Calbindin 2-specific deletion of arginase 2 preserves visual function after optic nerve crush

Area of Science:

• Neuroscience
• Ophthalmology
• Mitochondrial Biology

Background:

• Global deletion of mitochondrial arginase 2 (A2) previously showed neuroprotection following optic nerve crush (ONC).
• The cell-specific role of A2 in ONC-induced retinal neurodegeneration remains unclear.

Purpose of the Study:

• To investigate the cell-specific function of arginase 2 (A2) in retinal neurodegeneration after optic nerve crush (ONC).
• To determine the impact of A2 overexpression on mitochondrial function in retinal neurons.

Main Methods:

• Utilized cell-specific A2 knockout mouse models (neuronal, myeloid, endothelial) and wild-type controls.
• Assessed neuronal survival, retinal function, inflammatory markers, and apoptotic pathways post-ONC.
• Examined mitochondrial function and Drp1 expression in R28 cells with altered A2 levels.

Main Results:

• Neuronal-specific A2 deletion (Calb2 A2 KO) significantly improved neuronal survival and retinal function post-ONC.
• Deletion of A2 in myeloid or endothelial cells did not affect neuronal loss.
• Neuronal A2 deletion suppressed inflammatory mediators, apoptotic markers, and enhanced pro-survival signaling.
• A2 overexpression impaired mitochondrial respiration and increased Drp1 expression in R28 cells.

Conclusions:

• Neuronal expression of arginase 2 (A2) is detrimental to retinal neurons following injury.
• Targeting neuronal A2 offers a potential therapeutic strategy for limiting optic nerve injury-induced neurodegeneration.
• Arginase 2 influences mitochondrial dynamics and function, contributing to neurotoxicity after ONC.