Single Nucleotide Polymorphism (rs7543472) in EPHA2 gene is associated with Age-related Cataract in subjects enrolled from Multan in Southern Punjab: a case-control study

Aslam, Sana; Khosa, Tafheem; Akbar, Atif; Latif, Muhammad; Chaudhary, Muhammad Ajmal; Shaikh, Rehan Sadiq

doi:10.5455/jpma.6232

Cited by 3 publications

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“…Epha2 participates in the complex, global patterning of lens fiber cells, which is necessary for maximal optical quality (Zhou and Shiels, 2018). Common variants in EPHA2 showed significant association with cortical cataract, such as rs7543472 and rs3754334 (Yang et al, 2013, Aslam et al, 2020. Previous studies mostly focused on the single nucleotide polymorphism of EphA2 in ARC.…”

Section: Discussionmentioning

confidence: 99%

EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells

Liu²,

Wang

et al. 2021

Genet. Mol. Biol.

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Age-related cataract (ARC) is a progressive lens opacification that occurs from middle to old age. Eph-receptor tyrosinekinase-type A2 (EphA2) has been reported to be associated with ARC. This work aims to investigate the molecular mechanism of EphA2 in ARC. We treated human lens epithelial cells (SRA01/04) with different concentration of H 2 O 2 to induce lens epithelial cell damage. Then, we found that H 2 O 2 treatment significantly suppressed cell viability and enhanced the expression of EphA2 in the SRA01/04 cells. H 2 O 2 treatment repressed cell viability and enhanced the levels of reactive oxygen species (ROS) in SRA01/04 cells, which was partly abolished by EphA2 up-regulation. Moreover, EphA2 overexpression reduced H 2 O 2 -induced apoptosis of SRA01/04 cells. EphA2 up-regulation caused an up-regulation of Bcl-2, and repressed the expression of Bax and Cleaved-caspase-3 in the SRA01/04 cells following H 2 O 2 treatment. In conclusion, our data confirm that EphA2 overexpression enhances cell viability and inhibits apoptosis in the H 2 O 2 -treated SRA01/04 cells, thereby reducing H 2 O 2 -induced damage of lens epithelial cells. Thus, this work provides new insights into the mechanism of EphA2 in ARC.

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Section: Discussionmentioning

confidence: 99%

EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells

Liu²,

Wang

et al. 2021

Genet. Mol. Biol.

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Cell-based Therapy for Ocular Disorders: A Promising Frontier

Ahani-Nahayati

Niazi

Moradi

et al. 2022

CSCR

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: As the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for application in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding mesenchymal stem/stromal cells (MSC), neural stem cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and retinal pigment epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard, in the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from age-related macular degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the in vivo reports published during the last decade.

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Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis

Murugan

Cheng

2022

Front. Cell Dev. Biol.

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The eye lens is responsible for fine focusing of light onto the retina, and its function relies on tissue transparency and biomechanical properties. Recent studies have demonstrated the importance of Eph-ephrin signaling for the maintenance of life-long lens homeostasis. The binding of Eph receptor tyrosine kinases to ephrin ligands leads to a bidirectional signaling pathway that controls many cellular processes. In particular, dysfunction of the receptor EphA2 or the ligand ephrin-A5 lead to a variety of congenital and age-related cataracts, defined as any opacity in the lens, in human patients. In addition, a wealth of animal studies reveal the unique and overlapping functions of EphA2 and ephrin-A5 in lens cell shape, cell organization and patterning, and overall tissue optical and biomechanical properties. Significant differences in lens phenotypes of mouse models with disrupted EphA2 or ephrin-A5 signaling indicate that genetic modifiers likely affect cataract phenotypes and progression, suggesting a possible reason for the variability of human cataracts due to Eph-ephrin dysfunction. This review summarizes the roles of EphA2 and ephrin-A5 in the lens and suggests future avenues of study.

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Single Nucleotide Polymorphism (rs7543472) in EPHA2 gene is associated with Age-related Cataract in subjects enrolled from Multan in Southern Punjab: a case-control study

Cited by 3 publications

References 0 publications

EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells

EphA2 overexpression reduces H2O2-induced damage of lens epithelial cells

Cell-based Therapy for Ocular Disorders: A Promising Frontier

Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis

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