Heterogeneous Distribution of Axonal Cytoskeleton Proteins in the Human Optic Nerve

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PURPOSE. Cytoskeleton proteins play a critical role in maintainingretinal ganglion cell structure, viability, and function. Thisstudy documents the distribution of cytoskeleton protein subunitsin the various regions of the normal human optic nerveand identifies important relationships among mitochondria,myelin, and neurofilament proteins.METHODS. Twenty-three optic nerves from human cadaverswere used. Confocal microscopy was used to examine thedistribution of neurofilament light, neurofilament medium,neurofilament heavy (phosphorylated and unphosphorylated),neurofilament heavy (phosphorylated only), actin, and microtubuleassociated protein (MAP)-1 along the sagittal plane ofthe optic nerve. Comparisons were made among superior,middle, and inferior regions and also among temporal, central,and nasal portions of the optic nerve. Colocalization of neurofilamentlight, mitochondrial cytochrome c oxidase (COX), andmyelin was also performed.RESULTS. There are significant differences in the pattern anddistribution of neurofilament protein subunits, actin, andMAP-1 along the sagittal plane of the optic nerve. Cytoskeletonproteins and COX mitochondria are found in highest concentrationsin the prelaminar and lamina cribrosa regions. COXand neurofilament light occurs predominantly in unmyelinatednerve, with a significant decrease in concentration occurringon optic nerve myelination.CONCLUSIONS. The heterogeneous distribution of cytoskeletonproteins along the sagittal plane may be an important functionaladaptation that reflects the nonuniform nature of thephysiological and structural environment of the optic nerve.The heterogeneous distribution of cytoskeleton proteins mayalso partly account for the asymmetric pattern of optic nervedamage after intraocular pressure elevation.
Original languageEnglish
Pages (from-to)2824-2838
JournalInvestigative ophthalmology & visual science
Issue number6
Publication statusPublished - 2009


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