Abstract
Purpose Retinal ischemia is a medical condition associated with numerous retinal vascular disorders, such as age-related macular degeneration, glaucoma, and diabetic retinopathy. This in vitro cell and in vivo animal study investigated not only the protective effect of S-allyl L-cysteine (SAC, an active component of garlic) against retinal ischemia but also its associated protective mechanisms. Methods Retinal ischemia was mimicked by raising the intraocular pressure to 120 mmHg for 1 hour in one eye. The effects of pre-/postischemic administration of vehicle vs. SAC 0.18 mg vs. SAC 0.018 mg vs. SAC 0.0018 mg treatments on retina cells were evaluated through cellular viability (MTT assay), flash electroretinograms (ERGs), and fluorogold retrograde labelling (retinal ganglion cell (RGC) counting). Also, protein immunoblot was utilized to assess the role of Wnt, hypoxia inducible factor (HIF)-1α, and vascular endothelium factor (VEGF) in the proposed anti-ischemic mechanism. Lastly, the safety of drug consumption was investigated for changes in the animal's body weight, ERG waves, and blood biochemical parameters (e.g., glucose levels). Results The characteristic ischemic changes including significant reduction in ERG b-wave ratio and RGC number were significantly counteracted by pre- and postischemic low dose of SAC. Additionally, ischemia-induced overexpression of Wnt/HIF-1α/VEGF protein was ameliorated significantly by preischemic low dose of SAC. In terms of the animal safety, no significant body weight and electrophysiological differences were observed among defined different concentrations of SAC without following ischemia. In low SAC dosage and vehicle groups, various blood biochemical parameters were normal; however, high and medium concentrations of SAC significantly lowered the levels of uric acid, Hb, and MCHC. Conclusion This study shows that preischemic administration of low SAC dosage has been proved to be safe and most effective against rat retinal ischemia electrophysiologically and/or histopathologically. Moreover, counteracting the ischemia-induced overexpression of Wnt/HIF-1α/VEGF might presently explain SAC's anti-ischemic mechanism.
Highlights
Common retinal ischemic disorders include central/branch retinal artery occlusion, central/branch retinal vein occlusion, glaucoma, diabetic retinopathy, and neovascular agerelated macular degeneration. ese diseases are associated with visual impairment and even blindness in more severe cases
Other studies have shown that the canonical Wnt signaling enhances the expression of hypoxia induced factor-1α (HIF-1α), which increases vascular endothelial growth factor (VEGF) levels in hypoxia [7,8,9,10,11,12]
To test the optimal and safe cellular concentration of fortified S-allyl L-cysteine (SAC) onOGD-insulted cells, lower (0.1, 0.3, and 0.5 mM) and higher (1, 10, and 100 mM) concentrations of pre-Oxygen Glucose Deprivation (OGD) administration of SAC were tested and compared against the control group
Summary
Common retinal ischemic disorders include central/branch retinal artery occlusion, central/branch retinal vein occlusion, glaucoma, diabetic retinopathy, and neovascular agerelated macular degeneration. ese diseases are associated with visual impairment and even blindness in more severe cases. Ere are important Wnt pathway-mediated developmental retinal ischemic diseases that include diabetic retinopathy, familial exudative vitreoretinopathy, and persistent hyperplastic primary vitreous [2,3,4,5,6]. Evidence-Based Complementary and Alternative Medicine e current knowledge is that the canonical Wnt pathway is said to stabilize β-catenin expression. Liu et al have indicated that β-catenin can work with lymphoid enhancer-binding factor 1, in order to regulate the target gene expression as vascular endothelial growth factor (VEGF) [3]. Other studies have shown that the canonical Wnt signaling enhances the expression of hypoxia induced factor-1α (HIF-1α), which increases VEGF levels in hypoxia [7,8,9,10,11,12]. Our previous studies have mentioned that overexpression of Wnt pathway plays a pathogenic role of Norries disease and that blockage of Wnt pathway has been beneficial in its treatment [13]
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