Extracellular Vesicles Mediate Anti-Oxidative Response-In Vitro Study in the Ocular Drainage System

Area of Science:

• Cell Biology
• Ocular Science
• Biochemistry

Background:

• Extracellular vesicles (EVs) mediate cell signaling, but their protective role during oxidative stress (OS) is understudied.
• The eye's drainage system, including the non-pigmented ciliary epithelium (NPCE) and trabecular meshwork (TM), is uniquely exposed to OS and implicated in glaucoma.
• EVs in aqueous humor may play a role in glaucoma pathophysiology.

Purpose of the Study:

• To investigate if EVs from OS-exposed NPCE cells deliver protective signals to TM cells.
• To determine the impact of these EVs on key OS and glaucoma-related pathways (Nrf2-Keap1 and Wnt).

Main Methods:

• EVs were isolated from NPCE cells cultured under OS and control conditions.
• These EVs were incubated with TM cells.
• Effects on Nrf2-Keap1 pathway activation, Wnt pathway, antioxidant gene expression (qRT-PCR), and OS markers were evaluated.

Main Results:

• EVs from OS-exposed NPCE cells significantly protected TM cells against direct OS.
• TM cells showed increased uptake of these EVs and higher cytosolic Nrf2 levels.
• EVs attenuated Wnt protein expression and activated antioxidant genes in TM cells, alongside reduced OS markers and increased antioxidant enzyme activity.

Conclusions:

• EVs from OS-exposed NPCE cells convey protective signals, activating antioxidant pathways and mitigating OS in TM cells.
• Oxidized proteins within EVs likely contribute to this intercellular communication.
• These findings suggest a broader role for EVs in transmitting antioxidant defense signals across tissues, with implications for glaucoma research.