Pharmacological preconditioning by low dose cobalt protoporphyrin induces heme oxygenase-1 overexpression and alleviates retinal ischemia-reperfusion injury in rats.

Abstract

PURPOSE:

Retinal ischemia-induced neuronal death plays a crucial role in certain severe visual impairment diseases. The aims of this study were to investigate the effects of low dose cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), on the retina of rats against ischemia-reperfusion (IR) injury.

METHODS:

Retinal IR was achieved in rats by raising intraocular pressure for 60 min. CoPP (1 mg/ kg) was injected intraperitoneally 24 hr before IR. Retinal injury was assessed by the number of retinal ganglion cells (RGCs) seven days after reperfusion. TUNEL assay was used to detect the appearance of apoptotic cells 24 hr after reperfusion. The expressions of the HO-1 and Bax proteins were evaluated by Western blot.

RESULTS:

Both HO-1 expression, examined by Western blot, and enzyme activity were increased strongly after CoPP administration. Rats treated with CoPP before IR had more RGCs (p = 0.034) and less apoptotic cells (p = 0.04) together with downregulated Bax protein levels (p = 0.03) compared to ischemic rats without CoPP. The protective effects of CoPP were HO-1 dependent because the upregulation of HO-1 and the RGC protection were both abolished by the HO-1 inhibitor tin protoporphyrin (SnPP).

CONCLUSIONS:

In this study, we demonstrated that induction of HO-1 expression by low dose CoPP ameliorated retinal damage from IR injury. The favorable effect appears to be related with modulations of the apoptotic pathway.

• Authors: Pai-Huei Peng, Hsiao-Ming Chao, Shu-Hui Juan, Chau-Fong Chen, Jorn-Hon Liu, Mei-Lan Ko
• Journal: Current eye research (Curr Eye Res) Vol. 36 Issue 3 Pg. 238-46 (Mar 2011) ISSN: 1460-2202 [Electronic] England
• PMID: 21275512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bax protein, rat
• Protoporphyrins
• bcl-2-Associated X Protein
• Triiodothyronine
• cobaltiprotoporphyrin
• L-Lactate Dehydrogenase
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Alanine Transaminase
• Thyroxine

Topics

• Alanine Transaminase (blood)
• Animals
• Apoptosis
• Blotting, Western
• Female
• Heme Oxygenase (Decyclizing) (metabolism)
• In Situ Nick-End Labeling
• Injections, Intraperitoneal
• Ischemic Preconditioning
• L-Lactate Dehydrogenase (blood)
• Protoporphyrins (administration & dosage)
• Rats
• Rats, Wistar
• Reperfusion Injury (enzymology, physiopathology, prevention & control)
• Retinal Diseases (enzymology, physiopathology, prevention & control)
• Retinal Ganglion Cells (pathology)
• Retinal Vessels (physiology)
• Thyroxine (blood)
• Triiodothyronine (blood)
• bcl-2-Associated X Protein (metabolism)