# Retinal Astrocytes: Key Coordinators of Developmental Angiogenesis and Neurovascular Homeostasis in Health and Disease

## TL;DR

Retinal astrocytes help build and maintain healthy blood vessels in the eye, but can contribute to disease when they become reactive, offering new therapeutic targets for vision loss.

## Contribution

This review highlights the dual role of retinal astrocytes in both promoting and preventing retinal vascular disease, suggesting new therapeutic strategies.

## Key findings

- Retinal astrocytes guide normal blood vessel formation and maintain the blood-retinal barrier during development.
- In diseases like diabetic retinopathy, reactive astrocytes can promote inflammation and abnormal vessel growth.
- Tuning astrocyte polarization could help preserve retinal vascular integrity and treat blinding diseases.

## Abstract

Many blinding eye diseases, such as diabetic retinopathy and age-related macular degeneration, are caused by abnormal blood vessel growth and fluid leakage in the retina. While current treatments primarily focus on suppressing the blood vessels themselves, this review explores a crucial but often overlooked controller of eye health: retinal astrocytes. These star-shaped support cells act as “architects” during eye development, building a structural template to guide normal blood vessel formation and sealing vessels to prevent leaks. However, this study highlights that under disease conditions, these helpful cells can switch their behavior, mistakenly fueling inflammation and destructive vessel growth instead of preventing it. We summarize current knowledge on how these cells develop, interact with neurons, and change during illness. This work is valuable to society because it suggests a new direction for medical research. By understanding how to switch these cells back to a protective state, scientists can develop novel therapies to preserve vision that go beyond the limitations of current treatments.

Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood–retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity.