scholarly journals High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2119
Author(s):  
David Dao ◽  
Bingqing Xie ◽  
Urooba Nadeem ◽  
Jason Xiao ◽  
Asad Movahedan ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Enrichment Analysis ◽  
Retinal Disease ◽  
Vessel Diameter ◽  
Age Related Macular Degeneration ◽  
High Fat ◽  
Inhibitor Activity ◽  
Age Related ◽  
Fat Diets ◽  
Transcriptomic Changes

The relationship between retinal disease, diet, and the gut microbiome has shown increasing importance over recent years. In particular, high-fat diets (HFDs) are associated with development and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy. However, the complex, overlapping interactions between diet, gut microbiome, and retinal homeostasis are poorly understood. Using high-throughput RNA-sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) mice on a regular diet (ND) and HFD to investigate transcriptomic changes without influence of gut microbiome. After correction of raw data, 53 differentially expressed genes (DEGs) were identified, of which 19 were upregulated and 34 were downregulated in GF-HFD mice. Key genes involved in retinal inflammation, angiogenesis, and RPE function were identified. Enrichment analysis revealed that the top 3 biological processes affected were regulation of blood vessel diameter, inflammatory response, and negative regulation of endopeptidase. Molecular functions altered include endopeptidase inhibitor activity, protease binding, and cysteine-type endopeptidase inhibitor activity. Human and mouse pathway analysis revealed that the complement and coagulation cascades are significantly affected by HFD. This study demonstrates novel data that diet can directly modulate the retinal transcriptome independently of the gut microbiome.

scholarly journals Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration

Biology Open ◽  
2021 ◽  
Vol 10 (11) ◽  
Author(s):  
Dan Zhang ◽  
Doina M. Mihai ◽  
Ilyas Washington
Keyword(s):  
Vitamin A ◽  
Plexiform Layer ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Retinal Damage ◽  
Stargardt Disease ◽  
Root Cause ◽  
Age Related ◽  
Transcriptomic Changes

ABSTRACT In the most prevalent retinal diseases, including Stargardt disease and age-related macular degeneration (AMD), byproducts of vitamin A form in the retina abnormally during the vitamin A cycle. Despite evidence of their toxicity, whether these vitamin A cycle byproducts contribute to retinal disease, are symptoms, beneficial, or benign has been debated. We delivered a representative vitamin A byproduct, A2E, to the rat's retina and monitored electrophysiological, histological, proteomic, and transcriptomic changes. We show that the vitamin A cycle byproduct is sufficient alone to damage the RPE, photoreceptor inner and outer segments, and the outer plexiform layer, cause the formation of sub-retinal debris, alter transcription and protein synthesis, and diminish retinal function. The presented data are consistent with the theory that the formation of vitamin A byproducts during the vitamin A cycle is neither benign nor beneficial but may be sufficient alone to cause the most prevalent forms of retinal disease. Retarding the formation of vitamin A byproducts could potentially address the root cause of several retinal diseases to eliminate the threat of irreversible blindness for millions of people.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

2021 ◽  
Author(s):  
Yesa Yang ◽  
Hannah Dunbar
Keyword(s):  
Clinical Trial ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Age Related ◽  
Wide Range ◽  
Trial Endpoints ◽  
Visual Acuity Loss ◽  
Psychophysical Test ◽  
Trial Endpoint

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

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

2021 ◽  
Vol 10 (10) ◽  
pp. 2072
Author(s):  
Phoebe Lin ◽  
Scott M. McClintic ◽  
Urooba Nadeem ◽  
Dimitra Skondra
Keyword(s):  
Macular Degeneration ◽  
Intestinal Microbiota ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Age Related ◽  
Intestinal Dysbiosis ◽  
Apo E ◽  
Dry Amd

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.

Medical retina

2014 ◽  
pp. 515-592 ◽  
Author(s):  
Alastair K.O. Denniston ◽  
Philip I. Murray
Keyword(s):  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Cystoid Macular Oedema ◽  
Eye Disease ◽  
Anatomy And Physiology ◽  
Age Related ◽  
Clinical Presentations ◽  
Diabetic Eye Disease ◽  
Retinal Vascular Disease ◽  
Medical Retina

‘Medical retina’ provides the reader with a practical approach to the assessment and management of retinal disease. After outlining the relevant anatomy and physiology of this structure, the chapter addresses the key clinical presentations arising from retinal disease, notably age-related macular degeneration, diabetic eye disease, cystoid macular oedema, retinal vascular disease, and genetic retinal disease. Using a patient-centred approach the key clinical features, investigations and treatment (medical and surgical) are described for each condition.

scholarly journals Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽  
2019 ◽  
Vol 85 (17) ◽  
pp. 1292-1303 ◽  
Author(s):  
Isabel Martínez-Solís ◽  
Nuria Acero ◽  
Francisco Bosch-Morell ◽  
Encarna Castillo ◽  
María Eugenia González-Rosende ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

scholarly journals The association between the maternal diet and the maternal and infant gut microbiome: a systematic review

2020 ◽  
pp. 1-29 ◽  
Author(s):  
Siofra E. Maher ◽  
Eileen C. O’Brien ◽  
Rebecca L. Moore ◽  
David F. Byrne ◽  
Aisling A. Geraghty ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Maternal Diet ◽  
Rrna Gene ◽  
High Fat ◽  
High Fat Diets ◽  
Culture Independent ◽  
Infant Gut Microbiome ◽  
Fat Diets

Abstract During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.

scholarly journals Transcriptome-Wide Analysis of CXCR5 Deficient Retinal Pigment Epithelial (RPE) Cells Reveals Molecular Signatures of RPE Homeostasis

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 147 ◽  
Author(s):  
Madhu Sudhana Saddala ◽  
Anton Lennikov ◽  
Anthony Mukwaya ◽  
Hu Huang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Enrichment Analysis ◽  
Age Related Macular Degeneration ◽  
Pathway Enrichment Analysis ◽  
Molecular Signatures ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in the elderly population. In our previous studies, we found that deficiency of CXCR5 causes AMD-like pathological phenotypes in mice, characterized by abnormalities and dysfunction of the retinal pigment epithelium (RPE) cells. The abnormalities included abnormal cellular shape and impaired barrier function. In the present study, primary RPE cells were derived separately from CXCR5 knockout (KO) mice and from C57BL6 wild type (WT). The isolated primary cells were cultured for several days, and then total RNA was isolated and used for library preparation, sequencing, and the resultant raw data analyzed. Relative to the WT, a total of 1392 differentially expressed genes (DEG) were identified. Gene ontology analysis showed various biological processes, cellular components, and molecular functions were enriched. Pathway enrichment analysis revealed several pathways, including the PI3K-Akt signaling, mTOR signaling, FoxO, focal adhesion, endocytosis, ubiquitin-mediated proteolysis, TNFα-NF-kB Signaling, adipogenesis genes, p53 signaling, Ras, autophagy, epithelial–mesenchymal transition (EMT), and mitochondrial pathway. This study explores molecular signatures associated with deficiency of CXCR5 in RPE cells. Many of these signatures are important for homeostasis of this tissue. The identified pathways and genes require further evaluation to better understand the pathophysiology of AMD.

The Blood–Retinal Barrier in Retinal Disease

2009 ◽  
Vol 03 (02) ◽  
pp. 105 ◽  
Author(s):  
José Cunha-Vaz ◽  
Keyword(s):  
Diabetic Retinopathy ◽  
Tight Junctions ◽  
Retinal Pigment ◽  
Water Flux ◽  
Retinal Disease ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Blood Retinal Barrier ◽  
Age Related

The blood–ocular barrier system is formed by two main barriers: the blood–aqueous barrier and the blood–retinal barrier (BRB). The BRB is particularly tight and restrictive and is a physiological barrier that regulates ion, protein and water flux into and out of the retina. The BRB consists of inner and outer components, the inner BRB being formed of tight junctions between retinal capillary endothelial cells and the outer BRB of tight junctions between retinal pigment epithelial cells. The BRB is essential to maintaining the eye as a privileged site and is essential for normal visual function. Alterations of the BRB play a crucial role in the development of retinal diseases. The two most frequent and relevant retinal diseases, diabetic retinopathy and age-related macular degeneration (AMD), are directly associated with alterations of the BRB. Diabetic retinopathy is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration of the outer BRB. Treatment of retinal diseases must also deal with the BRB either by using its specific transport mechanisms or by circumventing it through intravitreal injections

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