title: Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats.
abstract: The purpose of the present study was to investigate the effects of administrations of triamcinolone acetonide and systemic methylprednisolone sodium succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of optic nerve crush. The treated groups either received triamcinolone immediately in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control group received intra-peritoneal injection with phosphate-buffered saline (PBS) after crush experiments. RGC density was counted by retrograde labeling with Fluorogold, and visual function was assessed by flash visual-evoked potentials. Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p-ERK) and signal transducer and activator of transcription 3 (p-STAT3) and immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve were conducted. Two and four weeks after optic nerve crush experiments, neither triamcinolone nor methylprednisolone treatment rescued the RGC from death in the central and mid-peripheral retinas compared with those of the corresponding optic nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed a prolonged latency of the P(1) wave in all treated groups (triamcinolone-treated: 123 ± 23 ms, methylprednisolone-treated: 133 ± 25 ms and PBS-treated: 151 ± 55 ms) after two weeks. TUNEL assays showed that there was no decrease in apoptotic cells in the RGC layers of both triamcinolone treated and methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p-ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or methylprednisolone treated rats. In addition, the number of ED1-positive cells was not attenuated at the lesion sites of the ON in either treatment group. Based upon these results, we conclude that neither retrobulbar administration of triamcinolone nor systemic administration of methylprednisolone has any neuroprotective effects in a rat model of optic nerve crush.
authors.affiliation: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Tzu Lun
authors.initials: TL
authors.lastname: Huang
authors.forename: Chung Hsing
authors.initials: CH
authors.lastname: Chang
authors.forename: Kung Hung
authors.initials: KH
authors.lastname: Lin
authors.forename: Min Muh
authors.initials: MM
authors.lastname: Sheu
authors.forename: Rong Kung
authors.initials: RK
authors.lastname: Tsai
mesh_terms: D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D053331:Ectodysplasins / Q000378:metabolism; D005074:Evoked Potentials, Visual; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000494:pharmacology
chemical_list: D053331:Ectodysplasins; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D008776:Methylprednisolone Hemisuccinate; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D014222:Triamcinolone Acetonide