A method for constructing retinal hemangioma-like hyperplasia and/or retinal capillary hemangioma model

Abstract

The invention discloses a mouse model of retinal hemangioma-like hyperplasia and / or retinal capillary hemangioma, which is a gene knockout mouse obtained by crossing Cre mice, Rb floxed mice and Vhl floxed mice. There are a large number of new blood vessels in the peripheral retina of the Rb / Vhl double knockout mouse model of the present invention, and these blood vessels penetrate the whole layer to form a dense capillary network, and lose the normal layered structure of the three-layer retinal vascular network. These phenotypes are more severe than the retinal neovascularization in the state-of-the-art RAP model; Rb / P107 / Vhl TKO mice still exhibit some neovascularization in the peripheral retina, but develop distinct stage III RAP and RCH-like lesions in the subretina .

Description

technical field [0001] The invention specifically relates to a method for constructing a model of retinal hemangioma-like hyperplasia and / or retinal capillary hemangioma. Background technique [0002] Retinal vascular disease is the most common fundus disease. Due to the unclear pathogenesis, it has always been the focus and difficulty of ophthalmology clinical work. Retinal angiomatous proliferation (RAP) and retinal capillary hemangioma (RCH) are important representatives of such diseases. Clinically, RAP is divided into three stages, including intraretinal neovascularization (stage I), subretinal neovascularization (stage II) and choroidal neovascularization (stage III). Pathologically, advanced RAP showed hemangioma-like growth, similar to RCH. [0003] RAP and RCH occur in the elderly and young adults respectively, and are very similar in pathology. The main feature is that the "tumor body" is mainly composed of vascular endothelial cells and foamy stromal cells, and ...

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Problems solved by technology

[0005] Regarding the RCH model, since human RCH is caused by mutations in the VHL gene, Haase et al. constructed Vhl gene knockout mice in 2001 and found that Vhl- / - mice died at the embryonic stage, while Vhl+ / - mice had no RCH or Central nervous system hemangioma (Haase et al., 2001); after 2010, a variety of retinal-specific Vhl gene knockout mice were constructed, but none of them had RCH formation, but retinal vascular development was found to be delayed (Arreola et al. ,2018; Barben et al.,2018; Kurihara et al.,2010; Lange et al.,2011; Usui et al.,2015)

In 2018, Wang et al. (Wang et al., 2018) knocked out the Vhl gene in angioblasts and found that it could lead to lesions similar to early RCH, including retinal vascular dilation and vascular leakage, but no hemangioma was found in pathological examination retinal neovascularization

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