Morphometrical analysis of dendritic arborization in axotomized retinal ganglion cells

Abstract

It has been reported that section of the optic nerve in mammals causes death in >90% of the retinal ganglion cells (RGCs). The cells which survive the section experience an irreparable loss of many of their dendritic segments and a rapid retraction of the dendritic tree. However, some growth cones and abnormal processes have been also reported. Our aim was to make a quantitative study of the morphological changes found in rabbit RGCs after optic nerve section. The morphometrical analysis of the RGCs which survived the axotomy showed an increase in the diameter of the soma and a significant increase in the area of the dendritic field; also, the length of the dendritic segments was significantly longer in axotomized RGCs than in control cells. Terminal dendritic segments (T) and preterminal segments (PT) were both measured in control and axotomized cells; the length ratio of T : PT segments was significantly greater in the axotomized cells than in the controls. We conclude that RGCs which survived the axotomy experienced a significant growth of their terminal dendritic branches.

Long-Term Gene Therapy Causes Transgene-Specific Changes in the Morphology of Regenerating Retinal Ganglion Cells

“…Consistent with these complex effects, we found that RGCs were differentially affected depending on whether RGCs were transduced or non-transduced. Dendritic field area was consistently increased in RGC within rAAV2-BDNF-GFP injected eyes, and was accompanied by increased dendritic length, specifically due to longer nodal segments, suggesting interstitial growth [46]. Perhaps surprisingly, the increased growth was not accompanied by changes in branch density, perhaps due to altered dynamics of loss and formation of dendritic branches; in Xenopus tadpoles, target-derived (tectal) BDNF increases, whereas local (retinal) BDNF decreases, RGC dendrite complexity [58].…”

“…These changes did not obviously restore regenerating RGCs towards a more “normal” morphology, but rather added to the effects that were induced post-injury; thus BDNF further increased dendritic field size and CNTF reduced complexity in RGCs whose dendritic arbors had become larger [46] and less complex [37] following optic nerve lesion and PN transplantation. Furthermore, all three transgenes induced abnormal dendrite growth that was not restricted to normal sub-laminae within the IPL.…”

“…Abnormal morphologies were most frequent in rAAV2-CNTF-GFP and rAAV2-BDNF-GFP injected retinae, suggesting that these two transgenes promote aberrant arborization and growth beyond what is normally observed following ON crush or PN transplantation [46], [51], [78].…”

Targeting KVchannels rescues retinal ganglion cells in vivo directly and by reducing inflammation

“…MgTx significantly increased (bFGF) synaptic protein, synaptophysin, is consistent with an earlier observation that surviving RGCs have expanded dendritic trees. 15 Further indications of inflammation (Fig. 1J) were the increased expression of TNFα and the IL1-receptor antagonist (IL-1ra); and cFos, which can be upregulated by TNFα in the injured CNS.…”

Low‐hemorrhage‐risk surgical approach to expose the optic nerve in rabbits without bony removal and rectus resection

“…Different from the aims of establishing an animal model with optic nerve injury reported in a variety of studies, 7–16 in our proposed implementation the optic nerve was to be accessed via a simple surgical procedure in order to protect both the globe and optic nerve from secondary disturbance or impairment. Based on the specific requirements of our project and the anatomical features of the rabbits, a novel surgical approach of optic nerve exposure through the orbital process of the frontal bone has been explored.…”