Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma?

Hollands, Hussein; Johnson, Davin; Hollands, Simon; Simel, David L.; Jinapriya, Delan; Sharma, Sanjay

doi:10.1001/jama.2013.5099

Cited by 127 publications

(92 citation statements)

References 77 publications

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“…These results indicate that a positive family history of glaucoma in patients with POAG reflects the influence of genetic variants predisposing to POAG. The present study supports the findings of previous reports [1][2][3][4][5][6] showing that a positive family history of glaucoma is a risk factor for POAG and suggests that genetic factors rather than familial factors may be considered to play important roles in the pathogenesis of POAG. Moreover, we investigated the associations between genetic variants predisposing to POAG and the number or degree of relatives with glaucoma.…”

Section: The Present Study Demonstrated a High Prevalencesupporting

confidence: 92%

“…Clinically, intraocular pressure (IOP) elevation and myopia are reported to be risk factors for optic nerve damage in patients with POAG. 1 However, the underlying causes of these risk factors also remain obscure. Additionally, a positive family history of glaucoma is a major risk factor for POAG, 1-6 and genetic and/or familial factors are therefore considered to play important roles in the pathogenesis of POAG.…”

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confidence: 99%

“…12 Genetic analyses, including genomewide association studies, have identified approximately 65 (candidate) genetic variants predisposing to POAG, 13 which can be classified into 2 types. One type involves genetic variants associated with IOP elevation (IOP-related genetic variant), while the other involves genetic variants associated with vulnerability of the RGC and/or optic nerve independent of IOP (non-IOPrelated genetic variant), which may include genetic variants associated with the apoptosis of RGCs, 14 myopia, 1 and optic nerve circulation. 15 POAG is clinically classified into high-tension glaucoma (HTG), in which an elevated IOP is the major feature, and normal-tension glaucoma (NTG), in which the IOP is consistently within the statistically normal range for the population, and it is presumed that IOP-related genetic variants would predominate in patients with HTG.…”

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confidence: 99%

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Involvement of Genetic Variants Associated With Primary Open-Angle Glaucoma in Pathogenic Mechanisms and Family History of Glaucoma

Mabuchi

Sakurada

Kashiwagi

et al. 2015

American Journal of Ophthalmology

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Section: The Present Study Demonstrated a High Prevalencesupporting

confidence: 92%

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confidence: 99%

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confidence: 99%

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Involvement of Genetic Variants Associated With Primary Open-Angle Glaucoma in Pathogenic Mechanisms and Family History of Glaucoma

Mabuchi

Sakurada

Kashiwagi

et al. 2015

American Journal of Ophthalmology

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“…One important point is that glaucoma is a complex disease resulting from the confluence of various factors. [27][28][29][30][31][32]43,44 To fill the gap between glaucoma patients and animal disease models, 45 we are currently investigating GLAST gene abnormalities in glaucoma patients.…”

Section: -37mentioning

confidence: 99%

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

et al. 2013

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Dedicator of cytokinesis 3 (Dock3), a new member of the guanine nucleotide exchange factors for the small GTPase Rac1, promotes axon regeneration following optic nerve injury. In the present study, we found that Dock3 directly binds to the intracellular C-terminus domain of NR2B, an N-methyl-D-aspartate (NMDA) receptor subunit. In transgenic mice overexpressing Dock3 (Dock3 Tg), NR2B expression in the retina was significantly decreased and NMDA-induced retinal degeneration was ameliorated. In addition, overexpression of Dock3 protected retinal ganglion cells (RGCs) from oxidative stress. We previously reported that glutamate/aspartate transporter (GLAST) is a major glutamate transporter in the retina, and RGC degeneration due to glutamate neurotoxicity and oxidative stress is observed in GLAST-deficient (KO) mice. In GLAST KO mice, the NR2B phosphorylation rate in the retina was significantly higher compared with Dock3 Tg:GLAST KO mice. Consistently, glaucomatous retinal degeneration was significantly improved in GLAST KO:Dock3 Tg mice compared with GLAST KO mice. These results suggest that Dock3 overexpression prevents glaucomatous retinal degeneration by suppressing both NR2B-mediated glutamate neurotoxicity and oxidative stress, and identifies Dock3 signaling as a potential therapeutic target for both neuroprotection and axonal regeneration.

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“…myocilin | CRISPR | glaucoma | trabecular meshwork | genome editing G laucoma is a multifactorial disease, with increased intraocular pressure (IOP) as a major risk factor (1,2). With the advent of efficient genome editing tools, it is now reasonable to think that the genomic component of glaucoma can be targeted for therapeutic and prophylactic purposes.…”

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confidence: 99%

CRISPR-Cas9–based treatment of myocilin-associated glaucoma

Jain

Zode

Kasetti

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

155

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Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-offunction mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9-mediated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease.myocilin | CRISPR | glaucoma | trabecular meshwork | genome editing

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Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma?

Cited by 127 publications

References 77 publications

Involvement of Genetic Variants Associated With Primary Open-Angle Glaucoma in Pathogenic Mechanisms and Family History of Glaucoma

Involvement of Genetic Variants Associated With Primary Open-Angle Glaucoma in Pathogenic Mechanisms and Family History of Glaucoma

Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

CRISPR-Cas9–based treatment of myocilin-associated glaucoma

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