Topical Administration of Peroxiredoxin-6 on the Cornea Suppresses Inflammation and Neovascularization Induced by Ultraviolet Radiation

Shi, Hui; Yu, H J; Wang, Hai Yan; Wang, Wen Ting; Jin, Shao Hua; Zhu, Ping; Li, Shi Jia; Cheng, Rong; Li, Jian Yuan

doi:10.1167/iovs.12-10064

Cited by 24 publications

(21 citation statements)

References 48 publications

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“…PRDX6 has been shown to play an important role during inflammatory processes, and, according to data from a recent study (41), topically administered PRDX6 maintained the homeostasis of corneal cells, reducing inflammation and suppressing neovascularization and apoptosis, induced by ultraviolet irradiation. Inflammation is a main factor leading to diabetes and its associated complications (19).…”

Section: Discussionmentioning

confidence: 95%

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Pacifici

Arriga

Sorice³

et al. 2014

Diabetes

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Enhanced oxidative stress contributes to the pathogenesis of diabetes and its complications. Peroxiredoxin 6 (PRDX6) is a key regulator of cellular redox balance, with the peculiar ability to neutralize peroxides, peroxynitrite, and phospholipid hydroperoxides. In the current study, we aimed to define the role of PRDX6 in the pathophysiology of type 2 diabetes (T2D) using PRDX6 knockout (2/2) mice. Glucose and insulin responses were evaluated respectively by intraperitoneal glucose and insulin tolerance tests. Peripheral insulin sensitivity was analyzed by euglycemic-hyperinsulinemic clamp, and molecular tools were used to investigate insulin signaling. Moreover, inflammatory and lipid parameters were evaluated. We demonstrated that PRDX6 2/2 mice developed a phenotype similar to early-stage T2D caused by both reduced glucose-dependent insulin secretion and increased insulin resistance. Impaired insulin signaling was present in PRDX6 2/2 mice, leading to reduction of muscle glucose uptake. Morphological and ultrastructural changes were observed in islets of Langerhans and livers of mutant animals, as well as altered plasma lipid profiles and inflammatory parameters. In conclusion, we demonstrated that PRDX6 is a key mediator of overt hyperglycemia in T2D glucose metabolism, opening new perspectives for targeted therapeutic strategies in diabetes care.A large body of evidence supports a pivotal role for oxidative stress in the etiopathogenesis of insulin resistance (IR) and diabetes (1). Oxidative stress is characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defense systems. Among all body tissues, pancreatic b-cells are very sensitive to oxidative stress because of their low expression of antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (2). Moreover, hyperglycemia by itself induces IR, increasing oxidative stress injuries, which lead to overt type 2 diabetes (T2D) (3). Interestingly, a relatively new family of antioxidant proteins, the peroxiredoxins (PRDXs), is more highly expressed in pancreatic b-cells (4). Among the six members of this non-seleno peroxidase family, PRDX6 is present in the cytoplasm and is unique because it has peroxidase and also phospholipase A 2 activity (5). Several findings demonstrate the importance of PRDX6 in maintaining redox homeostasis, as follows: lack of PRDX6, in fact, increases the susceptibility to oxidative stress in different tissues (6,7). Nevertheless, data on the relationship between PRDX6 and the pathogenesis of IR and T2D are not available (8). Therefore, we hypothesized that, in terms of physiological status, PRDX6 may play a role in the etiology of IR and diabetes conditions through tissue redox levels. In the current study, we tested our hypothesis in a model of PRDX6 knockout mice (PRDX6 2/2). RESEARCH DESIGN AND METHODS Animal ModelsC57BL/6J wild-type (WT) mice weighing 18-20 g were obtained from The Jackson Laboratory (Bar Harbor, ME), while PRDX6 2/2 mice of mixed background (C57BL6/129SvJ)...

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Section: Discussionmentioning

confidence: 95%

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Pacifici

Arriga

Sorice³

et al. 2014

Diabetes

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“…It has been demonstrated that the topical administration of this protein had inhibitory effect on VEGF expression, inflammation, and suppressed neovascularization and apoptosis in ultraviolet irradiated rat corneas [26]. The presence of proteins involved in the metabolism of reactive oxygen species, such as peroxiredoxins and catalase in the normal tear film [27] suggests their function in the defense against these highly reactive and toxic compounds.…”

Section: Peroxiredoxin-6mentioning

confidence: 99%

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Ihnatko

Edén

Lagali

et al. 2013

Journal of Proteomics

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Aniridia is a rare congenital genetic disorder caused by haploinsuffiency of the PAX6 gene, the master gene for development of the eye. The expression of tear proteins in aniridia is unknown. To screen for proteins involved in the aniridia pathophysiology, the tear fluid of patients with diagnosed congenital aniridia was examined using two-dimensional electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two-dimensional map of tear proteins in aniridia has been established and 7 proteins were differentially expressed with P less than 0.01 between aniridia patients and control subjects. Five of them were more abundant in healthy subjects, particularly alpha-enolase, peroxiredoxin 6, cystatin S, gelsolin, apolipoprotein A-1 and two other proteins, zinc-alpha 2-glycoprotein and lactoferrin were more expressed in the tears of aniridia patients. Moreover, immunoblot analysis revealed elevated levels of vascular endothelial growth factor (VEGF) in aniridia tears which is in concordance with clinical finding of pathological blood and lymph vessels in the central and peripheral cornea of aniridia patients. The proteins with different expression in patients tears may be new candidate molecules involved in the pathophysiology of aniridia and thus may be helpful for development of novel treatment strategies for the symptomatic therapy of this vision threatening condition. Biological significance This study is first to demonstrate protein composition and protein expression in aniridic tears and identifies proteins with different abundance in tear fluid from patients with congenital aniridia vs. healthy tears

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“…Patients with UV-induced photokeratitis exhibit promoted apoptosis of corneal cells due to inflammatory response, induction of reactive oxygen species (ROS), and damage to the cell membrane and deoxyribonucleic acid (dNA) (6). Treatment, including the topical administration of peroxiredoxin-6, has been reported to promote recovery from UV-induced corneal injury after 14 weeks (7). chemical burns and exposure to UVB lead to corneal injury, which can be aggravated by inflammatory responses, oxidative stress and neovascularization, resulting in blindness (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Exposure to UV lasers can result in pathology to the cornea, lens or retina of the primate eye (10). Specifically, irradiation of the eyes with UV causes serious enzymatic disturbances and inflammatory reactions in the cornea (7). chronic exposure to UVR causes damage to the anterior pole of the eye, such as pterygium or photokeratitis, which is accompanied by several corneal disorders, including inflammatory infiltration and CNV (11).…”

Section: Introductionmentioning

confidence: 99%

Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation‑induced corneal neovascularization

Han

Wang

et al. 2019

Int J Mol Med

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Topical Administration of Peroxiredoxin-6 on the Cornea Suppresses Inflammation and Neovascularization Induced by Ultraviolet Radiation

Abstract: The topically administered PRDX6 maintained the homeostasis of corneal cells, reduced inflammation, and suppressed neovascularization and apoptosis under ultraviolet irradiation.

Cited by 24 publications

References 48 publications

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation‑induced corneal neovascularization

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