Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens
Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/2/309 |
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| author | Pachiappan Arjunan Radhika Swaminathan Jessie Yuan Mohamed Elashiry Amany Tawfik Mohamed Al-Shabrawey Pamela M. Martin Thangaraju Muthusamy Christopher W. Cutler |
| author_facet | Pachiappan Arjunan Radhika Swaminathan Jessie Yuan Mohamed Elashiry Amany Tawfik Mohamed Al-Shabrawey Pamela M. Martin Thangaraju Muthusamy Christopher W. Cutler |
| author_sort | Pachiappan Arjunan |
| collection | DOAJ |
| description | Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen <i>Porphyromonas gingivalis</i>, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected <i>Pg</i> and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory. |
| first_indexed | 2024-03-09T00:47:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T00:47:24Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-33c198dd02fc49d2a86a72832cf53b1e2023-12-11T17:26:16ZengMDPI AGAntioxidants2076-39212021-02-0110230910.3390/antiox10020309Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral PathogensPachiappan Arjunan0Radhika Swaminathan1Jessie Yuan2Mohamed Elashiry3Amany Tawfik4Mohamed Al-Shabrawey5Pamela M. Martin6Thangaraju Muthusamy7Christopher W. Cutler8Department of Periodontics, Dental College of Georgia, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta, GA 30912, USAVision Discovery Institute, Augusta University, Augusta, GA 30912, USAVision Discovery Institute, Augusta University, Augusta, GA 30912, USAVision Discovery Institute, Augusta University, Augusta, GA 30912, USADepartment of Biochemistry & Molecular Biology, Augusta University, Augusta, GA 30912, USADepartment of Periodontics, Dental College of Georgia, Augusta, GA 30912, USAEmerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen <i>Porphyromonas gingivalis</i>, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected <i>Pg</i> and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.https://www.mdpi.com/2076-3921/10/2/309age-related macular degenerationretinal inflammationoxidative stressantioxidantsretinal degenerationperiodontal disease |
| spellingShingle | Pachiappan Arjunan Radhika Swaminathan Jessie Yuan Mohamed Elashiry Amany Tawfik Mohamed Al-Shabrawey Pamela M. Martin Thangaraju Muthusamy Christopher W. Cutler Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens Antioxidants age-related macular degeneration retinal inflammation oxidative stress antioxidants retinal degeneration periodontal disease |
| title | Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens |
| title_full | Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens |
| title_fullStr | Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens |
| title_full_unstemmed | Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens |
| title_short | Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens |
| title_sort | exacerbation of amd phenotype in lasered cnv murine model by dysbiotic oral pathogens |
| topic | age-related macular degeneration retinal inflammation oxidative stress antioxidants retinal degeneration periodontal disease |
| url | https://www.mdpi.com/2076-3921/10/2/309 |
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