# From brain to eye: Annexin A1 and A2 as a key mediator of retinal neuroinflammation in Parkinson’s and Alzheimer’s disease

## TL;DR

Annexin A1 and A2 may help reduce retinal inflammation in Parkinson’s and Alzheimer’s diseases, offering potential new treatments.

## Contribution

Highlights annexin A1 and A2 as key regulators of retinal neuroinflammation in Parkinson’s and Alzheimer’s.

## Key findings

- Reduced AnxA1 activity may worsen inflammation in Parkinson’s retinal degeneration.
- AnxA1 signaling is crucial for clearing β-amyloid in Alzheimer’s retinal damage.
- AnxA1/AnxA2 pathways could serve as therapeutic targets for retinal degeneration in these diseases.

## Abstract

The retina, as an extension of the central nervous system, is highly susceptible to inflammatory and degenerative changes similar to those brain seen in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Annexin A proteins, particularly annexin A1 (AnxA1) and annexin A2 (AnxA2), may play key roles in regulating neuroinflammation and maintaining retinal homeostasis. AnxA1 provides strong anti-inflammatory and pro-resolution actions, limiting cytokine release and promoting a reparative microglial phenotype. AnxA2, which often acts as an S100A10-AnxA2 complex, supports inflammatory resolution through tPA- and TLR4-dependent pathways and contributes to glial stability. In PD, retinal degeneration mirrors brain pathology, and reduced AnxA1 activity may impair the resolution of inflammation. In AD, decreased AnxA1 signalling compromises β-amyloid clearance and maintains chronic neuroinflammation. However, endogenous release of AnxA1 or therapy with AnxA1-derived peptides is capable of promoting efficient phagocytosis by microglia, clearing the neurotoxic environment in AD brains. Overall, it is possible that coordinated AnxA1/AnxA2 activity may mitigate retinal damage, improve the removal of toxic aggregates, and preserve vision, highlighting annexin pathways as promising therapeutic targets for retinal degeneration in PD and AD. This makes it an interesting target for study during retinal degeneration in PD and AD.