INTRODUCTIONBrain cell–derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment.METHODSTotal sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI‐AD; n = 6), and AD dementia (n = 11). Various brain cell–derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs.RESULTSmiRNAs in sEV subtypes differentially expressed in MCI, MCI‐AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI).DISCUSSIONmiRNA analyses in specific sEVs could serve as a novel blood‐based molecular biomarker for AD.Highlights Multiple brain cell–derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEVCD31 and sEVPDGFRβ suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.

Objective: To investigate the impact of socioeconomic disadvantage and diabetic retinopathy severity on follow-up for vision care among people with diabetes mellitus (DM) residing in rural Vermont and northern New York State. Methods: A retrospective chart review of people with DM who visited our academic eye clinic at least once between October 1, 2015, and March 31, 2016, was done. Of 1,466 unique patient visits, 500 were chosen for full chart review by simple random sampling. DM follow-up within 1 year was recommended for 331 adults. Data about prescribed and actual follow-up intervals were extracted. Regression models were used to identify factors associated with poor attendance at follow-up appointments. Results: Sixty-eight [20.5%] patients had poor follow-up, defined as no ophthalmology visit within double the prescribed interval. Of these, 57 were not seen in follow-up by the end of study observation. Poor follow-up was greatest among socioeconomically disadvantaged patients, as defined by Medicaid enrollment (odds ratio [OR], 1.95; 95% CI, 1.07-3.56) in comparison to non-disadvantaged patients. Follow-up was better among those with moderate or worse diabetic retinopathy (OR, 0.38 95% CI, 0.20-0.70), and those with macular edema (OR, 0.19; 95% CI, 0.057-0.62). Conclusion: Medicaid insurance and better diabetic retinopathy status were associated with worse follow-up among our predominantly rural population of patients. Patients who did not follow-up within double the recommended interval were unlikely to follow-up at all. Interventions are needed to target those at highest risk for poor follow-up.

Vasculogenesis and angiogenesis are physiological mechanisms occurring throughout the body. Any disruption to the precise balance of blood vessel growth necessary to support healthy tissue, and the inhibition of abnormal vessel sprouting has the potential to negatively impact stages of development and/or healing. Therefore, the identification of key regulators of these vascular processes is critical to identifying therapeutic means by which to target vascular-associated compromises and complications. Nuclear receptors are a family of transcription factors that have been shown to be involved in modulating different aspects of vascular biology in many tissues systems. Most recently, the role of nuclear receptors in ocular biology and vasculopathies has garnered interest. Herein, we review studies that have used in vitro assays and in vivo models to investigate nuclear receptor-driven pathways in two ocular vascular diseases associated with blindness, wet or exudative age-related macular degeneration, and proliferative diabetic retinopathy. The potential therapeutic targeting of nuclear receptors for ocular diseases is also discussed.

The choroid is a vulnerable tissue site in the eye, impacted in several blinding diseases including age related macular degeneration (AMD), which is the leading cause of central vision loss in the aging population. Choroidal thinning and choriocapillary dropout are features of the early form of AMD, and endothelial dysfunction and vascular changes are primary characteristics of the neovascular clinical sub-type of AMD. Given the importance, the choroidal endothelium and outer vasculature play in supporting visual function, a better understanding of baseline choroidal signaling pathways engaged in tissue and cellular homeostasis is needed. Nuclear receptors are a large family of transcription factors responsible for maintaining various cellular processes during development, aging and disease. Herein we developed a comprehensive nuclear receptor atlas of human choroidal endothelial cells and freshly isolated choroidal tissue by examining the expression levels of all members of this transcription family using quantitative real time PCR. Given the close relationship between the choroid and retinal pigment epithelium (RPE), this data was cross-referenced with the expression profile of nuclear receptors in human RPE cells, to discover potential overlap versus cell-specific nuclear receptor expression. Finally, to identify candidate receptors that may participate in the pathobiology of AMD, we cataloged nuclear receptor expression in a murine model of wet AMD, from which we discovered a subset of nuclear receptors differentially regulated following neovascularization. Overall, these databases serve as useful resources establishing the influence of nuclear receptor signaling pathways on the outer vascular tissue of the eye, while providing a list of receptors, for more focused investigations in the future, to determine their suitability as potential therapeutic targets for diseases, in which the choroid is affected.

We live in an age where new technologies, and organizations involved in the distribution of biological materials, such as cell culture lines, have eased accessibility to a variety of in vitro models, developed, and/or harvested from different sources. In translational and basic ophthalmology research, in vitro assays are an essential component to discovery and preclinical studies. It is, therefore, of utmost importance for vision researchers to be cognizant of the risks surrounding the use of newly developed cell culture models and how scientific integrity could be impacted when standard operating procedures are not followed for cell line validation and identification. Herein, we discuss authentication challenges we faced when we obtained a newly marketed human choroidal endothelial cell line for vision research, and outline our process of validating and characterizing primary human choroidal endothelial cell lines in the laboratory.