Neuroprotection of retinal ganglion cells in BDNF over–expression mice with induced elevated intraocular pressure

Abstract

Abstract: : Purpose: To investigate the neuroprotective actions of brain–derived neurotrophic factor (BDNF) on retinal ganglion cells in mice with induced elevated intraocular pressure (IOP). It has been demonstrated that BDNF deprivation may play a key role in a glaucomatous RGC death in rats, and thus we propose that BDNF over–expression in the retina could exert neuroprotective actions against glaucomatous RGC damage. Methods: Argon laser was used to photocoagulate the limbal vein and episcleral veins of the left eye of wild type and BDNF over–expressed mice. Non–invasive tonometry measured the IOP of both eyes once a week after laser treatment until the mice was sacrificed. The mouse retinal ganglion cells (RGCs) were identified by an antiserum against Thy1,2, CD 90.2 or by retrograde labeling with DiI. RGCs were viewed and counted by confocal microscope. Phorsphorylated Akt(pAkt) and Bcl–2 protein expression in retinas were investigated in normal, high–IOP and BDNF over–expressed mice by Western blot. Results: In situ hybridization and RT–PCR analysis showed that BDNF was over–expressed in the brain as well as in the retina in the transgenic mice used in this study. RGCs in the eyes with elevated IOP in both wild type and BDNF over–expressed mice underwent apoptotic cell death, but the death rate of RGCs in the eyes with elevated IOP in BDNF–over–expressed mice (5.9% and 9.5% RGC death in 4 and 8 weeks after photocoagulation) was much lower than that in wild type mice (22.3% and 28% of RGC death in 4 and 8 weeks after photocoagulation). Moreover, pAkt and Bcl–2 were expressed at higher levels in the BDNF over–expression mice than in wild type mice with or without high IOP. Conclusions: Over–expression BDNF in the retina may exert neuroprotective actions against RGC death induced by elevated IOP. This neuroprotective action may be mediated by the Akt and Bcl–2 signaling pathway.

Keywords: ganglion cells • intraocular pressure • neuroprotection