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Anthony Mukwaya, Maria Xeroudaki, Anton Lennikov, Beatrice Peebo, Lasse Jensen, Neil S Lagali; Cornea re-vascularisation response after initial vascular regression. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1004.
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Cessation of anti-VEGF therapy can lead to vessel regrowth. In the cornea, regression of vessels can lead to the appearance of ghost vessels which can persist for a long time. However, little is known about the role played by these ghost vessels in the event of a second corneal neovascularisation. Here, we aimed to investigate the role of ghost vessels in re-vascularisation of the cornea in a rat model of angiogenesis.
Male Wistar rats were sutured temporally in the cornea at 1.5mm from the limbus on day 0. On day 7, the vascularized area of the cornea was imaged in vivo, followed by suture removal to induce capillary regression over a period of four weeks. At four weeks, the cornea was re-sutured. At 24h, 72h, and 96h after re-suturing, in vivo imaging was performed, and corneal tissue was harvested for immunohistochemical analysis and global gene expression analysis (at 24h) using microarrays.
Empty basement membrane sleeves were not rapidly re-functionalized upon re-suturing. Instead, ghost vessels, which were severely narrowed but with detectable flow, underwent a rapid and powerful dilation phenomenon from 24h to 96h. This was accompanied by rapid blood flow, and infiltration of inflammatory cells. Several days post-dilation, new sprouting from dilated ghost vessels was observed.
Corneal revascularisation occurs via rapid re-perfusion and hyper-dilation of pre-existing persistent ghost vessels. Previously abandoned empty basement membrane sleeves do not re-perfuse; instead, new sprouts originate from hyper-dilated ghost vessels. This highlights the importance of targeting persistent ghost vessels in an otherwise regressed vascular bed.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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