Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization

Abstract

Type 3 macular neovascularization (MNV3), or retinal angiomatous proliferation (RAP), is a distinct type of neovascular age-related macular degeneration (AMD), which is a leading cause of vision loss in older persons. During the past decade, systematic investigation into the clinical, multimodal imaging, and histopathological features and therapeutic outcomes has provided important new insight into this disease. These studies favor the retinal origin of MNV3 and suggest the involvement of retinal hypoxia, inflammation, von Hippel–Lindau (VHL)–hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) pathway, and multiple cell types in the development and progression of MNV3. Several mouse models, including the recently built Rb/p107/Vhl triple knockout mouse model by our group, have induced many of the histological features of MNV3 and provided much insight into the underlying pathological mechanisms. These models have revealed the roles of retinal hypoxia, inflammation, lipid metabolism, VHL/HIF pathway, and retinoblastoma tumor suppressor (Rb)–E2F cell cycle pathway in the development of MNV3. This article will summarize the clinical, multimodal imaging, and pathological features of MNV3 and the diversity of animal models that exist for MNV3, as well as their strengths and limitations.

Identification of Novel Pathways Regulated by APE1/Ref-1 in Human Retinal Endothelial Cells

“…The APEX1 KD effects in selected cancer cells were evaluated differently depending on the data resources, qualities, and processing methods. (1) The MPNST (malignant peripheral nerve sheath tumor) cell line NF90-8 was received from Dr. Verena Staedtke (Johns Hopkins University), and APEX1 KD was performed in NF90-8 cells as previously reported [37]. The RNA-seq analysis was conducted in the same manner as for APEX1 KD in HRECs.…”

“…Aberrant neovascularization (NV) is a hallmark of major, blinding ocular diseases including neovascular “wet” age-related macular degeneration (nAMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP) [ 1 ]. Collectively, these diseases are major causes of visual impairment [ 2 ].…”

“…A key feature of nAMD is choroidal neovascularization (CNV), the growth of blood vessels into the subretinal space in the macular area, while ROP and PDR are associated with NV from the retinal vasculature [ 1 , 4 ]. CNV damages central vision, causing blurred vision and blind spots.…”

A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction

“…Idiopathic retinal telangiectasia with exudation [78], a spectrum of unilateral, sporadic disease phenotypes that includes forms of Coats disease, is characterized by capillary networks, which emanate from the deep retinal plexus, and exudative retinal detachment. A form of age-related macular degeneration, macular neovascularization Type 3 (MNV3), also called retinal angiomatous proliferation (RAP), consists of neovessels that originate from the deep retinal plexus and in late stages anastomose with the choroidal circulation [79,80]. Macular telangiectasia type 2 [81] is a bilateral neovascular disease presenting simultaneously with local retinal detachment in the form of subfoveal fluid accumulation in 1-2% of affected patients [82,83].…”

“…Macular telangiectasia type 2 [81] is a bilateral neovascular disease presenting simultaneously with local retinal detachment in the form of subfoveal fluid accumulation in 1-2% of affected patients [82,83]. These diseases are associated with photoreceptor loss [78][79][80][81]. Thus, tvrm77 mice may recapitulate aspects of retinal neovascularization and degeneration as observed in these diseases.…”