Exactly how TrkB activation provides benefit to the photoreceptors and retina is still not well understood, though there is evidence that BDNF may play a role in this effect. The expression of retinal BDNF, a ligand of TrkB, is widespread in the retina and is upregulated during exercise.
10,11 In rodents, BDNF has been localized to retinal ganglion cells, amacrine cells, cone outer segments, and Muller cells.
37–40 In teleost fish used in aging research, BDNF mRNA was detectable in all retinal layers.
41 Receptors for BDNF and TrkB have been colocalized to the retinal pigmented epithelium, retinal ganglion cell layer, inner plexiform layer, INL, outer plexiform layer, and Muller cells in rats subjected to toxic light conditions.
42,43 Furthermore, Di Polo et al.
38 reported colocalization of BDNF and TrkB receptor proteins in red-green–sensitive cone outer segments in rat retinas. However, whether BDNF could have a direct effect on photoreceptors remains unclear as TrkB signaling is not solely governed by BDNF. Other ligands of TrkB include neurotrophin-3, neurotrophin-4 (NF4), and nerve growth factor (NGF), all of which influence survival and development of neurons.
44 Of these, NF4 and NGF have also been observed to be upregulated in the brain after exercise.
45,46 Additionally, downstream targets of BDNF upregulation and increased TrkB receptor activation may activate mechanistic targets such as rapamycin complex 1.
47 While these factors have not been observed to be upregulated in the retina after exercise, our data do not rule out their potential contributions to the protective effects of exercise through TrkB activation. Future experiments should pursue quantification of these factors in the retina post exercise to complement the observations made in this study.