Background: Type 3 macular neovascularization (MNV3) is an important subtype of neovascular age-related macular degeneration. Previously, we established an advanced MNV3-like mouse model by knocking out the Vhl, Rb1, and p107 genes in the retinal progenitors (Rb1/p107/Vhl TKO model). This study investigates the role of the p107 protein (also called Rb transcriptional corepressor like 1, Rbl1) on retinal blood vessels in the VhlKO retina. Methods: By breeding the retinal-specific alpha-Cre mice with Vhl ^floxed mice and p107 ^-/-mice, we got VhlKO, p107KO, and p107/VhlDKO mice. Whole mount retinal IB4 staining, and fundus fluorescein angiography (FFA) were performed to evaluate the retinal vascular vessels. Immunofluorescence staining studied retinal cell types, cell proliferation, and cell death. RNA sequencing, chromatin immunoprecipitation (CHIP), and dual luciferase reporter assay were also performed to study the retinal transcriptome, the binding of p107 protein to the promoter region of Hif target genes, and the effect of the p107 protein on the transcriptional activity of the Hif target genes. Results: p107/VhlDKO mice have delayed regression of hyaloid vessels, retinal degeneration, and retinal neovascularization. The p107 protein significantly inhibits the Hif pathway activity in VhlKO retinas. It can also bind to the promoter regions and suppress the transcriptional activity of several Hif target genes, including Vegfa, Kdr, and Tek. Conclusions:The p107 protein inhibits angiogenesis in the VhlKO retina, as it can bind and inhibit Hif target genes related to retinal angiogenesis.

Background: Type 3 macular neovascularization (MNV3) is an important subtype of neovascular age-related macular degeneration. Previously, we established an advanced MNV3-like mouse model by knocking out the Vhl, Rb1, and p107 genes in the retinal progenitors (Rb1/p107/Vhl TKO model). This study investigates the role of the p107 protein (also called Rb transcriptional corepressor like 1, Rbl1) on retinal blood vessels in the VhlKO retina. Methods: By breeding the retinal-specific alpha-Cre mice with Vhl ^floxed mice and p107 ^-/-mice, we got VhlKO, p107KO, and p107/VhlDKO mice. Whole mount retinal IB4 staining, and fundus fluorescein angiography (FFA) were performed to evaluate the retinal vascular vessels. Immunofluorescence staining studied retinal cell types, cell proliferation, and cell death. RNA sequencing, chromatin immunoprecipitation (CHIP), and dual luciferase  reporter assay were also performed to study the retinal transcriptome, the binding of p107 protein to the promoter region of Hif target genes, and the effect of the p107 protein on the transcriptional activity of the Hif target genes. Results: p107/VhlDKO mice have delayed regression of hyaloid vessels, retinal degeneration, and retinal neovascularization. The p107 protein significantly inhibits the Hif pathway activity in VhlKO retinas. It can also bind to the promoter regions and suppress the transcriptional activity of several Hif target genes, including Vegfa, Kdr, and Tek. Conclusions:The p107 protein inhibits angiogenesis in the VhlKO retina, as it can bind and inhibit Hif target genes related to retinal angiogenesis.

眼附属器淋巴组织增生性疾病作为一类疾病的总称，包括了良性淋巴组织增生、非典型性淋巴组织增生、IgG4相关眼病以及多种恶性淋巴瘤在内的数十种疾病类型。临床诊断此类疾病应将患者眼部体征、影像学检查与病理学检查紧密结合。随着免疫表型及分子病理等检测技术的进步，此类疾病之间的鉴别诊断正逐渐清晰。本文就眼附属器淋巴组织增生性疾病进行系统性描述，并重点探讨该类疾病的病理鉴别诊断。

Ocular adnexal lymphoproliferative disease, as a general term, contains reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, IgG4 related ocular disease and malignant lymphoma. The clinical diagnosis of this kind of disease should integrate patient’s symptoms, imaging features and pathology characteristics. Development of immunophenotyping, molecular pathology and other detection technology will help with the differential diagnosis of ocular adnexal lymphoproliferative disease. This article is going to discuss the etiology, epidemiology,diagnosis and treatment of ocular adnexal lymphoproliferative disease, with a focus on the clinicopathological differential diagnosis of such disease.

眼附属器淋巴组织增生性疾病作为一类疾病的总称，包括了良性淋巴组织增生、非典型性淋巴组织增生、IgG4相关眼病以及多种恶性淋巴瘤在内的数十种疾病类型。临床诊断此类疾病应将患者眼部体征、影像学检查与病理学检查紧密结合。随着免疫表型及分子病理等检测技术的进步，此类疾病之间的鉴别诊断正逐渐清晰。本文就眼附属器淋巴组织增生性疾病进行系统性描述，并重点探讨该类疾病的病理鉴别诊断。

Ocular adnexal lymphoproliferative disease, as a general term, contains reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, IgG4 related ocular disease and malignant lymphoma. The clinical diagnosis of this kind of disease should integrate patient’s symptoms, imaging features and pathology characteristics. Development of immunophenotyping, molecular pathology and other detection technology will help with the differential diagnosis of ocular adnexal lymphoproliferative disease. This article is going to discuss the etiology, epidemiology, diagnosis and treatment of ocular adnexal lymphoproliferative disease, with a focus on the clinicopathological differential diagnosis of such disease.