Epigenetics and Ocular Diseases: From Basic Biology to Clinical Study

Yan, Biao; Yao, Jin; Tao, Zhi‐Fu; Jiang, Qin

doi:10.1002/jcp.24522

Cited by 26 publications

(18 citation statements)

References 118 publications

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“…Epigenetic marks may be modified by environmental exposures [43] and consequently provide a mechanistic link between environmental risk factors and the etiology of diseases. It has been postulated that epigenetic changes might partially explain the late onset and progressive nature of some ocular diseases such as macular degeneration and glaucoma [44, 45], which are not fully explained by known mutations. The same may be true in late-onset FECD where the disease is manifest late in life and a single causative gene mutation has not yet been identified.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy

et al. 2017

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Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

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Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy

et al. 2017

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“…In addition, the CHOP could promote cell death by the induction of miR-708, which is known to regulate the expression of many genes, including the rhodopsin. Perhaps, the miR-708 is elevated in aged retinas, and might be responsible for the reduction in the RHO found in aged retinas in addition to age-related photoreceptor cell loss [31] and potential epigenetic changes [28, 40]. …”

Section: Discussionmentioning

confidence: 99%

Unfolded protein response is activated in aged retinas

Lenox

Bhootada

Gorbatyuk

et al. 2015

Neuroscience Letters

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An unfolded protein response (UPR) in addition to oxidative stress and the inflammatory response is known to be activated in age-related ocular disorders, such as macular degeneration, diabetic retinopathy, glaucoma, and cataracts. Therefore, we aimed to investigate whether healthy aged retinas display UPR hallmarks, in order to establish a baseline for the activated UPR markers for age-related ocular diseases. Using western blotting, we determined that the hallmarks of the UPR PERK arm, phosphorylated (p) eIF2a, ATF4, and GADD34, were significantly altered in aged vs. young rat retinas. The cleaved pATF6 (50) and CHOP proteins were dramatically upregulated in the aged rodent retinas, indicating the activation of the ATF6 UPR arm. The UPR activation was associated with a drop in rhodopsin expression and in the NRF2 and HO1 levels, suggesting a decline in the anti-oxidant defense in aged retinas. Moreover, we observed down-regulation of anti-inflammatory IL-10 and IL-13 and upregulation of pro-inflammatory RANTES in the healthy aged retinas, as measured using the Bio-plex assay. Our results suggest that cellular homeostasis in normal aged retinas is compromised, resulting in the concomitant activation of the UPR, oxidative stress, and inflammatory signaling. This knowledge brings us closer to understanding the cellular mechanisms of the age-related retinopathies and ocular disorders characterized by an ongoing UPR, and highlight the UPR signaling molecules that should be validated as potential therapeutic targets.

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“…However, the potential role of lncRNAs in CN is still unknown. 11 In this study, corneal neovascularization in C57BL/6 mice was induced by alkaline cauterization of the central cornea. We performed lncRNA expression profiling and compared the differences in lncRNA expression between normal and vascularized corneas.…”

mentioning

confidence: 99%