Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration
A critical target in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from the disruption of intercellular tight junctions (TJs). A Connexin43 (Cx43)-based peptide, aCT1, has been sh...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022026470 |
| _version_ | 1798014454786424832 |
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| author | Elisabeth Obert Christina Grek Gautam Ghatnekar Bärbel Rohrer |
| author_facet | Elisabeth Obert Christina Grek Gautam Ghatnekar Bärbel Rohrer |
| author_sort | Elisabeth Obert |
| collection | DOAJ |
| description | A critical target in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from the disruption of intercellular tight junctions (TJs). A Connexin43 (Cx43)-based peptide, aCT1, has been shown to prevent VEGF-induced loss of transepithelial resistance, choroidal neovascularization (CNV) and RPE-cell damage via the stabilization of TJs. Here, we probe the relative efficacies of aCT1 alone, anti-VEGF alone, and aCT1 with anti-VEGF in treating AMD pathologies. aCT1 monotherapy administered as topical eye drops with and without a VEGF blocking antibody administered systemically was tested in a mouse model of laser-induced CNV. The CNV mouse is the standard neovascular AMD model, reproducing hallmarks of its pathology. CNV lesion size and fluid accumulation were assessed using optical coherence tomography. During the angiogenesis phase of CNV lesion development, single applications of anti-VEGF or aCT1 reduced lesion and fluid dome size equally. The combinatorial aCT1/anti-VEGF strategy demonstrated lack of additive effects in this model. These data suggest that TJ stabilization by aCT1 is effective in ameliorating RPE dysfunction in a model of AMD-like angiogenesis, and that this strategy is as effective as the current clinical standard of care, anti-VEGF therapy. Critically, aCT1 holds potential as a new neovascular AMD treatment that can be administered using eye drops, which is preferable to the intravitreal injections required for standard anti-VEGF therapy. |
| first_indexed | 2024-04-11T15:18:33Z |
| format | Article |
| id | doaj.art-d3b0c80133574fbaba220dde1ebfa626 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T15:18:33Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d3b0c80133574fbaba220dde1ebfa6262022-12-22T04:16:26ZengElsevierHeliyon2405-84402022-11-01811e11359Evaluation of a connexin-based peptide for the treatment of age-related macular degenerationElisabeth Obert0Christina Grek1Gautam Ghatnekar2Bärbel Rohrer3Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United StatesXequel Bio, Inc., Mount Pleasant, SC 29464, United StatesRegranion, LLC, Mount Pleasant, SC 29464, United StatesDepartment of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, United States; Ralph H. Johnson VA Medical Center, Charleston, SC 29401, United States; Corresponding author.A critical target in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from the disruption of intercellular tight junctions (TJs). A Connexin43 (Cx43)-based peptide, aCT1, has been shown to prevent VEGF-induced loss of transepithelial resistance, choroidal neovascularization (CNV) and RPE-cell damage via the stabilization of TJs. Here, we probe the relative efficacies of aCT1 alone, anti-VEGF alone, and aCT1 with anti-VEGF in treating AMD pathologies. aCT1 monotherapy administered as topical eye drops with and without a VEGF blocking antibody administered systemically was tested in a mouse model of laser-induced CNV. The CNV mouse is the standard neovascular AMD model, reproducing hallmarks of its pathology. CNV lesion size and fluid accumulation were assessed using optical coherence tomography. During the angiogenesis phase of CNV lesion development, single applications of anti-VEGF or aCT1 reduced lesion and fluid dome size equally. The combinatorial aCT1/anti-VEGF strategy demonstrated lack of additive effects in this model. These data suggest that TJ stabilization by aCT1 is effective in ameliorating RPE dysfunction in a model of AMD-like angiogenesis, and that this strategy is as effective as the current clinical standard of care, anti-VEGF therapy. Critically, aCT1 holds potential as a new neovascular AMD treatment that can be administered using eye drops, which is preferable to the intravitreal injections required for standard anti-VEGF therapy.http://www.sciencedirect.com/science/article/pii/S2405844022026470Retinal pigment epitheliumTight junctionsChoroidal neovascularizationVascular endothelial growth factorAge-related macular degenerationaCT1 |
| spellingShingle | Elisabeth Obert Christina Grek Gautam Ghatnekar Bärbel Rohrer Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration Heliyon Retinal pigment epithelium Tight junctions Choroidal neovascularization Vascular endothelial growth factor Age-related macular degeneration aCT1 |
| title | Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration |
| title_full | Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration |
| title_fullStr | Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration |
| title_full_unstemmed | Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration |
| title_short | Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration |
| title_sort | evaluation of a connexin based peptide for the treatment of age related macular degeneration |
| topic | Retinal pigment epithelium Tight junctions Choroidal neovascularization Vascular endothelial growth factor Age-related macular degeneration aCT1 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022026470 |
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