Construction method of retinal angiomatous proliferation (RAP) and/or retinal capillary hemangioma (RCH) model

Abstract

The invention discloses a retinal angiomatous proliferation (RAP) and / or retinal capillary hemangioma (RCH) mouse model; the model is a gene knockout mouse obtained by crossing a Cre mouse, a Rb floxed mouse and a Vhl floxed mouse.A large number of new blood vessels exist on the peripheral retina of an Rb / Vhl double knockout (DKO) mouse model, the blood vessels penetrate an entire layer, and a dense capillary network is formed and the normal layered structure of a retinal three-layer capillary network is lost.The phenotypes are more severe than the retinal neovascularization in an RAP model inthe prior art; some new blood vessels still exist on the peripheral retina of Rb / P107 / Vhl triple knockout (TKO) mice, but significant phase III RAP and RCH lesions are formed under the retina.

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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