Methylene blue promotes survival and GAP-43 expression of retinal ganglion cells after optic nerve transection

• Published in: Life sciences (1973) Vol. 262; pp. 118462 - 8
• Main Authors: Fung, Jacqueline C.L., Cho, Eric Y.P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.12.2020; Elsevier BV
• Subjects: Animals; Axon regeneration; Axon sprouting; Axons; Cell Survival - drug effects; Central nervous system; Cricetinae; Disease Models, Animal; Female; GAP-43 protein; GAP-43 Protein - genetics; Injuries; Intravitreal Injections; Methylene blue; Methylene Blue - administration & dosage; Methylene Blue - pharmacology; Microglia; Nerve Regeneration - drug effects; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neuroprotection; Neuroprotective agents; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Optic nerve; Optic Nerve - drug effects; Optic Nerve - pathology; Optic Nerve Injuries - drug therapy; Optic Nerve Injuries - physiopathology; Optic nerve injury; Regeneration; Retina; Retinal ganglion cell; Retinal ganglion cells; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - drug effects; Survival; Time Factors; Neuroprotection; Optic nerve injury; Axon regeneration; Retinal ganglion cell; Methylene blue; Microglia
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118462

Neurodegeneration of the optic nerve and retinal ganglion cells (RGCs) leads to progressive vision loss. As part of the central nervous system, RGCs show limited ability to regenerate and there is extensive search for neuroprotective agents for optic nerve damage. Methylene blue (MB) exhibits beneficial effects against various neurodegenerative diseases of the central nervous system. However, the mechanisms associated with its putative protection on neuronal survival and regeneration remain obscure. This study used the optic nerve transection model to examine the effects of MB on RGC survival, the expression of regenerative marker GAP-43 in RGCs and microglial activation. Axons of RGCs were injured by cutting the optic nerve. MB was injected intravitreally either immediately post-injury or delayed to 3 days post-injury. Using immunohistochemical staining, surviving RGCs, GAP-43-positive RGCs and microglial cells were quantified in wholemount retinas 7 days post-injury. Both immediate and delayed (a more clinically realistic situation) intravitreal injection of MB promoted RGC survival. MB also increased the number of GAP-43-positive RGCs, suggesting an enhanced ability of RGCs to regenerate. This was exemplified by the regenerative sprouting of axon-like processes from injured RGCs after MB treatment. The increase in RGC survival and GAP-43 expression correlated with an increase in the number of microglial cells. These results reveal that MB has survival-promoting and growth-promoting effects on RGCs after optic nerve injury. Together with the established safety profile of MB in humans, MB is a promising treatment for neurodegeneration and injury of the optic nerve. •Methylene blue promotes RGCs survival after optic nerve injury.•GAP-43 expression in RGCs is enhanced by methylene blue.•Microglial activation correlates with RGC survival and GAP-43 expression.•RGCs are potent to delayed delivery of methylene blue treatment.