Analysing Retinal Disease Using Cleha and Thresholding

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

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Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes

Scientific Reports ◽

10.1038/s41598-021-83552-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Jin Kim ◽

◽

Kemal Sonmez ◽

Ryan Swan ◽

J. Peter Campbell ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Preterm Infants ◽

Premature Infants ◽

Retinopathy Of Prematurity ◽

Smooth Endoplasmic Reticulum ◽

Enrichment Analysis ◽

Retinal Disease ◽

Gene Set Enrichment Analysis ◽

Whole Exome

AbstractRetinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.

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Retinitis pigmentosa is associated with shifts in the gut microbiome

Scientific Reports ◽

10.1038/s41598-021-86052-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Oksana Kutsyr ◽

Lucía Maestre-Carballa ◽

Mónica Lluesma-Gomez ◽

Manuel Martinez-Garcia ◽

Nicolás Cuenca ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Gut Microbiome ◽

Functional Decline ◽

Retinal Disease ◽

Photoreceptor Cells ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Sequencing Data ◽

Alpha And Beta Diversity ◽

Potential Biomarker

AbstractThe gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice. In rd10 mice, retinal responsiveness to flashlight stimuli and visual acuity were deteriorated with respect to observed in age-matched control mice. This functional decline in dystrophic animals was accompanied by photoreceptor loss, morphologic anomalies in photoreceptor cells and retinal reactive gliosis. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. Remarkably, four fairly common ASV in healthy gut microbiome belonging to Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp. were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with RP. The results indicate that retinal degenerative changes in RP are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.

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Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant

Scientific Reports ◽

10.1038/s41598-020-80400-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ine Strubbe ◽

Caroline Van Cauwenbergh ◽

Julie De Zaeytijd ◽

Sarah De Jaegere ◽

Marieke De Bruyne ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Somatic Mosaicism ◽

Retinal Disease ◽

Hair Follicles ◽

Disease Genes ◽

Female Carrier ◽

Autofluorescence Imaging ◽

Targeted Next Generation Sequencing ◽

Whole Exome ◽

Next Generation Sequencing Ngs

AbstractWe describe both phenotype and pathogenesis in two male siblings with typical retinitis pigmentosa (RP) and the potentially X-linked RP (XLRP) carrier phenotype in their mother. Two affected sons, two unaffected daughters, and their mother underwent detailed ophthalmological assessments including Goldmann perimetry, color vision testing, multimodal imaging and ISCEV-standard electroretinography. Genetic testing consisted of targeted next-generation sequencing (NGS) of known XLRP genes and whole exome sequencing (WES) of known inherited retinal disease genes (RetNet-WES). Variant validation and segregation analysis were performed by Sanger sequencing. The mutational load of the RHO variant in the mother was assessed in DNA from leucocytes, buccal cells and hair follicles using targeted NGS. Both affected sons showed signs of classical RP, while the mother displayed patches of hyperautofluorescence on blue light autofluorescence imaging and regional, intraretinal, spicular pigmentation, reminiscent of a carrier phenotype of XLRP. XLRP testing was negative. RetNet-WES testing revealed RHO variant c.404G > C p.(Arg135Pro) in a mosaic state (21% of the reads) in the mother and in a heterozygous state in both sons. Targeted NGQSS of the RHO variant in different maternal tissues showed a mutation load between 25.06% and 41.72%. We report for the first time that somatic mosaicism of RHO variant c.404G > C p.(Arg135Pro) mimics the phenotype of a female carrier of XLRP, in combination with heterozygosity for the variant in the two affected sons.

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Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease

Journal of Clinical Medicine ◽

10.3390/jcm10061254 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1254

Author(s):

Warren W. Pan ◽

Thomas W. Gardner ◽

Jennifer L. Harder

Keyword(s):

Systems Biology ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Vision Loss ◽

Retinal Disease ◽

Diabetic Kidney ◽

New Therapies ◽

Traditional Research ◽

Working Age ◽

Culture Models

Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models—a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual’s specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.

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

Journal of Personalized Medicine ◽

10.3390/jpm11050321 ◽

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.

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

Ophthalmologica ◽

10.1159/000515148 ◽

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.

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