Brief reports
MELAS A3243G mitochondrial DNA mutation and age related maculopathy

https://doi.org/10.1016/j.ajo.2004.06.026Get rights and content

Purpose

To determine whether mitochondrial DNA mutations play a role in the development of age related maculopathy (ARM).

Design

Case report.

Methods

Hair follicles were collected from 3557 persons aged 49 years or older during the Blue Mountains Eye Study. General health measures were assessed and a detailed eye examination was performed, including stereo retinal photography of the macula, and other retinal fields. ARM was graded according to international classification. Polymerase chain reaction and restriction fragment length polymorphism analysis was performed to detect the MELAS A3243G mutation in 570 subjects identified to have signs of Early or Late ARM, as well as in age- and gender-matched controls.

Results

Only one participant with Early ARM, mild hearing loss, hypertension, ischemic heart disease, and asthma was found to have the MELAS A3243G mutation.

Conclusions

The MELAS A3243G mutation appears to be a very rare cause of typical ARM in the general population.

Cited by (26)

  • Effects of ozone repeated short exposures on the airway/lung inflammation, airway hyperresponsiveness and mucus production in a mouse model of ovalbumin-induced asthma

    2018, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    It is a major and increasing global health problem that affects about 300 million patients worldwide currently [2–4]. High concentrations of ozone are associated with the increases in mortality, hospitalizations, and emergency-department visit rates of asthmatics [5–7]. Notably, compared with non-asthmatic patients, the decrements of forced expiratory volume in one second(FEV1) and the increases of airway responsiveness are more significant in asthmatics following high concentration ozone exposure (0.4 ppm, 2 h) [8,9].

  • Mitochondrial dysfunction underlying outer retinal diseases

    2017, Mitochondrion
    Citation Excerpt :

    The syndromes MELAS and MIDD are mostly caused by a m.3243A > G mutation in mtDNA and are associated with variable degrees of retinal pigment abnormalities, RPE atrophy and hyperpigmentation. Moreover, RPE anomalies were proportional to an overall disease severity and to a higher degree of mutation load in mtDNA (Rummelt et al., 1993; Massin et al., 1999; Michaelides et al., 2008; Daruich et al., 2014; Jones et al., 2004). The ocular manifestations of MELAS are characterized by pigmentary retinopathy, external ophthalmoplegia, optic atrophy, macular pattern dystrophy, degeneration of photoreceptor outer segments in the macula, ptosis and posterior cataract, all leading to severe vision loss.

  • Aging is not a disease: Distinguishing age-related macular degeneration from aging

    2013, Progress in Retinal and Eye Research
    Citation Excerpt :

    Loss of the RPE's key role as homeostatic agent in the retina throws the entire system out of balance. Of note, patients with the MELAS A to G 3243 mtDNA point mutation have pigmentary changes in the macula similar to those seen in AMD (Sue et al., 1997), though very few AMD cases feature this mutation (Jones et al., 2004). Classical regulators of cell proliferation and differentiation include the MAPK and PI3K/Akt signaling pathways (Chang and Karin, 2001; Manning and Cantley, 2007).

  • Consequences of oxidative stress in age-related macular degeneration

    2012, Molecular Aspects of Medicine
    Citation Excerpt :

    Of note, the expression level of OGG1 (the major repair enzyme against oxidative DNA lesions) decreases by almost half in AMD macular RPE cells compared to aged macular RPE cells, suggesting that reduced levels of this protein in AMD (Lin et al., 2011b). Furthermore, a genetic component of mitochondrial stress appears to be in play as pigmentary abnormalities and RPE atrophy similar to those present in early AMD are detected in 75% of individuals with the A3243G MELAS mitochondrial DNA mutation (Jones et al., 2004). Intriguingly, certain mtDNA haplogroups have been reported to be associated with either increased or decreased prevalence of age-related maculopathy (Jones et al., 2007).

  • Mitochondrial DNA damage and its potential role in retinal degeneration

    2008, Progress in Retinal and Eye Research
    Citation Excerpt :

    There is strong evidence for mitochondrial dysfunction being involved in AMD. Retinal pigmentary abnormalities and RPE atrophy similar to those present in the early AMD phenotype are detected in 75% of individuals with the A3243G MELAS mitochondrial DNA mutation (Jones et al., 2004). Retinal pigmentary changes have also been observed in other systemic diseases caused by specific mtDNA defects such as Kearns–Sayre syndrome, Chronic Progressive External Ophthalmoplegia, and LHON (Isashiki et al., 1998).

View all citing articles on Scopus

Supported by the Australian National Health & Medical Research Council, Canberra, Australia (Grant Nos. 211069 & 991407).

View full text