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Updated: Jun 25, 2026

Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
MYDGF promotes pathological and physiological retinal angiogenesis via the Gαi1/3-Gab1-Akt-mTOR signaling
Ke-Ran Li1, Ping-Ping Fu2, Wen Bai1
1Jiangsu Key Laboratory of Molecular Targets and Intervention for Metabolic Diseases, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
Abstract:
Retinal neovascularization (RNV) is a potential vision-threatening process characterized by the abnormal growth of retinal vessels. Despite its clinical prevalence, the precise mechanisms governing RNV initiation and progression remain incompletely defined. Here we identify myeloid-derived growth factor (MYDGF) as a critical regulator of retinal vascular dynamics. Using single-cell RNA sequencing and human patient validation, we show that MYDGF is upregulated in retinal endothelial cells during proliferative diabetic retinopathy and mouse models of pathological neovascularization. In vitro, MYDGF promotes retinal endothelial cell proliferation, migration, and sprouting. In vivo, endothelial-specific MYDGF depletion inhibits both normal vascular development and pathological neovascularization in neonatal mice, and disrupting adult vascular homeostasis in male mice. MYDGF drives angiogenesis by activating the Akt-mTOR cascade through the Gαi1/3-Gab1 signaling complex; genetic depleting or mutation these components suppress MYDGF-induced Akt-mTOR activation and angiogenic responses. Together, MYDGF promotes retinal angiogenesis and maintains vascular homeostasis via the Gαi1/3-Gab1-Akt-mTOR signaling axis.
Insights
Myeloid-derived growth factor (MYDGF) drives retinal angiogenesis and vascular homeostasis. This factor is upregulated in conditions like diabetic retinopathy, promoting abnormal blood vessel growth.
Area of Science:
- Ophthalmology
- Vascular Biology
- Molecular Medicine
Background:
- Retinal neovascularization (RNV) is a major cause of vision loss.
- The molecular mechanisms driving RNV are not fully understood.
Purpose of the Study:
- To identify key regulators of retinal vascular dynamics.
- To elucidate the role of myeloid-derived growth factor (MYDGF) in RNV.
Main Methods:
- Single-cell RNA sequencing
- Human patient sample analysis
- In vitro cell culture assays
- In vivo mouse models of neovascularization and vascular homeostasis
Main Results:
- MYDGF is upregulated in retinal endothelial cells during pathological neovascularization.
- MYDGF promotes endothelial cell proliferation, migration, and sprouting in vitro.
- Endothelial-specific MYDGF depletion impairs normal and pathological retinal angiogenesis in vivo.
- MYDGF activates the Akt-mTOR pathway via the Gαi1/3-Gab1 signaling complex.
Conclusions:
- MYDGF is a critical regulator of retinal angiogenesis.
- MYDGF plays a dual role in promoting pathological neovascularization and maintaining vascular homeostasis.
- The Gαi1/3-Gab1-Akt-mTOR axis mediates MYDGF's angiogenic effects.
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