Changes in BDNF and neurotrophin receptor expression in degenerating and regenerating rat retinal ganglion cells

Abstract

Purpose: Exogenously applied BDNF has been shown to rescue rat retinal ganglion cells (RGCs) from axotomy-induced apoptotic death, presumably via activation of its high affinity receptor TrkB. Since both TrkB and BDNF are endogenously expressed in RGCs, auto- or para-crine neurotrophic loops in the retina may be involved. In the present study, we investigated whether expression levels of BDNF, TrkA, TrkB, TrkC and p75 protein in RGCs are specifically regulated following axonal lesion and during regeneration of optic fibres in the adult rat.

Methods: By double labelling retinal cryosections with Fluorogold and respective antibodies we determined the percentage of RGCs expressing the above-mentioned markers. In addition, mRNA levels of BDNF and TrkB were measured using quantitative RT-PCR.

Results: Compared to controls the number of BDNF-positive RGCs increased twofold 2 days after axotomy and the percentage of RGCs expressing TrkB was elevated by 50 %. Correspondingly, mRNA levels of BDNF increased about twofold 2 days after axotomy. During regen-eration, the percentage of BDNF-immunoreactive RGCs was further elevated compared to axotomy alone. The number of TrkA-positive RGCs doubled after axotomy, whereas no significant change in TrkC expression was observed. P75 expression was not detected in adult rat RGCs.

Conclusion: Our results suggest that intrinsic rescue mechanisms may contribute to short term neuronal survival and axonal regeneration of RGCs after axonal lesions.