Bioelectric impact of pathological angiogenesis on vascular function

Area of Science:

• Cardiovascular Biology
• Ophthalmology
• Bioelectricity

Background:

• Pathological angiogenesis is a hallmark of numerous diseases, including inflammatory, immune, malignant, and ischemic disorders.
• Despite advancements in molecular therapies, pathological angiogenesis remains a significant health challenge, necessitating a deeper understanding of its underlying pathophysiology.
• While transmembrane voltage is recognized for its role in vascular function, its involvement in pathological angiogenesis has not been previously investigated.

Purpose of the Study:

• To investigate the bioelectric properties of pathological angiogenesis in the retina.
• To determine if aberrant electrical activity contributes to the pathophysiology of neovascularization.
• To explore the functional consequences of altered vascular voltage on retinal blood flow regulation.

Main Methods:

• Utilized the perforated-patch technique to measure vascular transmembrane voltage in human retinal neovascular specimens and rodent models of retinal neovascularization.
• Performed electrophysiological experiments to analyze voltage transmission within the intraretinal vascular network.
• Assessed the vasomotor response of retinal arterioles to hypoxia in the presence of neovascularization.

Main Results:

• Discovered that pathological neovessels generate exceptionally high electrical voltage.
• Demonstrated that this voltage is transmitted from aberrant preretinal neovascular complexes into the intraretinal vascular network.
• Observed that extensive neovascularization leads to suprahyperpolarization of intraretinal blood vessels, fundamentally altering their response to hypoxia from compensatory dilation to anomalous constriction.

Conclusions:

• Pathological angiogenesis is associated with significant bioelectric alterations, including suprahyperpolarization of intraretinal vessels.
• This bioelectric dysregulation leads to hypoxia-induced vasoconstriction, a reversal of the normal physiological response.
• The findings suggest that the bioelectric impact of neovascularization may be a previously unrecognized mechanism that perpetuates hypoxia, thereby sustaining pathological angiogenesis.