Vjmv

02.12.2017 1 Comments

Abstract Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. Human genetic mapping studies have identified over 24 chromosomal loci linked to myopia [ 15 , 25 — 30 ]. Furthermore, mouse studies revealed that lack of Aplp2 has a dose-dependent suppressive effect on susceptibility to form-deprivation myopia, providing a potential gene-specific target for therapeutic intervention to treat myopia. Functional analysis of APLP2 using an APLP2 knockout mouse model confirmed functional significance of APLP2 in refractive development and implicated a potential role of synaptic transmission at the level of glycinergic amacrine cells of the retina for the development of myopia. Myopia is the most common vision disorder worldwide [ 3 ].

Vjmv


Epidemiological data suggest that common myopia represents a major risk factor for a number of potentially blinding ocular diseases such as cataract, glaucoma, retinal detachment, and myopic maculopathy, which is comparable to the risks associated with hypertension for stroke and myocardial infarction, and represents one of the leading causes of blindness [ 10 — 12 ]. Functional analysis of APLP2 using an APLP2 knockout mouse model confirmed functional significance of APLP2 in refractive development and implicated a potential role of synaptic transmission at the level of glycinergic amacrine cells of the retina for the development of myopia. Received Feb 10; Accepted Jul 7. Here, we present genetic and functional evidence identifying amyloid beta A4 precursor-like protein 2 APLP2 , which was previously found to be involved in synaptic plasticity and transmission in the central nervous system [ 36 — 52 ], as one such myopia-susceptibility gene. Here, gene set enrichment analysis GSEA [ 54 , 55 ] of these data revealed that expression of one of these genes, APLP2, among others was strongly associated with the refractive error phenotype. We found that a low-frequency risk allele of APLP2 confers susceptibility to myopia only in children exposed to large amounts of daily reading, thus, providing an experimental example of the long-hypothesized gene-environment interaction between nearwork and genes underlying myopia. Abstract Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development. Failure to achieve or maintain emmetropia leads to the development of refractive errors, i. Author Summary Gene variants identified by GWAS studies to date explain only a small fraction of myopia cases because myopia represents a complex disorder thought to be controlled by dozens or even hundreds of genes. Refractive eye development is controlled by both environmental and genetic factors [ 14 — 17 ]. It is estimated that 2. However, the currently-identified variants account for only a small fraction of myopia cases [ 31 ] suggesting the existence of a large number of yet unidentified low-frequency or small-effect variants, which underlie the majority of myopia cases [ 32 — 35 ]. However, genetic factors are believed to play a key role in determining the impact of environmental factors on refractive eye development, including populations that have experienced rapid rises in the prevalence of myopia in recent decades [ 14 — 18 ]. Human genetic mapping studies have identified over 24 chromosomal loci linked to myopia [ 15 , 25 — 30 ]. Results Genetic variation at the APLP2 locus is associated with myopia in children and adults In a previous study designed to identify genes differentially expressed in myopic eyes, we performed large-scale gene expression profiling in the retina of green monkeys Chlorocebus aethiops with experimentally induced myopia and identified differentially expressed genes [ 53 ]. Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Furthermore, mouse studies revealed that lack of Aplp2 has a dose-dependent suppressive effect on susceptibility to form-deprivation myopia, providing a potential gene-specific target for therapeutic intervention to treat myopia. Myopia is the most common vision disorder worldwide [ 3 ]. This article has been cited by other articles in PMC. The emmetropization process is regulated by a vision-driven feedback loop in the retina and downstream signaling cascades in other ocular tissues, and normally results in sharp vision emmetropia.

Vjmv


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