Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.
Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China; Guangdong Key Laboratory of Brain, Function and Diseases, Jinan University, Guangzhou, China; Joint International Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan University, Guangzhou, China.
Shanshan
S
Peng
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Zhe
Z
Shi
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Huanxing
H
Su
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China; Guangdong Key Laboratory of Brain, Function and Diseases, Jinan University, Guangzhou, China; Joint International Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan University, Guangzhou, China.
Kwok-Fai
KF
So
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China; Guangdong Key Laboratory of Brain, Function and Diseases, Jinan University, Guangzhou, China; Joint International Research Laboratory of CNS Regeneration, Ministry of Education of PRC, Jinan University, Guangzhou, China. Electronic address: qicui@yahoo.com.
Qi
Q
Cui
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D009900:Optic Nerve / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*
D015525:Fatty Acids, Omega-3; D017868:Cyclic AMP-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3
ERK1/2 pathway; Omega-3 fatty acids; Optic nerve injury; Retinal ganglion cell; Survival; cAMP