RPE cells modulate subretinal neovascularization, but do not cause regression in mice with sustained expression of...

Area of Science:

• Ophthalmology
• Angiogenesis Research
• Retinal Biology

Background:

• Previous studies suggest retinal pigment epithelium (RPE) causes regression of choroidal neovascularization (CNV) when angiogenic stimuli are withdrawn.
• The role of RPE in sustained CNV, particularly with continuous angiogenic stimulus, remains unclear.
• This study investigates the long-term behavior of RPE and CNV in a model with a sustained angiogenic stimulus.

Purpose of the Study:

• To investigate the long-term course of choroidal neovascularization (CNV).
• To examine the behavior of the retinal pigment epithelium (RPE) in the presence of a sustained angiogenic stimulus.
• To determine if RPE causes regression of neovascularization (NV) under sustained VEGF expression.

Main Methods:

• Utilized rhodopsin/VEGF transgenic mice (V-6 line) with sustained angiogenic stimulus.
• Measured mRNA levels of VEGF, VEGF-R1, and VEGF-R2 via RT-PCR at multiple time points (0.75 to 12 months).
• Analyzed retinal flatmounts using fluorescence microscopy and performed light and electron microscopy on eye tissues.

Main Results:

• Vascular Endothelial Growth Factor (VEGF) and its receptor mRNA levels remained constant throughout the study.
• Choroidal neovascularization (CNV) lesions initially grew and merged into networks by 6 months.
• Retinal Pigment Epithelium (RPE) cells surrounded chronic NV lesions, reestablishing the outer blood-retinal barrier without causing regression; some vessels became unperfused.

Conclusions:

• Despite sustained VEGF expression, neovascularization (NV) growth plateaued in older mice.
• Retinal Pigment Epithelium (RPE) cells modulate neovascularization (NV) by barrier reestablishment, not regression.
• Findings challenge prior conclusions that RPE actively causes regression of choroidal neovascularization (CNV).