Consilience and unity in ocular anterior segment research.

In his beautiful book, , the eminent biologist Edward O Wilson, advocates the need for integration and reconciliation across the sciences. He defines consilience as "literally a 'jumping together' of knowledge with a linking of facts ..

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation (DNAm) provides a crucial epigenetic mark linking genetic variations to environmental influence. We analyzed array-based DNAm profiles of 160 human retinas with co-measured RNA-seq and > 8 million genetic variants, uncovering sites of genetic regulation in (37,453 mQTLs and 12,505 eQTLs) and 13,747 eQTMs (DNAm loci affecting gene expression), with over one-third specific to the retina. mQTLs and eQTMs show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism.

Astrocytoma and glioblastoma IDH1-wildtype cells colonize tumor vessels and deploy vascular mimicry.

Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular aspects have been published; however, these were not complemented with ultrastructural evidence. Our ultrastructural examination of glioma vessels reveals several unique and critical features related to their mechanisms of progression and metastasis strategy.

Comparative survey of mitochondrial ultrastructure in -mutant astrocytoma and -wildtype glioblastoma (GBM).

Gliomas are the most common malignant brain tumors with poor prognosis. The WHO's classification recognizes isocitrate dehydrogenase 1 () mutant astrocytoma and -wildtype glioblastoma (GBM). The mutation confers a survival advantage over the wildtype.

Systematic assessment of the contribution of structural variants to inherited retinal diseases.

Despite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined were subjected to WGS.

Association of Metformin With the Development of Age-Related Macular Degeneration.

Importance: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.

Objective: To investigate the association between metformin use and age-related macular degeneration (AMD).

Supporting discovery and development of medical countermeasures for chemical injury to eye and skin.

Vesicants, from vesica (Latin for blister), can cause local and systemic toxicity. They include the chemotherapy drug nitrogen mustard and chemical warfare agents sulfur mustard, Lewisite, and phosgene oxime. These agents are commonly released in vapor form and consequently, eyes and skin are the most vulnerable.

Cataract Surgery and the Risk of Developing Late Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 Report Number 27.

Purpose: To evaluate the risk of developing late age-related macular degeneration (AMD) after incident cataract surgery.

Design: A prospective cohort study within a randomized controlled clinical trial of oral supplementation for the treatment of AMD, the Age-Related Eye Disease Study 2 (AREDS2).

Participants: AREDS2 participants aged 50 to 85 years with bilateral large drusen or unilateral late AMD.

Pigment epithelium-derived factor (PEDF) and derived peptides promote survival and differentiation of photoreceptors and induce neurite-outgrowth in amacrine neurons.

Pigment epithelium-derived factor (PEDF) is a cytoprotective protein for the retina. We hypothesize that this protein acts on neuronal survival and differentiation of photoreceptor cells in culture. The purpose of the present study was to evaluate the neurotrophic effects of PEDF and its fragments in an in vitro model of cultured primary retinal neurons that die spontaneously in the absence of trophic factors.

Multiple Evanescent White Dot Syndrome Presenting After Initiation of Empagliflozin, a Sodium-Glucose Cotransporter-2 Inhibitor.

Multiple evanescent white dot syndrome (MEWDS) is an inflammatory condition of the retina that typically presents unilaterally with multiple gray-white spots in the outer retina or retinal pigmented epithelium and granular changes within the fovea. We report a case of new-onset MEWDS in a patient closely after the initiation of empagliflozin, a sodium-glucose cotransporter inhibitor medicine for his type II diabetes mellitus.

Identification of Deep-Intronic Splice Mutations in a Large Cohort of Patients With Inherited Retinal Diseases.

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions.

Ocular Surface - Merging Challenges and Opportunities.

Dichotomies are double-edged: they can simplify and enlighten as well as exaggerate and entangle. Seeing the eye as anterior segment vs. posterior segment simplifies the formidable task of dissecting the function of the eye.

Considerations in developing medical countermeasures against chemical ocular toxicity.

The Chemical Countermeasures Research Program (CCRP) was established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID/NIH) on behalf of the National Institutes of Health Office of the Director (NIH OD). It is a trans-NIH initiative to expedite the discovery and early development of medical countermeasures (MCMs) that can reduce mortality and serious morbidity during and after large consequence public health emergency involving the deliberate or accidental large-scale release of highly toxic chemicals (HTCs).

Age-related Macular Degeneration: Nutrition, Genes and Deep Learning-The LXXVI Edward Jackson Memorial Lecture.

Purpose: To evaluate the importance of nutritional supplements, dietary pattern, and genetic associations in age-related macular degeneration (AMD); and to discuss the technique of artificial intelligence/deep learning to potentially enhance research in detecting and classifying AMD.

Design: Retrospective literature review.

Methods: To review the studies of both prospective and retrospective (post hoc) analyses of nutrition, genetic variants, and deep learning in AMD in both the Age-Related Eye Disease Study (AREDS) and AREDS2.

Genotype-phenotype associations in a large PRPH2-related retinopathy cohort.

Molecular variant interpretation lacks disease gene-specific cohorts for determining variant enrichment in disease versus healthy populations. To address the molecular etiology of retinal degeneration, specifically the PRPH2-related retinopathies, we reviewed genotype and phenotype information obtained from 187 eyeGENE® participants from 161 families. Clinical details were provided by referring clinicians participating in the eyeGENE® Network.

Age-related changes of the retinal microvasculature.

Purpose: Blood vessels of the retina provide an easily-accessible, representative window into the condition of microvasculature. We investigated how retinal vessel structure captured in fundus photographs changes with age, and how this may reflect features related to patient health, including blood pressure.

Results: We used two approaches.

Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates.

Purpose: To characterize the intraocular immune response following transplantation of iPS-derived allogeneic RPE cells into the subretinal space of non-immune-suppressed rhesus macaques.

Methods: GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a two-stage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging.

Association of Mortality with Ocular Diseases and Visual Impairment in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 13.

Purpose: To evaluate the association of mortality with visual acuity (VA) impairment, age-related macular degeneration (AMD), and cataract surgery.

Design: Cohort study.

Participants: Participants with at least intermediate AMD enrolled in a randomized controlled clinical trial of lutein/zeaxanthin and/or omega-3 fatty acids, the Age-Related Eye Disease Study 2 (AREDS2), for treatment of AMD and cataract.