Retinal p75 and bax overexpression is associated with retinal ganglion cells apoptosis in a rat model of glaucoma

PURPOSE: The administration of neurotrophins has been clearly demonstrated to support survival of retina cells during a variety of insults. Increased levels of neurotrophins, such as the nerve growth factor (NGF), have been found in experimental models of glaucoma. Nevertheless, loss of retinal cells does occur in the course of ocular hypertension. Therefore, this study sought to address whether timely changes in NGF and its receptors, trkA(NGFR) and p75(NTR), might explain the progression of retinal damage during experimental glaucoma. METHODS: A well-characterized technique to induce glaucoma in rats was utilized. The animals were sacrificed after 10, 20 and 35 days from induction of glaucoma. Retinal ganglion cell (RGC) apoptosis, retinal expression of NGF protein as well as Bcl-2, Bax, trkA(NGFR) and p75(NTR) transcript expression were detected. The balance between trkA(NGFR) and p75(NTR) was examined, considering their anti- and pro-apoptotic role in cell death, respectively. RESULTS: We demonstrated that in our model of experimental glaucoma, the loss of retinal ganglion cells (RGCs) is accompanied by a timely increase of retinal NGF. Moreover, we found that the trkA(NGFR)/p75(NTR) mRNA ratio and the Bcl-2/Bax mRNA were both decreased, indicating a p75(NGFR) and Bax over-expression. CONCLUSIONS: Retinal NGF is over-expressed in experimental glaucoma, but this NGF increase is not sufficient to support survival of RGCs. The failure of NGF trophic support might be associated with the progressive up-regulation of p75(NTR) in relation to trkA(NGFR).