The exact physiological role of BDNF in the survival of RGCs is still not fully clear. Exogenous BDNF transiently increases the survival of RGCs after axotomy or optic nerve injury.
13 20 21 53 It has been demonstrated that BDNF retrogradely transported from the target plays a role in the maintenance of RGCs,
54 but other studies suggest that a substantial fraction of the BDNF found in retina is derived from local sources, suggesting that BDNF could act as an autocrine trophic factor supporting RGC survival.
55 56 Moreover, it has been demonstrated that BDNF-immunopositive RGCs and the percentage of RGCs expressing TrkB are increased after axotomy, suggesting that intrinsic rescue mechanisms may contribute to short-term survival.
57 Finally, BDNF-null mice
58 and TrkB-null mice
59 do not exhibit developmental losses in RGCs. In our study, administration of BDNF did not significantly modify the survival of cultured RGCs. Possible explanations are that endogenous BDNF levels produced by porcine RGCs in culture
60 are sufficient to support RGC survival or that the effect of BDNF on survival in vitro is lower than in vivo, due to the restricted number of factors.
41 It has also been proposed that BDNF may limit its own neuroprotective effect through downregulation of its receptor TrkB after excessive BDNF application.
61 62 Finally, Meyer-Franke et al.
63 have demonstrated that purified postnatal rat RGCs require elevation of intracellular cAMP levels to render them fully sensitive to treatment with neurotrophic factor, and similar mechanisms may operate in the model used in the current study.
Although BDNF did not influence survival, it stimulated changes in soma size and neurite elongation. BDNF increased the mean soma area of RGCs in culture, which correlates with a higher number of large RGCs in this condition
(Fig. 6B) . Such differential responses may reflect differences in the number and type of TrkB receptors, because it has been demonstrated that the number of TrkB-truncated receptors varies depending on the soma size of the RGCs.
64 In agreement with these data, BDNF has been shown to enlarge significantly the mean soma profile of human dopaminergic neurons,
65 and to exert different effects on survival of small and large RGCs in rat retina cultures,
25 with large RGCs exhibiting higher affinity to BDNF than medium RGCs.
10
In the visual system, neurotrophins influence neurite outgrowth in vitro
24 and in vivo.
26 66 It has been demonstrated that exogenous BDNF regulates RGC dendritic and axonal arborization in
Xenopus in vivo
67 and enhances axon growth in individual RGCs of rats,
68 possibly through the TrkB receptor.
69 In our study, BDNF increased both the length and number of neurites in adult porcine RGCs.