phenanthrenes and Glaucoma

To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs) in a rat model of chronic glaucoma.. Eighty Wistar rats were randomly divided into triptolide group (n=40) and normal saline (NS) group (n=40). Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP), anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF)-α mRNA detection by reverse transcription-polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed.. Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05), with no statistical difference between the two groups (P>0.05). RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05). Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90) than the NS group (35.06±7.59) (P<0.05). TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01). The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia.. Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion.

Topics: Animals; Cell Survival; Disease Models, Animal; Diterpenes; Epoxy Compounds; Glaucoma; Injections, Intraperitoneal; Intraocular Pressure; Microglia; Phenanthrenes; Rats; Rats, Wistar; Retinal Ganglion Cells; Tumor Necrosis Factor-alpha

To investigate the changes in retinal microglia and retinal ganglion cell (RGC) survival after long-term administration of a Chinese herb extract, triptolide, in a DBA/2J mice. DBA/2J mice (n = 96) were administered triptolide (n = 48) 25 µg/kg or vehicle (n = 48) and were judged at 7, 9, 11 months of age. Long-term triptolide treatment tended to attenuate the anterior segment pathology in experimental group, though intraocular pressure was not significantly different between the two groups. In the experimental group, RGC survival was improved (7, 9, 11 months: p = 0.035, 0.004, 0.014), and microglia activation was suppressed based on a more ramified appearance (9, 11 months: p = 0.024, 0.013) and a lower total microglial cell count (7, 9, 11 months: p = 0.028, 0.025, 0.014). Double-immunofluorescence staining revealed TNF? localized to microglia, TNFR1 localized to the RGCs and nerve fiber layer. These findings indicate that long-term triptolide administration suppressed microglia activation and improved RGC survival in DBA/2J mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Disease Models, Animal; Diterpenes; Drugs, Chinese Herbal; Epoxy Compounds; Female; Follow-Up Studies; Glaucoma; Immunohistochemistry; Immunosuppressive Agents; Intraocular Pressure; Mice; Mice, Inbred DBA; Microglia; Phenanthrenes; Receptors, Tumor Necrosis Factor, Type I; Retinal Ganglion Cells; Treatment Outcome