| There is no myelination in most mammalian retina but if the oligodendrocytes (OLs) abnormally appear in retina, it can lead to myelinated retinal nerve fibers which appear as white or gray white striated patches. The myelin in the retina may lead to visual dysfunction. For example, myelinated nerve fiber in the human retina may accompany with myopia and amblyopia. Its occurrence mechanism is not clear. Despite born to have myelin in lower vertebrates, the precise temporal dynamics of myelination in which oligodendrocytes involved, the origin of oligodendrocytes, their behavior in myelination and their function in zebrafish retina have not yet been clearly elaborated. Therefore, we focus on these aspects to study the oligodendrocyte and myelin sheath in the zebrafish retina which could provide a detailed insight into the formation of retinal myelination.Due to the lack of suitable oligodendrocyte transgenic lines, the studies of myelin in retina were confined to description of the developmental state of OLs and myelination by immunohistochemistry and EM evidence. As myelin and OLs exist in zebrafish retina and there are many OLs transgenic zebrafish line, zebrafish becomes a good vertebrate model to study the myelination in the retina. By means of Tg(olig2:egfp) transgenic line, we can intuitive and quantitative observe the temporal dynamics of myelination. We found that myelination starts at 28 day post fertilization (dpf). Accompanying the developmentof zebrafish, the number of OLs and retinal ganglion cells (RGCs) is continuous increasing; The density of Olig-2+cells and the expression of myelin basic protein (MBP) are increased with age and remain stable at 3 months post-fertilization (mpf); The ratio of Olig-2+vs. RGCs is decreased until 3 mpf. In order to know the source of OLs in retina, by injection fluorescent dye Dil into the third ventricle, Ono et al found DiI positive cell in chicken retina, which might indicate some OLs can migrate into chick myelinated retina from external of the eye. However, previous studies can not identify whether all OLs in retina are from external of the eye. Taking advantage of the whole eye forward flip and transplantation techniques, we directly proved that the oligodenrocytes in zebrafish retina are migration from the optic nerve rather than from the domestic source within the retina.By optic nerve transplantation, we can observe the morphology of single OL. We found that OLs at different ages exhibit different behaviors:younger OLs tend to generate longer but a fewer number of internodes, while adult matured OLs tend to generate shorter but a greater number of internodes. The age-related behavior changes in OLs are relianted on the cell intrinsic properties but not relianted on external environment. Though the OLs at different ages have different behaviors, their ability to wrap the axon is unchanged.While the diameter of myelinated axons is growing with age, the unmyelinated axons diameter is not significantly changed. Different from the other part of nervous system, oligodendrocytes wrap axon in a loose and one lamellae way in zebrafish retina. Regardless of ages, the ratio of the inner axonal diameter to the total outer diameter located within the range of ratio 0.6-0.7. These are very important for the maintenance of translucent zebrafish retina and nerve impulse conduction. Finally, taking use of optokinetic reflex behavior test and lysophosphatidylcholine induced retina demyelin model, we found that the the myelin in zebrafish eyes is functionally relevant to the elegant optokinetic reflex.Our study indicates that the myelination starts at 28 dpf; All the OLs in zebrafish retina are from external of to the eye; OLs at different ages have different behaviors that are decided by cell intrinsic properties; The myelin is functional in zebrafish retina. This study may provide more details for understanding the intraretinal myelin and its physiological characteristics. |
PDF Full Text Request