Abstract
Purpose To determine the effect of osthole on the retina in a chronic cerebral hypoperfusion (CCH) rat model and to investigate its therapeutic activity. Methods Seventy-two rats were randomly allocated into 6 groups. CCH was induced by permanent bilateral common carotid artery occlusion (BCCAO) in five groups. Sham surgery was performed without occlusion of the artery in the sixth group (control group). Animals were administered with saline (model group), osthole (osthole-IG group), aspirin (aspirin group), or ginaton (ginaton group); the osthole-PI group was performed with peribulbar injection of osthole. Four rats in each group were sacrificed every 5 days after drug administration, and histopathology along with morphology of retina were observed. Fundus fluorescein angiography was performed before the animals were sacrificed at day 15. Retinal Akt, NF-κB, Bax, and Bcl-2 levels were assessed using immunohistochemistry, immunofluorescence, and reverse-transcription PCR; retinal injury was assessed using TUNEL in situ; retinal levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Results Fundus fluorescein angiography revealed the retinal vascular diameter in the osthole-IG group rats to be wider than that in the model, osthole-PI, aspirin, or ginaton group rats. Histological analysis of retinal tissue revealed an increase in retinal thickness in all treatment groups, and significant improvement was noticed in the osthole-IG group. TUNEL staining revealed fewer apoptotic cells in the osthole-IG and osthole-PI groups than in the other groups. For immunohistochemistry results, in the osthole-IG group, levels of NF-κB and Akt were lower than those in the other treated groups, while levels of the ratio Bcl-2/Bax were higher. Levels of MDA were lower and levels of SOD were higher in the osthole-IG group than in the other groups. Conclusions Osthole protects the retina from ischemia injury secondary to CCH induced by BCCAO, mainly through anti-inflammatory, antioxidant, and antiapoptotic effects.
Highlights
Chronic cerebral hypoperfusion (CCH) can lead to cognitive impairment and neuronal cell damage, via oxidative stress and inflammation [1]
We previously reported that the Rho/ MAPK/iNOS pathway was involved in chronic retinal ischemia (RI), leading to tissue inflammation and apoptosis in a rat model of Journal of Ophthalmology bilateral common carotid artery occlusion (BCCAO) [4]
CCHinduced reduction in the artery and vein diameter was statistically significant (p < 0 05). This decrease was not significantly altered by the administration of osthole-PI, aspirin, and ginaton whereas osthole-IG-induced reversal of vessel diameter was significant which was similar to the values in the control group (Figure 1(b))
Summary
Chronic cerebral hypoperfusion (CCH) can lead to cognitive impairment and neuronal cell damage, via oxidative stress and inflammation [1]. Carotid artery stenosis (CAS) is currently the most common cause of CCH, and the degree of CAS and its effect on Willis ring directly determine the symptoms of cerebral ischemia. The ophthalmic artery is the first major branch of the internal carotid artery, and CAS has a direct effect on ocular hemodynamics. This causes slow or even reversed flow in ocular vessels. We previously reported that the Rho/ MAPK/iNOS pathway was involved in chronic RI, leading to tissue inflammation and apoptosis in a rat model of Journal of Ophthalmology bilateral common carotid artery occlusion (BCCAO) [4]. We analyzed the effectiveness of different methods of osthole administration, in comparison to aspirin and ginaton, in a rat model of CCH
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
