The ability of BDNF to preserve the dendritic integrity of both α and β cells after optic nerve injury is not surprising, given its role in shaping the dendritic morphologies of central nervous system (CNS) neurons, including retinal ganglion cells, during development.
57 58 In addition, it is well-known that ganglion cells in the normal adult retina express BDNF and its primary receptor, TrkB,
59 60 and that both are upregulated as a result of injury to the optic nerve.
42 61 Finally, numerous studies have demonstrated that intravitreous delivery of BDNF or viral-mediated enhancement of ganglion cell TrkB receptor levels can delay ganglion cell death after optic nerve injury.
7 8 9 11 13 48 49 51 62 The mechanism by which BDNF acts to counter the degenerative events most likely involves not only its ability to enhance neuronal activity,
46 but also its ability to activate the phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) and mitogen-activated protein kinase (MAPK) survival pathways via its interaction with full-length TrkB receptors.
48 49 51 Although retinal ganglion cells also possess truncated TrkB receptor isoforms, their role is less clear, since they lack the intracellular signaling domain characteristic of the full-length receptors. Typically, these receptors are not considered to be involved in signal transduction, but rather act to modulate the function of the full-length receptors.
63 Nevertheless, more recent work has shown that truncated TrkB receptors are capable of mediating ligand-induced changes in cellular physiology, although the mechanism and purpose remain undefined.
64 While the present study indicates that activation of these intracellular pathways at the time of the nerve injury prevents the degenerative events from developing, what remains to be determined is the duration of this protective influence, as well as the ability to reverse previously established degenerative changes.