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Repeat Corneal Neovascularization is Characterized by More Aggressive Inflammation and Vessel Invasion Than in the Initial Phase
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.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Missouri, MO USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Chonbuk Natl Univ, South Korea.
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2019 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, no 8, p. 2990-3001Article in journal (Refereed) Published
Abstract [en]

Purpose: Treatment of corneal neovascularization can lead to vessel regression and recovery of corneal transparency. Here, we examined the response of the cornea to a repeated stimulus after initial vessel regression comparing the second wave of neovascularization with the first.

Methods: Corneal neovascularization was induced by surgical suture placement in the rat cornea for 7 days, followed by suture removal and a 30-day regression period. Corneas were then re-sutured and examined for an additional 4 days. Longitudinal slit-lamp imaging, in vivo confocal microscopy, and microarray analysis of global gene expression was conducted to assess the inflammatory and neovascularization response. Inhibitory effect of topical dexamethasone for repeat neovascularization was assessed.

Results: After initial robust neovascularization, 30 days of regression resulted in the recovery of corneal transparency; however, a population of barely functional persistent vessels remained at the microscopic level. Upon re-stimulation, inflammatory cell invasion, persistent vessel dilation, vascular invasion, and gene expression of VegfaIl1βIl6Ccl2Ccl3, and Cxcl2 all doubled relative to initial neovascularization. Repeat neovascularization occurred twice as rapidly as initially, with activation of nitric oxide and reactive oxygen species, matrix metalloproteinase, and leukocyte extravasation signaling pathways, and suppression of anti-inflammatory LXR/RXR signaling. While inhibiting initial neovascularization, a similar treatment course of dexamethasone did not suppress repeat neovascularization.

Conclusions: Persistent vessels remaining after the initial resolution of neovascularization can rapidly reactivate to facilitate more aggressive inflammation and repeat neovascularization, highlighting the importance of achieving and confirming complete vessel regression after an initial episode of corneal neovascularization.

Place, publisher, year, edition, pages
Rockville, MD, United States: Association for Research in Vision and Ophthalmology , 2019. Vol. 60, no 8, p. 2990-3001
Keywords [en]
corneal neovascularization; neovascularization; cornea; angiogenesis; inflammation
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-159266DOI: 10.1167/iovs.19-27591ISI: 000476597500005PubMedID: 31310656Scopus ID: 2-s2.0-85070020941OAI: oai:DiVA.org:liu-159266DiVA, id: diva2:1341154
Note

Funding Agencies|Swedish Research Council (Stockholm, Sweden) [2012-2472]

Available from: 2019-08-07 Created: 2019-08-07 Last updated: 2019-11-15Bibliographically approved

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Mukwaya, AnthonnyMirabelli, PierfrancescoLennikov, AntonThangavelu, MuthukumarJensen, LassePeebo, BeatriceLagali, Neil
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Ophthalmology in LinköpingDivision of Cardiovascular MedicineDepartment of Clinical Pharmacology
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