Single-Cell Transcriptome Analysis Reveals That Hmga2 Regulates Neuroinflammation and Retinal Function by Modulating...

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Central retinal artery occlusion (CRAO) causes painless vision impairment due to retinal ischemia (RI).
• Müller cells are crucial for retinal homeostasis, regulating inflammation and oxidative stress post-RI.
• The specific role of Müller cells in middle cerebral artery occlusion (MCAO)-induced RI is not fully understood.

Purpose of the Study:

• To investigate the role of Müller cells in MCAO-induced retinal ischemia.
• To identify novel molecular targets and therapeutic strategies for treating RI.

Main Methods:

• Single-nucleus RNA sequencing to analyze retinal cell transcriptional changes after MCAO.
• Gene knockout of high-mobility group A2 (Hmga2) in Müller cells.
• Development and in vivo testing of hybrid nanoparticles (siRNA-Hmga2@LMM) for targeted siRNA delivery.

Main Results:

• A novel Müller cell subpopulation with high Hmga2 expression was identified post-RI.
• Hmga2 knockout reduced neuroinflammation and RI symptoms, potentially via PI3K pathway and autophagy regulation.
• Intravitreal injection of siRNA-Hmga2@LMM nanoparticles improved retinal function in RI models.

Conclusions:

• Hmga2 plays a significant role in Müller cells during retinal ischemia.
• Targeting Hmga2 with nanoparticle-delivered siRNA offers a promising therapeutic approach for RI.
• This study provides new mechanistic insights into Müller cell function and RI treatment.