The effects and underlying mechanisms of S-allyl l-cysteine treatment of the retina after ischemia/reperfusion.

Abstract

PURPOSE:

Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury.

METHODS:

In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 μM H(2)O(2) for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches.

RESULTS:

The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The increased protein levels of HIF-1α, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 μM) and/or significantly (50 and/or 100 μM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively.

CONCLUSION:

SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1α, VEGF, and MMP-9.

• Authors: Yan-Qing Chen, Wynn H T Pan, Jorn-Hon Liu, Mi-Mi Chen, Chi-Ming Liu, Ming-Yang Yeh, Shen-Kou Tsai, Mason Shing Young, Xiu-Mei Zhang, Hsiao-Ming Chao
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 28 Issue 2 Pg. 110-7 (Apr 2012) ISSN: 1557-7732 [Electronic] United States
• PMID: 22054242 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• S-allylcysteine
• Matrix Metalloproteinase 9
• Mmp9 protein, rat
• Cysteine

Topics

• Animals
• Antioxidants (administration & dosage, therapeutic use)
• Cell Line
• Cysteine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis)
• Intraocular Pressure (drug effects)
• Ischemia (enzymology, metabolism, prevention & control)
• Matrix Metalloproteinase 9 (biosynthesis)
• Oxidative Stress (drug effects)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Reperfusion Injury (enzymology, metabolism, prevention & control)
• Retina (drug effects, enzymology, metabolism)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (biosynthesis)