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.
Highlights
High myopia, defined as myopia exceeding 26.00 diopters or axis length $ 26 mm, is a disorder that affects almost the entire human eye, from the anterior pole to the posterior pole
High myopia can be associated with high refractive errors, cataract, open-angled glaucoma, and retinopathy, all of which are recognized as significant problems of subspecialties related to ophthalmology [1], and more difficulties are encountered during surgery in such cases
As the incidence of high myopia is much higher in Asia than elsewhere [2], it is likely that high-myopic cataract (HMC) is more common in Asia [3]
Summary
High myopia, defined as myopia exceeding 26.00 diopters or axis length $ 26 mm, is a disorder that affects almost the entire human eye, from the anterior pole to the posterior pole. Several population-based studies [3,4,5,6] have examined the association between high myopia and cataract. Data from the Blue Mountains Eye Study [4] suggested that high myopia is associated with both nuclear and posterior subcapsular cataract. In another series of studies [2,7], it was reported that nuclear cataract is strongly associated with high-axial myopia. Praveen et al [7] reported that cataract density is higher in patients with high myopia than in other groups of patients. High myopia is not associated with posterior subcapsular or cortical cataract
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