Neuroprotective and axon growth promoting effects of intraocular inflammation do not depend on oncomodulin or the presence of large numbers of activated macrophages.
Retinal ganglion cells (RGCs) cannot regenerate their axons after injury and undergo apoptosis soon after an intraorbital injury of the optic nerve. However, RGCs reactivate their axonal growth program when inflammatory reactions occur in the eye, which enables them to survive axotomy and to regenerate lengthy axons into the lesioned optic nerve. Lens injury (LI) and zymosan injections can induce these beneficial processes and provoke also a strong accumulation of activated macrophages in the vitreous body. It has recently been suggested that macrophage-derived oncomodulin is the principal mediator of this phenomenon. We show here that oncomodulin is not significantly expressed in primary macrophages and that the intraocular levels of this protein do not increase after LI or zymosan treatment. Furthermore, greatly reducing the invasion of macrophages into the inner eye does not diminish the neuroprotective effects of LI, but rather increases axon regeneration into the optic nerve. Axon regeneration is correlated with the activation of retinal astrocytes and Müller cells. Our data suggest that intraocular inflammation mediates its main beneficial effects through factors other than oncomodulin and that the underlying mechanism might be independent of the presence of activated macrophages.
Hauk
Thomas G
TG
Department of Experimental Neurology, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
Müller
Adrienne
A
Lee
Jieun
J
Schwendener
Reto
R
Fischer
Dietmar
D
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002232:Carbocyanines / Q000378:metabolism; D002461:Cell Line, Transformed; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D007908:Lens, Crystalline / Q000293:injuries; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000150:complications; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D015054:Zymosan / Q000008:administration & dosage
D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D002232:Carbocyanines; D009419:Nerve Tissue Proteins; C034733:oncomodulin; C072024:carbocyanine dye DiIC12(3); D015054:Zymosan