A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

Lin, Phoebe; McClintic, Scott M.; Nadeem, Urooba; Skondra, Dimitra

doi:10.3390/jcm10102072

Cited by 24 publications

(14 citation statements)

References 68 publications

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“…Finally, when investigating characteristics of microglia, the influence of microbiomes should be considered. Not only age-related neurodegenerative diseases but also retinal diseases such as AMD are now being associated with microglial pathologies that may be influenced by changes in the gut microbiome 54 – 56 . Additionally, a plethora of environmental factors such as diet and geographic location may influence this gut microbiome 57 .…”

Section: Discussionmentioning

confidence: 99%

Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms

Choi¹,

Hill²,

Guo³

et al. 2022

Sci Rep

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The resident macrophages of the central nervous system, microglia, are becoming increasingly implicated as active participants in neuropathology and ageing. Their diverse and changeable morphology is tightly linked with functions they perform, enabling assessment of their activity through image analysis. To better understand the contributions of microglia in health, senescence, and disease, it is necessary to measure morphology with both speed and reliability. A machine learning approach was developed to facilitate automatic classification of images of retinal microglial cells as one of five morphotypes, using a support vector machine (SVM). The area under the receiver operating characteristic curve for this SVM was between 0.99 and 1, indicating strong performance. The densities of the different microglial morphologies were automatically assessed (using the SVM) within wholemount retinal images. Retinas used in the study were sourced from 28 healthy C57/BL6 mice split over three age points (2, 6, and 28-months). The prevalence of ‘activated’ microglial morphology was significantly higher at 6- and 28-months compared to 2-months (p < .05 and p < .01 respectively), and ‘rod’ significantly higher at 6-months than 28-months (p < 0.01). The results of the present study propose a robust cell classification SVM, and further evidence of the dynamic role microglia play in ageing.

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Section: Discussionmentioning

confidence: 99%

Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms

Choi¹,

Hill²,

Guo³

et al. 2022

Sci Rep

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“…A synergistic link between genetic predispositions and environmental factors, such as high-fat diet and severity of AMD, has been described. 43 , 44 In the past few years investigators have looked more closely into the possible role of the gut microbiome in the pathogenesis of AMD.…”

Section: Discussionmentioning

confidence: 99%

Gnotobiotic Operations and Assembly for Development of Germ-Free Animal Model of Laser-Induced Choroidal Neovascularization

Movahedan

Barba

Spedale

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose Compelling new evidence reveals a close link between the gut microbiome and the pathogenesis of neovascular age-related macular degeneration (nAMD). Germ-free (GF) animal models are the current gold standard for studying host the microbe interactions in vivo; yet, no GF animal models of nAMD are available today. This protocol describes gnotobiotic operations and assembly for a laser-induced choroidal neovascularization (CNV) model in GF mice to study the gut microbiome in neovascular AMD. Methods We developed a step-wise approach to performing retinal laser photocoagulation in GF C57BL/6J mice that were bred and maintained at the gnotobiotic facility. Following a strict sterility protocol, we administered laser photocoagulation via an Argon 532-nm laser attached to a customized slit-lamp delivery system. Sterility was confirmed by weekly fecal cultures and reverse transcriptase–polymerase chain reaction. Results The experiment was repeated twice at different time points using seven mice (14 eyes). Stool cultures and RT-PCR remained negative for 14 days post-procedure in all mice. Lectin immunostaining performed on choroidal flatmounts confirmed the presence of CNV lesions 2 weeks after laser treatment. Conclusions We established a GF mouse model of nAMD with detailed guidelines to deliver retinal laser in GF mice maintaining sterility after the laser procedure. Translational Relevance To our knowledge, this is the first protocol that describes a GF murine model of laser-induced CNV. In addition to nAMD, this animal model can be used to investigate host–microbial interactions in other eye diseases with laser-induced mouse models such as glaucoma and retinal vein occlusion.

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“…AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Besides, microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis, thus providing a novel potential therapeutic target [28, 120].…”

Section: Gut Microbiota and Nutritional Factorsmentioning

confidence: 99%

Pathophysiology of Age-Related Macular Degeneration: Implications for Treatment

et al. 2022

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Age-related macular degeneration (AMD) is a complex, multifactorial, progressive retinal disease that affects millions of people worldwide and has become the leading cause of visual impairment in developed countries. The disease etiopathogenesis is not understood fully, although many triggers and processes that lead to dysfunction and degeneration of the retinal pigment epithelium (RPE) already have been identified. Thus, the lack of cellular control of oxidative stress, altered proteostasis, dysfunction of lipid homeostasis, and mitochondrial dysfunction form an internal feedback loop that causes the RPE to fail and allows accumulation of abnormal misfolded proteins and abnormal lipids that will form drusen. An inadequate antioxidant response, deficits in autophagy mechanisms, and dysregulation of the extracellular matrix (ECM) help to increase the deposition of abnormal drusen material over time. The drusen then act as inflammatory centers that trigger chronic inflammation of the subretinal space in which microglia and recruited macrophages also are involved, and the complement system is a key component. Choriocapillaris degeneration and nutritional influences are also classic elements recognized in the AMD pathophysiology. The genetic component of the disease is embodied in the recognition of the described risk or protective polymorphisms of some complement (mainly complement factor H, CFH) and ECM related genes (mainly age-related maculopathy susceptibility 2/high-temperature requirement protein A1, ARMS2/HTRA1). Carriers of the risk haplotype at ARMS2/HTRA1 have a higher risk of developing late AMD at a younger age. Finally, gut microbiota and epigenetics may play a role in modulating the progression to advanced AMD with the presence of local inflammatory conditions. Because of multiple implicated processes, different complex combinations of treatments will probably be the best option to obtain the best visual results; they in turn will differ depending on the type and spectrum of disease affecting individual patients or the disease stage in each patient at a specific moment. This will undoubtedly lead to personalized medicine for control and hopefully a future cure, which necessitates the continued unraveling of all the processes involved in the pathogenesis of AMD that must be understood to devise the combinations of treatments for different concurrent or subsequent problems.

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A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

Cited by 24 publications

References 68 publications

Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms

Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms

Gnotobiotic Operations and Assembly for Development of Germ-Free Animal Model of Laser-Induced Choroidal Neovascularization

Pathophysiology of Age-Related Macular Degeneration: Implications for Treatment

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