Role of Choline in Ocular Diseases

Hwang, Jung Hee; Shin, Young-Joo

doi:10.3390/ijms22094733

Cited by 16 publications

(11 citation statements)

References 134 publications

(178 reference statements)

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“…Interestingly, the photoreceptor cells of the retina have high affinity for choline and require an abundance of phospholipids to maintain the large membranous surface area of the outer segment [49][50][51] . Choline availability has also been linked to retinal degeneration [52][53][54] . Further confirming our results, the connection between FLVCR1 and choline was recently described as a metabolite quantitative trait loci association in nonagenarians and centenarians 55 .…”

Section: Discussionmentioning

confidence: 99%

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

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Genome-wide association studies (GWAS) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis associating serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) - a plasma membrane protein - and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells and in mice strongly impairs choline metabolism due to a block in choline import. Consistently, CRISPR-based genetic screens identified several components of the membrane phospholipid machinery as synthetic lethal with FLVCR1 loss. Finally, cells lacking FLVCR1 exhibit mitochondrial defects and upregulate the integrated stress response (ISR) through heme regulated inhibitors kinase (HRI). Altogether, these findings identify FLVCR1 as a universal mediator of choline transport in mammals and provide a platform to discover substrates for unknown metabolite transporters.

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Section: Discussionmentioning

confidence: 99%

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

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“…In the retina, a choline deficiency is associated with a distorted differentiation of retinal neuronal cells and cytoarchitectural defects. Moreover, increased phosphatidyl-choline levels are linked to lowered risks of diabetes and cardiovascular diseases [ 42 ].…”

Section: Results and Data Interpretationmentioning

confidence: 99%

Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities — preliminary data for PPPM validation

Kropp

Clerck

et al. 2023

EPMA Journal

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Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this “domino effect”. Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the “diagnostic tree” (yes/no) applicable to healthrisk assessment in diabetes care.

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“…Moreover, during cellular and tissue repair processes after trauma or corneal surgery, GPC plays an important role in proliferating and migrating epithelial cells (increases membrane fluidity) and plays an important role as an adjuvant and biological modulator of the neuroreparation of the epithelial nerve endings. Integrating the axons in the healing process promotes the synthesis of phospholipids and sphingolipids of the neuronal membranes of the nerve endings [ 20 – 22 ]. Second, Dexpanthenol (Dxp) is a biologically active alcohol-analog of pantothenic acid (PA) converted into PA inside the cell.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Glycerylphosphorylcholine and D-Panthenol Eye Drops in Patients Undergoing Cataract Surgery

Martone

Balestrazzi

Ciprandi

et al. 2022

Journal of Ophthalmology

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Cataract surgery is widespread. The surgical procedure is associated with damage to the epithelial barrier and interruption of the corneal innervation. In addition, pathological events sustain signs and symptoms that may persist for a long time. Recently, a fixed combination of alpha-glycerylphosphorylcholine and D-Panthenol (Oftassiale) has been available as eye drops. The present study investigated the effects of an Oftassiale therapy in 20 patients undergoing cataract surgery. A comparison group included 20 patients treated with topical hyaluronic acid. Standard prophylactic and anti-inflammatory treatment was prescribed to all patients. Clinical signs and symptoms were assessed over time. In vivo confocal microscopy (IVCM) was performed accordingly. Oftassiale treatment significantly reduced clinical features and improved IVCM outcomes. In addition, therapy was well-tolerated, and no clinically significant adverse events occurred. In conclusion, this study confirmed that IVCM helps assess the tunnel after cataract surgery due to its ability to provide microscopic details in vivo. Topical therapy with alpha-glycerylphosphorylcholine and D-Panthenol eye drops promoted and stabilized the reepithelialization process. This fixed combination also accelerated and modulated the repair of the corneal innervation. Moreover, this treatment was well-tolerated and safe.

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Role of Choline in Ocular Diseases

Cited by 16 publications

References 134 publications

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities — preliminary data for PPPM validation

Alpha-Glycerylphosphorylcholine and D-Panthenol Eye Drops in Patients Undergoing Cataract Surgery

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