MTHFR C677T Homozygous Mutation in a Patient with Pigmentary Glaucoma and Central Retinal Vein Occlusion

Jaksic, Vesna; Markovic, Vujica; Milenković, S; Stefanovic, Ivan; Jakovic, Natalija; Knežević, Miloš

doi:10.1159/000272023

Cited by 10 publications

(9 citation statements)

References 48 publications

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“…These data correlate with the ganglion cell losses noted here in cbs +/− mice and reported earlier (Ganapathy et al ., 2009; Ganapathy et al ., 2011). Within the past few years there have been several clinical studies reporting elevated homocysteine associated with various forms of glaucoma (Tranchina et al ., 2011; Turgut et al ., 2010; Jaksic et al ., 2010; Micheal et al ., 2009; Clement et al ., 2009). It will be informative to determine whether mutations of CBS and genes encoding other proteins involved in homocysteine metabolism contribute to some forms of glaucoma or optic nerve dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…This reduction was not progressive, however, and no difference was noted when mice were tested at 13 weeks of age. Although VEPs were not recorded, it is important to note that several cases of MTHFR mutations and visual defects associated with diabetic retinopathy, anterior ischemic optic neuropathy and glaucoma have been reported (Maeda et al ., 2006; Felekis et al ., 2010; Jaksic et al ., 2010). …”

Section: Discussionmentioning

confidence: 99%

“…In patient-based studies, elevated homocysteine has been detected in a number of clinical conditions affecting the eye, including AMD (Axer-Siegel et al , 2004; Seddon et al, 2006); maculopathy and retinal degeneration (Tsina et al , 2005); primary and secondary open-angle glaucoma (Bleich et al , 2002); exfoliative glaucoma (Vessani et al , 2003), pigmentary glaucoma (Jaksic et al , 2010 ), proliferative vitreoretinopathy (Aydemir et al , 2008), type 2 diabetes mellitus (Yang et al, 2002), central retinal vein occlusion (Lahey et al , 2003). Poloschek et al (2005) reported abnormal electroretinograms (ERGs) and visual evoked potentials (VEPs) in a child with severe hyperhomocysteinemia due to methionine synthase deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

Sturgill-Short

Ganapathy

et al. 2012

Experimental Eye Research

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Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs−/−) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs+/−) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs−/− (3 weeks) and cbs−+/− mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wildtype (WT) littermates. Light- and dark-adapted ERGs were recorded along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs−/− mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs+/− mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs+/− mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs+/− mice at 15 and 30 weeks. The later onset of functional defects in cbs+/− mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs+/− mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in modest and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

Sturgill-Short

Ganapathy

et al. 2012

Experimental Eye Research

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“…In most of these cases, CRVO occurs without the presence of the typical risk factors, and a comprehensive workup is warranted [2]. Unusual causes for CRVO in young patients include hypercoagulability states, collagen vascular diseases, lymphoproliferative disorders, malignant hypertension, medications (most notably oral contraceptives and isotretinoin), and trauma [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]. A recent study has demonstrated that hyperlipidemia and hyperhomocysteinemia were the most significant risk factors for CRVO in patients under 40 [14].…”

Section: Introductionmentioning

confidence: 99%

Intense Exercise Causing Central Retinal Vein Occlusion in a Young Patient: Case Report and Review of the Literature

Moisseiev¹,

Sagiv

Lazar³

2014

Case Rep Ophthalmol

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We report a 19-year-old patient who developed a central retinal vein occlusion (CRVO) with significant macular edema and visual impairment following intense exercise and dehydration. The patient was treated with 3 intravitreal bevacizumab injections with complete resolution. A review of the literature on the cause and treatment for CRVO in young patients was performed, focusing on the role of intense exercise and dehydration as a rare pathogenesis mechanism of CRVO.

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“…For example, ectopia lentis is a major ocular manifestation in homocystinuria. 2 A number of pathological conditions affecting retina have also been linked to hyperhomocysteinemia, such as glaucoma (primary and secondary open-angle glaucoma, exfoliation glaucoma, pigmentary glaucoma), [3][4][5] macular degeneration, maculopathy and retinal degeneration, [6][7][8] and diabetic retinopathy. 9,10 Elevated plasma homocysteine is a potential risk factor for the development of premature occlusive atherosclerosis in humans 2 ; and clinical investigations provide strong evidence that hyperhomocysteinemia is a risk factor for retinal vascular diseases, including central retinal vein occlusion, branch retinal vein occlusion, and central retinal artery occlusion.…”

mentioning

confidence: 99%

Alterations of Retinal Vasculature in Cystathionine-Beta-Synthase Mutant Mice, a Model of Hyperhomocysteinemia

Tawfik

Al‐Shabrawey

Roon³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Mice with moderate/severe hyperhomocysteinemia due to deficiency or absence of the cbs gene encoding cystathionine-beta-synthase (CBS) have marked retinal disruption, ganglion cell loss, optic nerve mitochondrial dysfunction, and ERG defects; those with mild hyperhomocysteinemia have delayed retinal morphological/functional phenotype. Excess homocysteine is a risk factor for cardiovascular diseases; however, it is not known whether excess homocysteine alters retinal vasculature. METHODS. Cbs, and cbs À/À mice (age~3 weeks) were subjected to angiography; retinas were harvested for cryosections, flat-mount preparations, or trypsin digestion and subjected to immunofluorescence microscopy to visualize vessels using isolectin-B4, to detect angiogenesis using anti-VEGF and anti-endoglin (anti-CD105) and activated glial cells (anti-glial fibrillary acidic protein [anti-GFAP]) and to investigate the blood-retinal barrier using the tight junction markers zonula occludens-1 (ZO-1) and occludin. Expression RESULTS. Angiography revealed vascular leakage in cbs À/À mice; immunohistochemical analysis demonstrated vascular patterns consistent with ischemia; isolectin-B4 labeling revealed a capillary-free zone centrally and new vessels with capillary tufts midperipherally. This was associated with increased vegf mRNA and protein, CD105, and GFAP in cbs À/À retinas concomitant with a marked decrease in ZO-1 and occludin. Homocysteine-treated HRECs showed increased permeability.CONCLUSIONS. Severe elevation of homocysteine in cbs À/À mutant mice is accompanied by alterations in retinal vasculature (ischemia, neovascularization, and incompetent bloodretinal barrier). The marked disruption of retinal structure and decreased visual function reported in cbs À/À mice may reflect vasculopathy as well as neuropathy. (Invest Ophthalmol Vis Sci. 2013;54:939-949)

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MTHFR C677T Homozygous Mutation in a Patient with Pigmentary Glaucoma and Central Retinal Vein Occlusion

Cited by 10 publications

References 48 publications

Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

Intense Exercise Causing Central Retinal Vein Occlusion in a Young Patient: Case Report and Review of the Literature

Alterations of Retinal Vasculature in Cystathionine-Beta-Synthase Mutant Mice, a Model of Hyperhomocysteinemia

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