Retinal Ganglion Cell In Model Research Articles

Astragalus membranaceus Injection Protects Retinal Ganglion Cells by Regulating the Nerve Growth Factor Signaling Pathway in Experimental Rat Traumatic Optic Neuropathy.

Activation of the nerve growth factor (NGF) signaling pathway is a potential method of treatment for retinal ganglion cell (RGC) loss due to traumatic optic neuropathy (TON). The present study aimed to explore the biological effects of injecting Astragalus membranaceus (A. mem) on RGCs in an experimental TON model. Adult male Wistar rats were randomly divided into three groups: sham-operated (SL), model (ML), and A. mem injection (AL). The left eyes of the rats were considered the experimental eyes, and the right eyes served as the controls. AL rats received daily intraperitoneal injections of A. mem (3 mL/kg), whereas ML and SL rats were administered the same volume of normal saline. The TON rat model was induced by optic nerve (ON) transverse quantitative traction. After two-week administration, the number of RGCs was determined using retrograde labeling with Fluoro-Gold. The protein levels of NGF, tyrosine kinase receptor A (TrkA), c-Jun N-terminal protein kinase (JNK), JNK phosphorylation (p-JNK), and nuclear factor kappa-B (NF-κB) were assessed using western blotting. The levels of p75 neurotrophin receptor (p75NTR) and NF-κB DNA binding were examined using real-time PCR and an electrophoretic mobility shift assay. In addition, the concentrations of JNK and p-JNK were assessed using an enzyme-linked immunosorbent assay. Results. The number of RGCs in ML was found to be significantly decreased (P < 0.01) relative to both AL and SL, together with the downregulation of NGF (P < 0.01), TrkA (P < 0.05), and NF-κB (P < 0.01); upregulation of p75NTR mRNA (P < 0.01); and increased protein levels of JNK (P < 0.05) and p-JNK (P < 0.05). Treatment using A. mem injection significantly preserved the density of RGCs in rats with experimental TON and markedly upregulated the proteins of NGF (P < 0.01), TrkA (P < 0.05), and NF-κB (P < 0.01) and downregulated the mRNA level of p75NTR(P < 0.01), as well as the proteins of JNK (P < 0.05) and p-JNK (P < 0.01). Thus, A. mem injection could reduce RGC death in TON induced by ON transverse quantitative traction by stimulating the NGF signaling pathway.

Protection of Mouse Retinal Ganglion Cell Axons and Soma from Glaucomatous and Ischemic Injury by Cytoplasmic Overexpression of Nmnat1

The Wlds mutation affords protection of retinal ganglion cell (RGC) axons in retinal ischemia and in inducible and hereditary preclinical models of glaucoma. We undertook the present study to determine whether the Nmnat1 portion of the chimeric protein provides axonal and somatic protection of RGCs in models of ischemia and glaucoma, particularly when localized to nonnuclear regions of the cell. The survival and integrity of RGC axons and soma from transgenic mice with confirmed cytoplasmic overexpression of Nmnat1 in retina and optic nerve (cytNmnat1-Tg mice) were examined in the retina and postlaminar optic nerve 4 days following acute retinal ischemia, and 3 weeks following the chronic elevation of intraocular pressure. Ischemia- and glaucoma-induced disruptions of proximal segments of RGC axons that comprise the nerve fiber layer in wild-type mice were both robustly abrogated in cytNmnat1-Tg mice. More distal portions of RGC axons within the optic nerve were also protected from glaucomatous disruption in the transgenic mice. In both disease models, Nmnat1 overexpression in extranuclear locations significantly enhanced the survival of RGC soma. Overexpression of Nmnat1 in the cytoplasm and axons of RGCs robustly protected against both ischemic and glaucomatous loss of RGC axonal integrity, as well as loss of RGC soma. These findings reflect the more pan-cellular protection of CNS neurons that is realized by cytoplasmic Nmnat1 expression, and thus provide a therapeutic strategy for protecting against retinal neurodegeneration, and perhaps other CNS neurodegenerative diseases as well.