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      • Record: found
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      Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice

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      Author(s): 1 , 2 , 1 , 1 , 1 , 2 , 2 , 1 , 3 , 2 , 3 , 4 , 3 , 5 , 5 , 2 , 1 , 1 ,
      Publication date (Electronic):
      Journal: Investigative Ophthalmology & Visual Science
      Publisher: The Association for Research in Vision and Ophthalmology
      Keywords: neovascular age-related macular degeneration (nAMD), saccharin, artificial sweetener (AS), modifiable risk factors, intravitreal anti-VEGF treatment, treatment need, systems biology, saccharin, choroidal neovascularization (CNV), inflammation, VEGF, complement factors

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          Abstract

          Purpose

          We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment.

          Methods

          In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line.

          Results

          Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity ( P = 0.004) and those without subretinal hyper-reflective material ( P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas ( P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation ( P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 ( TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression.

          Conclusions

          Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

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          Most cited references42

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          The biology of VEGF and its receptors.

          Napoleone Ferrara, Hans-Peter Gerber, Jennifer LeCouter (2003)
          Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.
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            Age-related macular degeneration

            Paul Mitchell, Gerald Liew, Bamini Gopinath … (2018)
            Age-related macular degeneration is a leading cause of visual impairment and severe vision loss. Clinically, it is classified as early-stage (medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic). Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids). Progression from early-stage to late-stage disease can be slowed with high-dose zinc and antioxidant vitamin supplements. Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab, aflibercept, or bevacizumab) is highly effective at treating neovascular age-related macular degeneration, and has markedly decreased the prevalence of visual impairment in populations worldwide. Currently, no proven therapies for atrophic disease are available, but several agents are being investigated in clinical trials. Future progress is likely to be from improved efforts in prevention and risk-factor modification, personalised medicine targeting specific pathways, newer anti-vascular endothelial growth factor agents or other agents, and regenerative therapies.
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              Age-related macular degeneration.

              Laurence Lim, Paul Mitchell, Johanna Seddon … (2012)
              Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Invest Ophthalmol Vis Sci
                Journal ID (iso-abbrev): Invest Ophthalmol Vis Sci
                Journal ID (publisher-id): IOVS
                Title: Investigative Ophthalmology & Visual Science
                Publisher: The Association for Research in Vision and Ophthalmology
                ISSN (Print): 0146-0404
                ISSN (Electronic): 1552-5783
                Publication date (Electronic): 01 April 2024
                Publication date Collection: April 2024
                Volume: 65
                Issue: 4
                Electronic Location Identifier: 5
                Affiliations
                [1 ]Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt–Universität zu Berlin, Department of Ophthalmology, Hindenburgdamm 30, Berlin, Germany
                [2 ]Experimental Ophthalmology, Department of Ophthalmology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität, Berlin Institute of Health, Humboldt-University, Berlin, Germany
                [3 ]Alacris Theranostics, Max-Planck-Straße 3, Berlin, Germany
                [4 ]Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Quebec, Canada
                [5 ]Max-Planck-Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin, Germany
                Author notes
                [* ]Correspondence: Oliver Zeitz, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt–Universität zu Berlin, Department of Ophthalmology, Hindenburgdamm 30, Berlin 12203, Germany; oliver.zeitz@ 123456charite.de .
                Article
                Publisher ID: IOVS-23-38501
                DOI: 10.1167/iovs.65.4.5
                PMC ID: 10996979
                PubMed ID: 38558091
                SO-VID: 4aa4577f-1df4-407c-a984-6ef7e06e415b
                Copyright © Copyright 2024 The Authors
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date accepted : 11 February 2024
                Date received : 17 September 2023
                Page count
                Pages: 13
                Categories
                Subject: Biochemistry and Molecular Biology
                Subject: Biochemistry and Molecular Biology

                Keywords: neovascular age-related macular degeneration (namd),saccharin,artificial sweetener (as),modifiable risk factors,intravitreal anti-vegf treatment,treatment need,systems biology,choroidal neovascularization (cnv),inflammation,vegf,complement factors
                Data availability:
                Keywords: neovascular age-related macular degeneration (namd), saccharin, artificial sweetener (as), modifiable risk factors, intravitreal anti-vegf treatment, treatment need, systems biology, choroidal neovascularization (cnv), inflammation, vegf, complement factors

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