Chronic social defeat stress causes retinal vascular dysfunction.

Area of Science:

• Ophthalmology
• Neuroscience
• Vascular Biology

Background:

• Glaucoma pathophysiology involves vascular dysfunction and chronic stress.
• Understanding the link between stress, vascular health, and retinal ganglion cell (RGC) survival is crucial.

Purpose of the Study:

• To investigate if chronic stress induces retinal vascular dysfunction and subsequent RGC loss.
• To determine the long-term effects of chronic social defeat (CSD) stress on the murine retina.

Main Methods:

• Mice were subjected to CSD stress or control treatment.
• Evaluated intraocular pressure (IOP), corticosterone levels, adrenal gland weight, RGC survival (Brn-3a staining), and axon survival (PPD staining).
• Assessed retinal vascular autoregulation, vasoactive agent response, vascular mechanics, and endothelin-1 (ET-1) and alpha-smooth muscle actin (α-SMA) levels.

Main Results:

• CSD stress did not significantly alter IOP, RGC survival, or axon survival.
• CSD induced temporary hypercortisolemia and adrenal hyperplasia, which normalized over time.
• Irreversible impairment of retinal arteriolar autoregulation and endothelial function was observed post-CSD, with long-term changes in vascular mechanics.

Conclusions:

• Chronic stress does not cause IOP elevation or RGC loss in this model.
• CSD stress leads to persistent, irreversible retinal vascular dysfunction and altered vascular mechanics.
• Increased ET-1 levels and potential pericyte loss may contribute to stress-induced vascular damage.