Epigenetic Regulation of αA-crystallin in High Myopia-Induced Dark Nuclear Cataract

Abstract

PurposeTo assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA).MethodsWe reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2–3; High-Myopic Cataract (HMC) NC2–3; ARC NC5–6; HMC NC5–6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry.ResultsThe odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98–6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5–6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2–3 and ARC NC2–3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5–6 Group were significantly lower than the ARC NC5–6 Group and high-myopic controls.ConclusionsHigh myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients.

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

“…Down-regulation of CRYAA via H19/miR-675 targeting reduces the expression of chaperones, which is able to bind to the denatured proteins induced by oxidative stress and thus preserve the transparency of the lens [57]. This may accelerate the oxidative modification of proteins in the nucleus, resulting in the pathogenesis of nuclear ARC [5,12].…”

“…Critical enzymes involved in DNA methylation, such as DNMT1 and MeCP2, have been identified in human lens epithelial cells (HLECs) [10,11]. Epigenetic regulatory processes, including DNA methylation of CRYAA [9,10,[12][13][14], histone acetylation of SOD1 [15] and long non-coding RNA (lncRNA)-MIAT and KCNQ1OT1 [16,17], have been implicated in the pathological cataractogenesis.…”

Effect of pupil size on higher-order aberrations in high-myopic pseudophakic eyes with posterior staphyloma

“…In the current study, with KR-1W analyzer, we measured the internal HOAs in pseudophakic highmyopic eyes with posterior staphyloma under different pupil sizes and found that posterior staphyloma might be the structure that offset the increased internal HOAs induced by mydriasis. On the basis of previous researches, 3,17,18 HM is of high prevalence in Asia, especially in China, and it affects people's visual function by large population both among children and adults. Relationship between HOAs and myopia is still under investigation.…”

DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes

“…Our previous study found that the promoter of the CRYAA gene, encoding a major structure protein, αA- crystallin, in the lens, is hypermethylated and hence downregulated in the lens of HMC patients, which could be one of the mechanisms that explains the higher severity of cataracts in highly myopic eyes [3], [9]. In addition to being a structural crystallin, αA- crystallin is also a molecular chaperone with a known function in preventing oxidative damages.…”