Optic Nerve Crush Does Not Induce Retinal Ganglion Cell Loss in the Contralateral Eye

Area of Science:

• Neuroscience
• Ophthalmology
• Immunology

Background:

• Optic nerve crush (ONC) models optic nerve trauma, causing significant retinal ganglion cell (RGC) loss and vision impairment.
• Contralateral, uninjured eyes are typically assumed to be unaffected by unilateral ONC.
• Recent studies suggest microglia activation in the contralateral eye post-ONC, raising questions about potential RGC loss.

Purpose of the Study:

• To investigate whether unilateral optic nerve crush (ONC) induces retinal ganglion cell (RGC) loss in the contralateral, uninjured eye.
• To quantify RGC numbers and density using advanced algorithms and deep learning tools.
• To determine if early microglial responses in the contralateral eye have immediate consequences on RGC survival.

Main Methods:

• Quantification of RGC total number and density across entire retinas using the RGCode algorithm and a novel deep-learning tool (RGC-Quant).
• Analysis of microglia response and number in the contralateral eye post-ONC.
• Comparison of RGC markers (Brn3a and RBPMS) and their co-labeling in different mouse models (Cx3cr1creERT2 and C57BL6/J) and sexes.

Main Results:

• A short-term microglia response was confirmed in the contralateral eye after ONC, without changes in overall microglia numbers.
• No significant RGC loss was detected in the contralateral retinas compared to naive retinas 5 weeks after ONC induction.
• The discrepancy in findings was not explained by mouse model, sex, or direct comparison of RGC markers Brn3a and RBPMS.

Conclusions:

• Unilateral optic nerve injury triggers a microglial response in the contralateral eye.
• This microglial response does not result in immediate RGC loss in the uninjured contralateral eye.
• The contralateral eye should be considered a separate entity and not used as a control in ONC studies.