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Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy
Author(s) -
GoldenbergCohen Nitza,
DadonBarEl Shimrit,
Hasanreisoglu Murat,
AvrahamLubin Bat Chen R,
DratvimanStorobinsky Olga,
Cohen Yoram,
Weinberger Dov
Publication year - 2009
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/j.1442-9071.2009.02108.x
Subject(s) - brimonidine , pedf , endocrinology , medicine , vascular endothelial growth factor , enos , oxidative stress , angiogenesis , nitric oxide synthase , ophthalmology , nitric oxide , glaucoma , vegf receptors
A bstract 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.