Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens

Arjunan, Pachiappan; Swaminathan, Radhika; Yuan, Jessie; Elashiry, Mohamed M.; Tawfik, Amany; Al‐Shabrawey, Mohamed; Martin, Pamela M.; Thangaraju, Muthusamy; Cutler, Christopher W.

doi:10.3390/antiox10020309

Cited by 5 publications

(5 citation statements)

References 128 publications

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“…Ligature-induced periodontitis with P. gingivalis infection also showed aggravation of age-related macular degeneration. An increase in mRNA expression related to oxidative stress, angiogenesis, and pro-inflammatory mediators in the retinae was observed, whereas antioxidant and anti-inflammatory-related gene expression was notably decreased [110]. Periodontitis increased mRNA expression of TNF-α and IL-1β in the kidneys.…”

Section: Other Disease Model Mice With Ligature-induced Periodontitismentioning

confidence: 93%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

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Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

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Section: Other Disease Model Mice With Ligature-induced Periodontitismentioning

confidence: 93%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

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“…The host–pathogen interaction and the strategies by which RPE cells respond to the monomicrobial or polymicrobial biofilm and its pathological impact in vitro and in vivo has remained elusive. Consecutively, the same team has demonstrated a role for periodontal pathogens in the augmentation of the AMD phenotype in vivo by employing a groundbreaking AMD + PD murine model [ 69 ]. This report identified particularly the role of the keystone periodontopathogen Pg in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina.…”

Section: Eye Diseases Associated With Oral Pathogensmentioning

confidence: 99%

“…They have also identified augmented expression of oxidative stress, angiogenesis, and pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes were notably declined. Further, interestingly, the key finding of the study documented is the expression of Pg and its fimbrial 16s-rRNA gene in the AMD + PD mice retinae [ 69 , 71 ]. Given this setting, the authors postulate that upon stimulation by the dysbiotic oral pathogens or through systemic diffusion of their metabolic by-products, the inflammatory immune cells may function as potential carriers of the oral pathogens and disseminate them to distant body sites including the immune-privileged sites such as the eye.…”

Section: Eye Diseases Associated With Oral Pathogensmentioning

confidence: 99%

“…Arjunan et al in an in vitro study characterized Porphyromonas gingivalis (Pg) invasion in the human RPE cells and its prolonged survival by autophagy evasion within the RPE cells [ 70 ]. Another in vivo study employing a pioneering AMD + PD murine model demonstrated the role of periodontal infection in the augmentation of AMD phenotype [ 69 ]). Fusobacterium and Rothia species were identified as risk factors in the AMD by Pockpa et al, [ 72 ] and Rullo et al, [ 42 ], respectively.…”

Section: Figurementioning

confidence: 99%

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Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?

Arjunan

Swaminathan

2022

JCM

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Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.

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“…al. set out to develop a simple, reproducible model that emulates characteristics of both AMD and PD [ 17 ]. The authors evaluated the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis in the progression of laser-induced choroidal neovascularization (Li-CNV) in a mouse retina.…”

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confidence: 99%