Age-related Macular Degeneration Research Research Articles

From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration

Background aimsHuman pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis. MethodsThis study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365. ResultsIn total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like “clinical trial,” “stem cell therapy,” “retinal organoid,” and “retinal progenitor cells” were predominant. ConclusionsResearch on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between “ipsc,” “induced pluripotent stem cell,” “cell culture,” and “human embryonic stem cell.” As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.

Analyzing shifts in age-related macular degeneration research trends since 2014: A bibliometric study with triple-map Sankey diagrams (TMSD).

Age-related macular degeneration (AMD) is the primary cause of vision impairment in older adults, especially in developed countries. While many articles on AMD exist in the literature, none specifically delve into the trends based on document categories. While bibliometric studies typically use dual-map overlays to highlight new trends, these can become congested and unclear with standard formats (e.g., in CiteSpace software). In this study, we introduce a unique triple-map Sankey diagram (TMSD) to assess the evolution of AMD research. Our objective is to understand the nuances of AMD articles and show the effectiveness of TMSD in determining whether AMD research trends have shifted over the past decade. We collected 7465 articles and review pieces related to AMD written by ophthalmologists from the Web of Science core collection, accumulating article metadata from 2014 onward. To delve into the characteristics of these AMD articles, we employed various visualization methods, with a special focus on TMSD to track research evolution. We adopted the descriptive, diagnostic, predictive, and prescriptive analytics (DDPP) model, complemented by the follower-leading clustering algorithm (FLCA) for clustering analysis. This synergistic approach proved efficient in identifying and showcasing research focal points and budding trends using network charts within the DDPP framework. Our findings indicate that: in countries, institutes, years, authors, and journals, the dominant entities were the United States, the University of Bonn in Germany, the year 2021, Dr Jae Hui Kim from South Korea, and the journal "Retina"; in accordance with the TMSD, AMD research trends have not changed significantly since 2014, as the top 4 categories for 3 citing, active, and cited articles have not changed, in sequence (Ophthalmology, Science & Technology - Other Topics, General & Internal Medicine, Pharmacology & Pharmacy). The introduced TMSD, which incorporates the FLCA algorithm and features in 3 columns-cited, active, and citing research categories-offers readers clearer insights into research developments compared to the traditional dual-map overlays from CiteSpace software. Such tools are especially valuable for streamlining the visualization of the intricate data often seen in bibliometric studies.

An overview of retinal light damage models for preclinical studies on age-related macular degeneration: identifying molecular hallmarks and therapeutic targets.

Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models.

Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.

Neuroprotection for Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed "exudative" or "neovascular AMD," or retinal pigment epithelium (RPE) cell and photoreceptor death, termed "geographic atrophy" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.

The relationship between citation-based metrics and Twitter in the area of age related macular degeneration research: Altmetric and bibliometric study

<b>Purpose:</b> The aim of this research is to analyze the bibliometric and altmetric scores of highly cited articles in the area of age related macular degeneration (AMD) research and to assess the correlations between them.<br /> <b>Material and methods:<i> </i></b>The data of publications in last decade were retrieved from the Web of Science Core Collection database using "age related macular degeneration" as a search term. The top 100 cited articles (T100)  list was analyzed by author name, publication year, main topic, study type, journal name, journal impact factor (IF), H-index, total citation number (TCN), average citation per year (ACpY), Altmetric attention score (AAS), and number of tweets (NTs). VOSviewer software was utilized for  visualization of  bibliometric data.<br /> <b>Results:<i> </i></b>We discovered 16.984 articles in the last decade. The median values for TCN and AAS were 221 (IQR 178–380.75) and 13 (IQR 4-37.75), respectively in T100 list. The majority of the highly cited articles in AMD research have mainly focused on AMD treatment (n=34), especially anti-vascular endothelial growth factor therapy. However, social attention was primarily on the stem cell therapy. While AAS and NTs did not have significant correlation with TCN, they did show a significant positive correlation with ACpY. AAS and NTs showed significant positive correlation with journal IF and H-index.<br /> <b>Conclusion:<i> </i></b>Treatment for AMD is the most interested issue in the area. Stem cell therapies are popular on social media. The interest of social media is on articles that continue to be cited over the years rather than articles with high total citations.

Sex Differences in RANTES (CCL5) in Patients With Intermediate Age-Related Macular Degeneration (AMD) and Controls With no AMD.

PurposeTo determine if there are sex differences in levels of regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with intermediate age-related macular degeneration (iAMD) and in controls with no AMD.MethodsPatients with iAMD and controls defined by multi-modal imaging were recruited into a Colorado AMD registry. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction.ResultsThe plasma level of RANTES was significantly higher in the control group in comparison with the iAMD group. When moderated by sex, RANTES was significantly lower (P = 0.005) in males (median, 4525.6 pg/mL; interquartile range, 2589–7861 pg/mL) compared with females (median, 6686 pg/mL; interquartile range, 3485–12488 pg/mL) within the iAMD cohort. No significant difference was found in levels of RANTES between males and females in the control group.ConclusionsWe found that levels of RANTES were moderated by sex in cases with iAMD with lower levels in males compared with females. The findings illustrate the importance of including sex as a biological variable in AMD research. There is a need for further studies of RANTES, stratified by sex, in the advanced phenotypes of AMD.Translational RelevanceThe biomarker RANTES identified in the plasma of patients with iAMD reflects systemic alterations when stratified by sex.

Progression of Age-Related Macular Degeneration Among Individuals Homozygous for Risk Alleles on Chromosome 1 (CFH-CFHR5) or Chromosome 10 (ARMS2/HTRA1) or Both

Age-related macular degeneration (AMD) is a common cause of irreversible vision loss among individuals older than 50 years. Although considerable advances have been made in our understanding of AMD genetics, the differential effects of major associated loci on disease manifestation and progression may not be well characterized. To elucidate the specific associations of the 2 most common genetic risk loci for AMD, the CFH-CFHR5 locus on chromosome 1q32 (Chr1) and the ARMS2/HTRA1 locus on chromosome 10q26 (Chr10)-independent of one another and in combination-with time to conversion to late-stage disease and to visual acuity loss. This case series study included 502 individuals who were homozygous for risk variants at both Chr1 and Chr10 (termed Chr1&10-risk) or at either Chr1 (Chr1-risk) or Chr10 (Chr10-risk) and who had enrolled in Genetic and Molecular Studies of Eye Diseases at the Sharon Eccles Steele Center for Translational Medicine between September 2009 and March 2020. Multimodal imaging data were reviewed for AMD staging, including grading of incomplete and complete retinal pigment epithelium and outer retinal atrophy. Hazard ratios and survival times for conversion to any late-stage AMD, atrophic or neovascular, and associated vision loss of 2 or more lines. In total, 317 participants in the Chr1-risk group (median [IQR] age at first visit, 75.6 [69.5-81.7] years; 193 women [60.9%]), 93 participants in the Chr10-risk group (median [IQR] age at first visit, 77.5 [72.2-84.2] years; 62 women [66.7%]), and 92 participants in the Chr1&10-risk group (median [IQR] age at first visit, 71.7 [68.0-76.3] years; 62 women [67.4%]) were included in the analyses. After adjusting for age and AMD grade at first visit, compared with 257 participants in the Chr1-risk group, 56 participants in the Chr1&10-risk group (factor of 3.3 [95% CI, 1.6-6.8]; P < .001) and 58 participants in the Chr10-risk group (factor of 2.6 [95% CI, 1.3-5.2]; P = .007) were more likely to convert to a late-stage phenotype during follow-up. This difference was mostly associated with conversion to macular neovascularization, which occurred earlier in participants with Chr1&10-risk and Chr10-risk. Eyes in the Chr1&10-risk group (median [IQR] survival, 5.7 [2.1-11.1] years) were 2.1 (95% CI, 1.1-3.9; P = .03) times as likely and eyes in the Chr10-risk group (median [IQR] survival, 6.3 [2.7-11.3] years) were 1.8 (95% CI, 1.0-3.1; P = .05) times as likely to experience a visual acuity loss of 2 or more lines compared with eyes of the Chr1-risk group (median [IQR] survival, 9.4 [4.1-* (asterisk indicates event rate did not reach 75%)] years). These findings suggest differential associations of the 2 major AMD-related risk loci with structural and functional disease progression and suggest distinct underlying biological mechanisms associated with these 2 loci. These genotype-phenotype associations may warrant consideration when designing and interpreting AMD research studies and clinical trials.

A Novel Method of Mouse RPE Explant Culture and Effective Introduction of Transgenes Using Adenoviral Transduction for In Vitro Studies in AMD.

Degeneration of retinal pigment epithelium (RPE) is one of the most critical phenotypic changes of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. While cultured polarized RPE cells with original properties are valuable in in vitro models to study RPE biology and the consequences of genetic and/or pharmacological manipulations, the procedure to establish mouse primary PRE cell culture or pluripotent stem cell-derived RPE cells is time-consuming and yields a limited number of cells. Thus, establishing a mouse in situ RPE culture system is highly desirable. Here we describe a novel and efficient method for RPE explant culture that allows for obtaining biologically relevant RPE cells in situ. These RPE explants (herein referred to as RPE flatmounts) are viable in culture for at least 7 days, can be efficiently transduced with adenoviral constructs, and/or treated with a variety of drugs/chemicals followed by downstream analysis of the signaling pathways/biological processes of interest, such as assessment of the autophagy flux, inflammatory response, and receptor tyrosine kinases stimulation. This method of RPE explant culture is highly beneficial for pharmacological and mechanistic studies in the field of RPE biology and AMD research.

Complement Factor H Loss in RPE Cells Causes Retinal Degeneration in a Human RPE-Porcine Retinal Explant Co-Culture Model.

Age-related Macular degeneration (AMD) is a degenerative disease of the macula affecting the elderly population. Treatment options are limited, partly due to the lack of understanding of AMD pathology and the lack of suitable research models that replicate the complexity of the human macula and the intricate interplay of the genetic, aging and lifestyle risk factors contributing to AMD. One of the main genetic risks associated with AMD is located on the Complement Factor H (CFH) gene, leading to an amino acid substitution in the Factor H (FH) protein (Y402H). However, the mechanism of how this FH variant promotes the onset of AMD remains unclear. Previously, we have shown that FH deprivation in RPE cells, via CFH silencing, leads to increased inflammation, metabolic impairment and vulnerability toward oxidative stress. In this study, we established a novel co-culture model comprising CFH silenced RPE cells and porcine retinal explants derived from the visual streak of porcine eyes, which closely resemble the human macula. We show that retinae exposed to FH-deprived RPE cells show signs of retinal degeneration, with rod cells being the first cells to undergo degeneration. Moreover, via Raman analyses, we observed changes involving the mitochondria and lipid composition of the co-cultured retinae upon FH loss. Interestingly, the detrimental effects of FH loss in RPE cells on the neuroretina were independent of glial cell activation and external complement sources. Moreover, we show that the co-culture model is also suitable for human retinal explants, and we observed a similar trend when RPE cells deprived of FH were co-cultured with human retinal explants from a single donor eye. Our findings highlight the importance of RPE-derived FH for retinal homeostasis and provide a valuable model for AMD research.

Nanotechnology: revolutionizing the delivery of drugs to treat age-related macular degeneration

ABSTRACT Introduction: Age-related macular degeneration (AMD) is a progressive retinal disease that degrades the eye’s ability to grasp visual acuity. The antivascular endothelial growth factor (VEGF) therapies have made significant strides in improving the quality of life, and there is a continued opportunity to improve delivery, outcomes, and patient convenience and compliance. The treatments available could gain better clinical outcome from novel therapeutics through nanotechnology application. Areas covered: This review summarizes AMD biology and the pathophysiology of the disease along with the successes and limitations of available therapies. It further discusses the promising nanotechnology modalities that could become the cornerstone of future AMD research for improving delivery and reducing frequency of administration thus, enabling development of novel therapeutics. Expert opinion: The robust translation from preclinical work to clinical outcome for AMD remains an unmet need. Continuing to investigate in deeper understanding of biology and advancing high-quality targets into the clinic in combination with the application of advanced nanotechnology to design patient-centric offerings for both dry and wet AMD is needed. Because of the lack of regulatory precedence, and challenging manufacturing and supply chain need, the future of nano-enabled technologies is challenging but presents exciting treatment options for AMD.

Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning

PurposeTo apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research.DesignRetrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.ParticipantsA total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017.MethodsA deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes.Main Outcome MeasuresVolumes of segmented features (mm3) and central subfield thickness (CST) (μm).ResultsIn first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA.ConclusionsWe report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure–function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

NEI-Supported Age-Related Macular Degeneration Research: Past, Present, and Future.

PurposeTo review past and current National Eye Institute (NEI)–supported age-related macular degeneration (AMD) activities and initiatives and preview upcoming coordinated efforts for studying AMD.MethodsWe conducted and summarized a portfolio analysis and literature review of NEI intramural and extramural AMD activities.ResultsThe NEI supports a broad range of AMD research, both by individual independent investigators as well as through networks and consortia. The International AMD Genomics Consortium, Age-Related Eye Disease Study, Age-Related Eye Disease Study 2 (AREDS2), and Comparison of AMD Treatments Trial legacy work probed the complex genetics, clinical presentation, and standards of patient care, respectively. The NEI AMD Pathobiology Working Group identified gaps and opportunities for future research efforts. The AMD Ryan Initiative Study and clinical trials testing the efficacies of minocycline to modulate retinal microglia activity and induced pluripotent stem cells–derived retinal pigmented epithelium (RPE) patch implants to rescue photoreceptor cell death are among the future directions for NEI-supported AMD research. Finally, NEI commissioned the creation of AREDS2 participant-derived induced pluripotent stem cell (iPSC) lines linked to their associated genomic and phenotypic datasets. These datasets will also be linked to the data obtained using their associated iPSC-derived cells (RPE, retina, choroid) and made publicly available.ConclusionsInvestments by NEI for AMD research will continue to provide invaluable resources to investigators committed to addressing this complex blinding disease and other retinal degenerative diseases.Translational RelevanceNEI now stands poised to expand the resources available to clinical investigators to uncover disease mechanisms and move experimental therapies into clinical trials.

Developing Therapies for Age-related Macular Degeneration: The Art and Science of Problem-solving: The 2018 Charles L. Schepens, MD, Lecture

To review the roles of analytic and innovative thought in advancing knowledge, using past examples in ophthalmology, and to explore potential strategies to improve our understanding of age-related macular degeneration (AMD) and develop new therapies. Presented as the 2018 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on October 26,2018. None. Review of published literature and sources on creativity and innovation. Recommendations for future AMD research. Innovative solutions to problems often seem intuitively obvious in hindsight. Yet, some problems seem impossible to solve. In the 1990s, AMD was a significant unmet need, with only destructive therapies for neovascular disease. This changed with the development of 2 therapies: (1) verteporfin photodynamic therapy (PDT) and (2) anti-vascular endothelial growth factor (VEGF) therapies, which are now administered to millions of people annually around the world. Now, we are frustrated by the lack of therapies for early and intermediate AMD and geographic atrophy. Photodynamic therapy and anti-VEGF drug development occurred through a combination of analytic thought and creative disruption through innovation. To get past our current impasse in understanding and treating AMD, we need to harness both analysis and innovation. We have many important building blocks in place-information on genetics, clinical findings, imaging, and histology-and have identified key pathways and potential therapeutic targets. Perhaps we need additional investigation, analysis, and integration to improve our understanding through work on structure/function and genotype/phenotype correlations and development of imaging and systemic biomarkers. We likely also need an innovative disruption. This innovation might be the concept that there are subtypes of early and intermediate AMD characterized by specific clinical phenotypes, genotype, functional characteristics, and biomarkers that are dependent on particular pathways and treatable with a specific agent. We need to encourage innovation in each of us within our research and clinical community. Although we have accumulated extensive knowledge about AMD, we are currently at an impasse in the development of new treatments. We need to continue the analytic process, but at the same time encourage innovative disruption to develop successful AMD therapies.

One- and two-year visual outcomes from the Moorfields age-related macular degeneration database: a retrospective cohort study and an open science resource

ObjectivesTo analyse treatment outcomes and share clinical data from a large, single-centre, well-curated database (8174 eyes/6664 patients with 120 756 single entries) of patients with neovascular age-related macular degeneration (AMD)...

Significant Association Between Variant in SGCD and Age-Related Macular Degeneration.

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes—for instance, in the dystrophin-associated protein complex—might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4–5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06–3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03–3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02–0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.

Omics Biomarkers in Ophthalmology.

"Omics" refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes. We observe that genomic analyses were mainly successful in AMD research (almost half of the genomic heritability has been explained), whereas large parts of disease variability or risk remain unsolved in most of the other diseases. Other omics studies like transcriptomics, proteomics, and metabolomics provided additional candidate proteins and pathways for several eye diseases, although sample sizes in these studies were often very small and replication is lacking. In order to translate omics results into clinical biomarkers, larger sample sizes and validation across different cohorts would be essential. In conclusion, omics-based studies are increasing in ophthalmology, and further application to the clinic might develop in the years to come. Integration of genomics with other type of omics data has the potential to improve the accuracy of predictive tests. Moreover, in the future, omics may lead to stratification of patients into subgroups based on molecular profiles, enabling the development of personalized treatments.

The NLRP3 Inflammasome and its Role in Age-Related Macular Degeneration.

Age related macular degeneration (AMD) is the most common cause of blindness among people of 65 years and older in developed countries (Klein and Klein, Invest Ophthalmol Vis Sci 54:7395-7401, 2013). Recent advances in dry AMD research points towards an important role of the inflammatory response in the development of the disease. The presence of inflammatory cells, antibodies, complement factors and pro-inflammatory cytokines in AMD retinas and drusen indicates that the immune system could be an important driving force in dry AMD. The NLRP3 inflammasome has been proposed as an integrator of process associated with AMD and the induction of inflammation. Herein we summarize the most recent studies that attempt to understand the role of the NLRP3 inflammasome in AMD.

Tapping Stem Cells to Target AMD: Challenges and Prospects.

Human pluripotent stem cells (hPSCs) are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD), the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs), in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

Differential Gene Expression in Age-Related Macular Degeneration.

Gene expression is the first step in ascribing function between an associated gene and disease. Understanding how variation in a gene influences expression, particularly in tissues affected by the disease, may help elucidate what influences the phenotypic outcome of that disease. Previous studies of the genetics of age-related macular degeneration (AMD) have identified several risk factors, but have not yet bridged the gap between gene association and identifying a specific mechanism or function that is involved in the pathogenesis of AMD. Advances in genomic technologies, such as RNA sequencing (RNA-seq), single cell RNA-seq, bilsulfite sequencing, and/or whole genome methylation, will be powerful tools for identifying genes/pathways that are differentially expressed in those with AMD versus those without AMD. These technologies should advance the field of AMD research so that appropriate preventive and therapeutic targets can be developed.