Evaluation of Pigment Epithelium–Derived Factor and Complement Factor I Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes

Miyake, Masahiro; Yamashiro, Kenji; Nakanishi, Hideo; Nakata, Isao; Akagi-Kurashige, Yumiko; Kumagai, Kyoko; Oishi, Maho; Tsujikawa, Akitaka; Moriyama, Muka; Ohno‐Matsui, Kyoko; Mochizuki, Manabu; Yoshimura, Nagahisa

doi:10.1167/iovs.13-12280

Cited by 25 publications

(18 citation statements)

References 33 publications

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“…To investigate the association between WNT7B rs10453441 and extreme myopia, we performed two association tests. In these analyses, we defined extremely myopic patients as patients whose average axial lengths in both eyes were 428.00 mm, according to a previous report 9 . Samples whose average axial lengths ranged from 22.00 to 24.00 mm were used as control samples.…”

Section: Methodsmentioning

confidence: 99%

“…Disruption of this coordination causes refractive errors, such as myopia and hyperopia 6,7 . Of these components, axial length plays a major role in refraction; therefore, in clinical settings, the degree of myopia is predominantly determined by axial length [8][9][10] . A recent large-scale, genome-wide meta-analysis by the Consortium for Refractive Error and Myopia (CREAM) reported that 23 of 29 loci associated with refraction were also associated with axial length 11,12 .…”

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confidence: 99%

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Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

et al. 2015

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Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, P meta ¼ 3.9 Â 10 À 13 ) and corneal curvature (P meta ¼ 2.9 Â 10 À 40 ) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR) meta ¼ 1.13, P meta ¼ 0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

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Section: Methodsmentioning

confidence: 99%

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Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

et al. 2015

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“…[1]–[4] Myopic eyes with very long axial lengths (≥26.0 mm, ≥26.5 mm, or ≥28.0 mm) or a high degree of myopic refractive error (≤−5D, ≤−6D, or ≤−8D) are classified as highly myopic. [5]–[11] High myopia is typically associated with excessive elongation of the globe and, in middle-aged individuals, often leads to pathological changes such as posterior staphyloma. [12], [13] Moriyama et al analyzed the shapes of eyes with pathologic myopia using three-dimensional magnetic resonance imaging (MRI).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Fundus Shape in Highly Myopic Eyes by Using Curvature Maps Constructed from Optical Coherence Tomography

et al. 2014

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PurposeTo evaluate fundus shape in highly myopic eyes using color maps created through optical coherence tomography (OCT) image analysis.MethodsWe retrospectively evaluated 182 highly myopic eyes from 113 patients. After obtaining 12 lines of 9-mm radial OCT scans with the fovea at the center, the Bruch’s membrane line was plotted and its curvature was measured at 1-µm intervals in each image, which was reflected as a color topography map. For the quantitative analysis of the eye shape, mean absolute curvature and variance of curvature were calculated.ResultsThe color maps allowed staphyloma visualization as a ring of green color at the edge and as that of orange-red color at the bottom. Analyses of mean and variance of curvature revealed that eyes with myopic choroidal neovascularization tended to have relatively flat posterior poles with smooth surfaces, while eyes with chorioretinal atrophy exhibited a steep, curved shape with an undulated surface (P<0.001). Furthermore, eyes with staphylomas and those without clearly differed in terms of mean curvature and the variance of curvature: 98.4% of eyes with staphylomas had mean curvature ≥7.8×10−5 [1/µm] and variance of curvature ≥0.26×10−8 [1/µm].ConclusionsWe established a novel method to analyze posterior pole shape by using OCT images to construct curvature maps. Our quantitative analysis revealed that fundus shape is associated with myopic complications. These values were also effective in distinguishing eyes with staphylomas from those without. This tool for the quantitative evaluation of eye shape should facilitate future research of myopic complications.

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“…This result indicated that abnormal metabolism rather than the decrease in PEDF synthesis might be correlated with myopia development. The genetic background of the occurrence of CNV secondary to high myopia was explored [100]. There might be a possible association between the PEDF SNP rs12603825 and the occurrence of myopic CNV.…”

Section: Pedf Levels In Patients With Cnv Secondary To Pathological Mmentioning

confidence: 99%

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

2020

Oxidative Medicine and Cellular Longevity

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Choroidal neovascularization (CNV) is a sight-threatening disease and is characterized by the formation of pathological neovascularization in the choroid which extends into the subretinal space. Exudative age-related macular degeneration (AMD) is the formation of CNV in the macular area which leads to irreversible blindness. Continuous leakage and hemorrhage of the CNV lesion may eventually result in scarring or later fibrosis, which could result in photoreceptor cell atrophy. The current strategy for treating CNV is the use of antivascular endothelial growth factor (VEGF) agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF therapy. Other studies have also reported the side effects of single anti-VEGF treatment. And long-term inhibition of a single system may result in collateral damage to other visual elements. Pigment epithelium-derived factor (PEDF) is a 50 kDa protein that was first isolated from the conditioned medium of human RPE cells. PEDF has both antiangiogenesis and neuroprotective functions for photoreceptor cells. It may be a potential ocular antiangiogenic agent. This review outlines the distribution of PEDF in the eye, the mechanism of antiangiogenesis, the protective effect on the retina, and the relationship between PEDF and VEGF.

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Evaluation of Pigment Epithelium–Derived Factor and Complement Factor I Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes

Abstract: We demonstrated a marginal association of the PEDF SNP, rs12603825, with myopic CNV in extremely myopic patients. A further study using a larger cohort might elucidate a significant association; rs1136287 in CFI is less likely to be associated in Japanese individuals.

Cited by 25 publications

References 33 publications

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Analysis of Fundus Shape in Highly Myopic Eyes by Using Curvature Maps Constructed from Optical Coherence Tomography

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

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