Abstract
Ischemia–reperfusion (I/R) injury is associated with numerous retinal diseases, such as diabetic retinopathy, acute glaucoma, and other vascular retinopathies. Hypercapnic acidosis (HCA) has a protective effect on lung, myocardial, and central nervous system ischemic injury models. However, no study has evaluated its protective effects in an experimental retinal I/R injury model. In this study, retinal I/R injury was induced in Sprague Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 minutes. HCA was induced before and after the injury. After 24 hours, the terminal dUTP nick end labeling assay was performed. Moreover, the ratios of cleaved caspase-3/total caspase-3, phosphorylated IκB/IκB, and phosphorylated p38 were measured through Western blotting. After 7 days, the rats’ aqueous humor was analyzed. In addition, electroretinography and retinal thickness measurement were performed in the rats. Moreover, the retinal neural cell line RGC-5 was exposed to 500 μM H2O2 for 24 hours to induce a sustained oxidative stress in vitro. The effects of HCA were evaluated by comparing oxidative stress, MAPK signals, NF-κB signals, survival rates, and apoptosis rates in the RGC-5 cells before and after H2O2 exposure. We further investigated whether the potent I/R-protective heat shock protein (HSP) 32 contribute to protective effects of HCA. Our results indicated that HCA has protective effects against retinal I/R injury both in vivo and in vitro, at multiple levels, including antiapoptotic, anti-inflammatory, antioxidative, and functional retinal cell protection. Further research clarifying the role of HCA in retinal I/R injury prevention and treatment is warranted.
Highlights
Retinal ischemia–reperfusion (I/R) injury is a well-known pathological hallmark associated with diabetic retinopathy, ophthalmic artery occlusion, retinal vessel occlusion, and acute glaucoma, all of which result in severe visual impairment and subsequent vision loss [1]
Compared with the IR group, the IR-Hypercapnic acidosis (HCA) group attenuated the protein concentration increase in the aqueous humor (5.94 ± 0.31 mg/mL; P < 0.05; Fig 1B). These findings suggest that HCA induction after I/R injury has anti-inflammatory effects in vivo
There was a significant increase of the ratio of cleaved caspase-3/caspase-3 in H2O2 groups compared with the control and post groups (Fig 4B and 4C).These findings revealed that HCA induction after H2O2 exposure had a protective effect against the H2O2-induced oxidative stress of RGC-5 cell apoptosis
Summary
Retinal ischemia–reperfusion (I/R) injury is a well-known pathological hallmark associated with diabetic retinopathy, ophthalmic artery occlusion, retinal vessel occlusion, and acute glaucoma, all of which result in severe visual impairment and subsequent vision loss [1]. The major cause of the damage during the second phase (i.e., the reperfusion period) is the initiation of the inflammatory cascade, including free-radical-mediated retinal neuronal cell degeneration, cytokine release, and leukocyte activation [2,3,4,5]. Determination of the mechanisms underlying retinal neural cell degeneration in I/R injury may facilitate the development of a treatment to protect the tissue against oxidative stress during reperfusion. We hypothesized that HCA reduces retinal I/R injury-induced inflammation and apoptosis. This study evaluated the HCA-induced anti-inflammatory effects, antioxidative effects, and apoptosis suppression in an experimental retinal I/R injury model and verified whether the potent I/R-protective HSP32 contribute to these protective effects of HCA
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