Heat shock protein 40 enhances axon regeneration in a mouse model of traumatic optic neuropathy

Area of Science:

• Neuroscience
• Genetics
• Ophthalmology

Background:

• Optic nerve injury from trauma or glaucoma causes vision loss due to retinal ganglion cell death.
• While optic nerve regeneration is possible, current methods yield limited results.

Purpose of the Study:

• To identify genomic factors that enhance axon regeneration in the optic nerve.
• To understand the genetic basis of varying regenerative capacities in different mouse strains.

Main Methods:

• A forward genetics approach was used with BXD recombinant mouse strains.
• Optic nerve regeneration was induced by Pten knockdown in retinal ganglion cells, followed by optic nerve crush.
• Regenerating axons were quantified for number and distance traveled.

Main Results:

• Significant variation (7.5-fold in number, 4-fold in distance) in axon regeneration was observed across BXD strains.
• A quantitative trait locus on Chromosome 14 was identified, containing the gene Dnajc3.
• Dnajc3 (encoding HSP40) was confirmed to modulate axon regeneration; its knockdown decreased regeneration, while overexpression increased it.

Conclusions:

• Dnajc3 plays a critical role in enhancing both the extent and distance of optic nerve axon regeneration.
• Targeting Dnajc3 offers a potential therapeutic strategy for improving functional recovery after optic nerve damage in humans.