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A microarray whole-genome gene expression dataset in a rat model of inflammatory corneal angiogenesis
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Stockholm University, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.ORCID iD: 0000-0001-8722-9155
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
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2016 (English)In: Scientific Data, E-ISSN 2052-4463, Vol. 3, article id UNSP 160103Article in journal (Refereed) Published
Abstract [en]

In angiogenesis with concurrent inflammation, many pathways are activated, some linked to VEGF and others largely VEGF-independent. Pathways involving inflammatory mediators, chemokines, and micro-RNAs may play important roles in maintaining a pro-angiogenic environment or mediating angiogenic regression. Here, we describe a gene expression dataset to facilitate exploration of pro-angiogenic, pro-inflammatory, and remodelling/normalization-associated genes during both an active capillary sprouting phase, and in the restoration of an avascular phenotype. The dataset was generated by microarray analysis of the whole transcriptome in a rat model of suture-induced inflammatory corneal neovascularisation. Regions of active capillary sprout growth or regression in the cornea were harvested and total RNA extracted from four biological replicates per group. High quality RNA was obtained for gene expression analysis using microarrays. Fold change of selected genes was validated by qPCR, and protein expression was evaluated by immunohistochemistry. We provide a gene expression dataset that may be re-used to investigate corneal neovascularisation, and may also have implications in other contexts of inflammation-mediated angiogenesis.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 3, article id UNSP 160103
National Category
Oceanography, Hydrology and Water Resources
Identifiers
URN: urn:nbn:se:liu:diva-133892DOI: 10.1038/sdata.2016.103ISI: 000390238000001PubMedID: 27874850OAI: oai:DiVA.org:liu-133892DiVA, id: diva2:1065074
Note

Funding Agencies|Swedish Research Council [2012-2472]; Bayer HealthCare AB, Solna, Sweden; Bioinformatics Infrastructure for Life Sciences (BILS) Sweden

The publication is a peer-reviewed description of a research dataset. Aims and scope of the journal:Scientific Data primarily publishes Data Descriptors, a new type of publication that provides detailed descriptions of research datasets, including the methods used to collect the data and technical analyses supporting the quality of the measurements. Data Descriptors focus on helping others reuse data, rather than testing hypotheses, or presenting new interpretations, methods or in-depth analyses.

Available from: 2017-01-13 Created: 2017-01-13 Last updated: 2018-05-21
In thesis
1. Regulation of inflammation and angiogenesis in the cornea
Open this publication in new window or tab >>Regulation of inflammation and angiogenesis in the cornea
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammation and angiogenesis, the growth of new blood vessels from pre-existing ones, are involved in tumor growth, ocular diseases and wound healing. In ocular angiogenesis, new pathological vessels grow into a specific eye tissue, leak fluid, and disrupt vision. The development of safe and effective therapies for ocular angiogenesis is of great importance for preventing blindness, given that current treatments have limited efficacy or are associated with undesirable side effects. The search for alternative treatment targets requires a deeper understanding of inflammation and how it can lead to angiogenesis in the eye in pathologic situations. This thesis provides new insights into the regulation of inflammation and angiogenesis, particularly at the gene expression and phenotypic levels, in different situations characterized by angiogenesis of the cornea, often called corneal neovascularization. For instance, specific genes and pathways are either endogenously activated or suppressed during active inflammation, wound healing, and during resolution of inflammation and angiogenesis, serving as potential targets to modulate the inflammatory and angiogenic response. In addition, as part of the healing response to restore corneal transparency, inflammation and angiogenesis subside with time in the cornea. In this context, LXR/RXR signaling was found to be activated in a time-dependent manner, to potentially regulate resolution of inflammation and angiogenesis. During regression of new angiogenic capillaries, ghost vessels and empty basement membrane sleeves are formed, which can persist in the cornea for a long time. Here, ghost vessels were found to facilitate subsequent revascularization of the cornea, while empty basement membrane sleeves did not revascularize. The revascularization response observed here was characterised by vasodilation, increased inflammatory cell infiltration and by sprouting at the front of the reperfused vessels. Importantly, reactive oxygen species and nitrous oxide signaling among other pro-inflammatory pathways were activated, and at the same time anti-inflammatory LXR/RXR signaling was inhibited. The interplay between activation and inhibition of these pathways highlights potential mechanisms that regulate corneal revascularization. When treating corneal neovascularization clinically, corticosteroids are in widespread use due to their effectiveness. To minimize the many undesirable side effects associated with corticosteroid use, however, identifying new and more selective agents is of great importance. Here, it was observed that corticosteroids not only suppressed pro-inflammatory chemokines and cytokines, but also activated the classical complement pathway. Classical complement may represent a candidate for further selective therapeutic manipulation to investigate its effect on treatment of corneal neovascularization.

In summary, this thesis identifies genes, pathways, and phenotypic responses involved in sprouting and remodeling of corneal capillaries, highlights novel pathways and factors that may regulate inflammation and angiogenesis in the cornea, and provides insights into regulation of capillary regression and reactivation. Further investigation of these regulatory mechanisms may offer alternative and effective treatment targets for the treatment of corneal inflammation and angiogenesis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 55
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1625
National Category
Ophthalmology Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-147979 (URN)10.3384/diss.diva-147979 (DOI)9789176852842 (ISBN)
Public defence
2018-06-01, Nils-Holger salen, Campus US, Linköping, 13:06 (English)
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Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2018-05-21Bibliographically approved

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Mukwaya, AnthonyXeroudaki, MariaPeebo, BeatriceAli, ZaheerLennikov, AntonJensen, LasseLagali, Neil
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