Targeting endothelial ERG to mitigate vascular regression in retinopathies

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) involve retinal capillary loss and pathological neovascularization.
• Erythroblast transformation-specific (ETS) transcription factors ERG and FLI1 are crucial for endothelial cell homeostasis.

Purpose of the Study:

• To investigate the role of ERG and FLI1 in the pathogenesis of ROP and DR.
• To explore therapeutic strategies targeting ETS factors for retinopathy treatment.

Main Methods:

• Utilized a mouse model of ROP and human DR patient samples.
• Generated a mouse model with inducible endothelial cell-specific overexpression of Erg.
• Performed genetic deletion of endothelial Erg and Fli1.

Main Results:

• ERG and FLI1 were downregulated in retinal endothelial cells during early stages of ROP and DR.
• Erg overexpression in mice mitigated capillary regression, neuron death, and neovascularization in ROP and DR models.
• Simultaneous deletion of endothelial Erg and Fli1 promoted regression of pathological capillaries in ROP.

Conclusions:

• Homeostatic endothelial ETS factors ERG and FLI1 are critical for preventing capillary regression in retinopathy.
• Maintaining even one ETS factor prevents regression, offering potential therapeutic targets for retinopathies.