Abstract
Retinal detachment (RD) leads to photoreceptor cell death secondary to the physical separation of the retina from the underlying retinal pigment epithelium. Intensifying photoreceptor survival in the detached retina could be remarkably favorable for many retinopathies in which RD can be seen. BNN27, a blood-brain barrier (BBB)-permeable, C17-spiroepoxy derivative of dehydroepiandrosterone (DHEA) has shown promising neuroprotective activity through interaction with nerve growth factor receptors, TrkA and p75NTR. Here, we administered BNN27 systemically in a murine model of RD. TUNEL+ photoreceptors were significantly decreased 24 hours post injury after a single administration of 200 mg/kg BNN27. Furthermore, BNN27 increased inflammatory cell infiltration, as well as, two markers of gliosis 24 hours post RD. However, single or multiple doses of BNN27 were not able to protect the overall survival of photoreceptors 7 days post injury. Additionally, BNN27 did not induce the activation/phosphorylation of TrkAY490 in the detached retina although the mRNA levels of the receptor were increased in the photoreceptors post injury. Together, these findings, do not demonstrate neuroprotective activity of BNN27 in experimentally-induced RD. Further studies are needed in order to elucidate the paradox/contradiction of these results and the mechanism of action of BNN27 in this model of photoreceptor cell damage.
Highlights
During retinal detachment (RD), photoreceptors are physically separated from the retinal pigment epithelium (RPE), the underlying supporting nourishing tissue of the retina
To determine the potential neuroprotective effect of BNN27 on the photoreceptors after experimental retinal detachment (RD), we examined the RD-induced cell death in the outer nuclear layer (ONL) by TUNEL assay
We have previously shown that nerve growth factor (NGF) mRNA levels are elevated following experimental RD4
Summary
During retinal detachment (RD), photoreceptors are physically separated from the retinal pigment epithelium (RPE), the underlying supporting nourishing tissue of the retina. This separation activates a signaling cascade that culminates in photoreceptor cell death mediated by significant cross talk between apoptosis, regulated necrosis and other cell death pathways[1,2,3,4,5]. DHEA is an intermediate in the biosynthesis of androgens and estrogens and treatment with this steroid can be problematic due to potential endocrine side effects[22,23,24,25] For this reason, effort has been made to develop analogues that will retain the anti-apoptotic properties while inhibiting their ability to convert to estrogens or androgens. In the present study, we investigated whether systemically administered BNN27 can protect photoreceptors from cell death in the murine model of experimental retinal detachment and how BNN27 administration can affect the detached retina
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