Angiotensin II and aldosterone activate retinal microglia

Area of Science:

• Ophthalmology
• Neuroscience
• Endocrinology

Background:

• Microglial cells contribute to neuroinflammation and vascular damage in ischemic retinopathies.
• The renin-angiotensin aldosterone system (RAAS) plays a role in these processes.
• Angiotensin II (Ang II) and aldosterone are key RAAS effectors implicated in retinal pathology.

Purpose of the Study:

• To investigate the role of Ang II and aldosterone in retinal microglial activation.
• To determine if Ang II and aldosterone increase microglial density, reactive oxygen species (ROS), and pro-angiogenic/pro-inflammatory factors.
• To explore the effects of RAAS inhibitors on these processes.

Main Methods:

• Utilized two in vivo animal models: transgenic Ren-2 rats (overexpressing Ang II) and Sprague Dawley rats with aldosterone infusion and ischemic retinopathy.
• Conducted in vitro studies using primary retinal microglia cultures exposed to hypoxia.
• Administered RAAS inhibitors: valsartan (Angiotensin type 1 receptor), spironolactone (mineralocorticoid receptor), and FAD286 (aldosterone synthase).

Main Results:

• Both in vivo models showed increased microglial density in the retina.
• Hypoxia increased ROS and NADPH oxidase (NOX) isoform expression in cultured microglia.
• RAAS inhibitors reduced ROS, NOX expression, and levels of vascular endothelial growth factor (VEGF), CCL5, interferon γ, IL-6, TIMP-1, and various chemokines.

Conclusions:

• Angiotensin II and aldosterone promote retinal microglial activation.
• The RAAS is implicated in the pathogenesis of ischemic retinopathies.
• Targeting the RAAS may offer therapeutic strategies for ischemic retinopathies.