.4214Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia?Andrea B. Agarwal0Austin J. Christensen1Cheng-Yuan Feng2Dan Wen3L. Alan Johnson4Christopher S. von Bartheld5Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USADepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USADepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USADepartment of Ophthalmology, Xiangya Hospital, Central South University, Changsha, ChinaSierra Eye Associates, Reno, NV, USADepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USARecent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus muscles may explain the specific association of schizophrenia with exotropia but not esotropia. Samples from horizontal extraocular muscles were obtained during strabismus surgery and compared with age- and muscle type-matched normal muscles from organ donors. We used PCR arrays to identify differences in gene expression among 417 signaling molecules. We then focused on established schizophrenia-related growth factors, cytokines, and regulators of the extracellular matrix. Among 36 genes with significantly altered gene expression in dysfunctional horizontal rectus muscles, over one third were schizophrenia-related: CTGF, CXCR4, IL1B, IL10RA, MIF, MMP2, NPY1R, NRG1, NTRK2, SERPINA3, TIMP1, TIMP2, and TNF (adjusted p value ≤ 0.016667). By PCR array, expression of three of these genes was significantly different in medial rectus muscles, while eleven were significantly altered in lateral rectus muscles. Comparing baseline levels between muscle types, three schizophrenia-related genes (NPY1R, NTRK2, TIMP2) had lower levels of expression in medial rectus muscles. Despite the surprisingly large number of schizophrenia-related genes with altered gene expression levels in dysfunctional muscles, the lack of specificity for medial rectus muscles undermines a model of shared, region-specific gene expression abnormalities between exotropia and schizophrenia, but rather suggests consideration of the alternative model: that exotropia-induced aberrant early visual experiences may enable and/or contribute as a causative factor to the development of schizophrenia.https://peerj.com/articles/4214.pdfStrabismusGene expressionPCR ArrayGrowth factorExtraocular muscleBiomarker |
| spellingShingle | Andrea B. Agarwal Austin J. Christensen Cheng-Yuan Feng Dan Wen L. Alan Johnson Christopher S. von Bartheld Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? PeerJ Strabismus Gene expression PCR Array Growth factor Extraocular muscle Biomarker |
| title | Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? |
| title_full | Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? |
| title_fullStr | Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? |
| title_full_unstemmed | Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? |
| title_short | Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia? |
| title_sort | expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus an explanation for the link between exotropia and schizophrenia |
| topic | Strabismus Gene expression PCR Array Growth factor Extraocular muscle Biomarker |
| url | https://peerj.com/articles/4214.pdf |
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