Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy

Nitza Goldenberg-Cohen, Shimrit Dadon-Bar-El, Murat Hasanreisoglu, Bat Chen R. Avraham-Lubin, Olga Dratviman-Storobinsky, Yoram Cohen, Dov Weinberger

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To investigate the neuroprotective effect of brimonidine following induction of ischaemic optic neuropathy in rodents (rAION). Methods: Mice were treated with an intraperitoneal injection of brimonidine 48, 24 or 0 h before rAION induction or eye drops for 5 days after rAION induction. Retinal ganglion cell (RGC) loss and expression of genes involved in the angiogenesis (vascular endothelial growth factor [VEGF], pigment epithelium-derived factor [PEDF], The epidermal growth factor homology domains-2 [Tie-2]), ischaemia (haem oxygense-1 [HO-1], hypoxia-inducible factor 1α [HIF-1α], endothelial nitric oxide synthase [eNOS]) and oxidative stress (superoxide dismutase-1 [SOD-1], glutathione peroxidase-1 [GPX-1]) response to ischaemic damage were compared with sham or rAION-untreated mice. Results: No RGC loss was detected in the brimonidine-treated mice. Effect of post-rAION eye drops: day 1 - no decrease in retinal mRNA levels of angiogenesis-related genes, increase in ischaemia- and oxidative stress-related genes except HIF-1α; day 3 - baseline or higher levels of oxidative and ischaemia-related genes except HIF-1α, increase in VEGF, decrease in PEDF; day 21 - no change in angiogenesis-related genes. Effect of pre-rAION injection: baseline levels of angiogenesis-related genes with all injection schedules; increase in ischaemia-related genes with 48-h and 0-h pretreatment; decrease in HO-1 and eNOS with 24-h pretreatment; increase in oxidative-related genes except GPX-1. In optic nerve tissue, HO-1, HIF-1α and SOD-1 decreased on day 1 after topical administration and were still below baseline on day 3. Conclusions: The increase in HO-1 associated with rAION is mitigated with brimonidine treatment, especially when administered intraperitoneally. Topical brimonidine apparently reduces VEGF, Tie-2, HIF-1α and GPX-1 expression on day 21. These results agree with published data and may have therapeutic implications for patients diagnosed with AION in the acute phase.

Original languageEnglish
Pages (from-to)718-729
Number of pages12
JournalClinical and Experimental Ophthalmology
Volume37
Issue number7
DOIs
StatePublished - Sep 2009

Keywords

  • Anterior ischaemic optic neuropathy in rodents (rAION)
  • Brimonidine
  • Gene expression
  • Mouse model
  • Neuroprotection

Fingerprint

Dive into the research topics of 'Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy'. Together they form a unique fingerprint.

Cite this