Advances in glaucoma genetics

Sakurada, Yoichi; Mabuchi, Fumihiko

doi:10.1016/bs.pbr.2015.04.006

Cited by 21 publications

(17 citation statements)

References 97 publications

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“…Very little is known about the function of the proteins that these genes encode, nor do we know whether they are expressed early in foetal human retina. The fact that variants of ATOH7 could be associated with glaucoma (reviewed by Sakurada and Mabuchi, 2015) highlights how early variations in retina development may eventually lead to retinal diseases later in life. In this context, the pigeon retina could prove to be a useful new model system with which to uncover some of the intricate mechanisms underlying growth and neurogenesis in the macula of primates.…”

Section: Discussionmentioning

confidence: 99%

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity

et al. 2016

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The macula and fovea located at the optical centre of the retina make primate visual perception unique among mammals. Our current understanding of retina ontogenesis is primarily based on animal models having no macula and no fovea. However, the pigeon retina and the human macula share a number of structural and functional properties that justify introducing the former as a new model system for retina development. Comparative transcriptome analysis of pigeon and chicken retinas at different embryonic stages reveals that the genetic programmes underlying cell differentiation are postponed in the pigeon until the end of the period of cell proliferation. We show that the late onset of neurogenesis has a profound effect on the developmental patterning of the pigeon retina, which is at odds with the current models of retina development. The uncoupling of tissue growth and neurogenesis is shown to result from the fact that the pigeon retinal epithelium is inhibitory to cell differentiation. The sum of these developmental features allows the pigeon to build a retina that displays the structural and functional traits typical of primate macula and fovea.

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Section: Discussionmentioning

confidence: 99%

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity

et al. 2016

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“…The TM plays a vital role in actively maintaining homeostatic IOP and its dysfunction is widely accepted as the main causative factor for hypertensive glaucoma 1,2,19 . A number of single nucleotide polymorphisms in several genes identified by GWAS analysis have been linked to increased glaucoma risk and increased resistance to AH outflow facility at the TM; however, the precise molecular mechanisms that give rise to this disease are not yet fully understood 21,22,23,24,25 . Genetic mouse models can provide a powerful tool for studying the molecular mechanisms of glaucoma.…”

Section: Discussionmentioning

confidence: 99%

“…However, the molecular mechanisms associated with TM dysfunction and how it regulates AH drainage are not yet fully understood and is currently a major focus of glaucoma research 1,2,19,20 . While several genome-wide association studies (GWAS) have linked a number of genes to glaucoma and increased resistance to AH outflow facility at the TM, the exact molecular mechanisms that lead to disease are not yet fully understood 21,22,23,24,25 .…”

Section: Introductionmentioning

confidence: 99%

Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis

Sutherland

Wang

Brown

et al. 2018

JoVE

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Laser capture microdissection (LCM) has allowed gene expression analysis of single cells and enriched cell populations in tissue sections. LCM is a great tool for the study of the molecular mechanisms underlying cell differentiation and the development and progression of various diseases, including glaucoma. Glaucoma, which comprises a family of progressive optic neuropathies, is the most common cause of irreversible blindness worldwide. Structural changes and damage within the trabecular meshwork (TM) can result in increased intraocular pressure (IOP), which is a major risk factor for developing glaucoma. However, the precise molecular mechanisms involved are still poorly understood. The ability to perform gene expression analysis will be crucial in obtaining further insights into the function of these cells and its role in the regulation of IOP and glaucoma development. To achieve this, a reproducible method for isolating highly enriched TM from frozen sections of mouse eyes and a method for downstream gene expression analysis, such as RT-qPCR and RNA-Seq is needed. The method described herein is developed to isolate highly pure TM from mouse eyes for downstream digital PCR and microarray analysis. In addition, this technique can be easily adapted for the isolation of other highly enriched ocular cells and cell compartments that have been difficult to isolate from mouse eyes. The combination of LCM and RNA analysis can contribute to a more comprehensive understanding of the cellular events underlying glaucoma.

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“…In addition to clinical risk factors, genetic risk factors for glaucoma have been established through the Mendelian studies and genome-wide association studies (GWAS) ( Cioffi and American Academy of Ophthalmology 2014 ; Mabuchi et al. 2015 ; Sakurada and Mabuchi 2015 ; Wiggs 2015 ; Wiggs et al. 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA Normative Aging Study

Wang

Moroi

Bakulski

et al. 2018

Environ Health Perspect

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Background:Oxidative stress may play an important role in the etiology of primary open-angle glaucoma (POAG). The association between risk of POAG and lead exposure, which is an environmental source of oxidative stress, has not been fully investigated yet.Objective:Our objective was to determine the association between bone lead—a biomarker of cumulative lead dose (tibia lead) or an endogenous source of stored lead (patella lead)—and incident POAG.Methods:We examined a prospective cohort of 634 POAG-free men [mean baseline age=66.8 y of age (SD=6.7)] from the Normative Aging Study (NAS) who had tibia and patella K X-ray fluorescence lead measurements between 1 January 1991 and 31 December 1999. They also had standard ocular evaluations by NAS optometrists until 31 December 2014. POAG cases were identified by consistent reports of enlarged or asymmetric cup-to-disc ratio together with visual field defect or existence of disc hemorrhage. We used Cox proportional hazards regressions to estimate hazard ratios (HRs) of incident POAG and adjusted survival curves to examine changes in the risk of POAG during follow-up according to bone lead quartiles.Results:We identified 44 incident cases of POAG by the end of follow-up (incidence rate=74 per 10,000 person-years; median follow-up=10.6 y). In fully adjusted models, 10-fold increases in patella lead and tibia lead were associated with HRs of 5.06 (95% CI: 1.61, 15.88, p=0.005) and 3.07 (95% CI: 0.94, 10.0, p=0.06), respectively. The HRs comparing participants in the third and fourth quartiles with the lowest quartile were 3.41 (95% CI: 1.34, 8.66) and 3.24 (95% CI: 1.22, 8.62) for patella lead (p-for-trend=0.01), and 3.84 (95% CI: 1.54, 9.55) and 2.61 (95% CI: 0.95, 7.21) for tibia lead (p-for-trend=0.02).Conclusions:Our study provides longitudinal evidence that bone lead may be an important risk factor for POAG in the U.S. population. https://doi.org/10.1289/EHP3442

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Advances in glaucoma genetics

Cited by 21 publications

References 97 publications

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity

Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis

Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA Normative Aging Study

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