Bile acids (BAs) are amphipathic sterols primarily synthesized from cholesterol in the liver and released in the intestinal lumen upon food intake. BAs play important roles in micellination of dietary lipids, stimulating bile flow, promoting biliary phospholipid secretion, and regulating cholesterol synthesis and elimination. Emerging evidence, however, suggests that, aside from their conventional biological function, BAs are also important signaling molecules and therapeutic tools. In the last decade, the therapeutic applications of BAs in the treatment of ocular diseases have gained great interest. Despite the identification of BA synthesis, metabolism, and recycling in ocular tissues, much remains unknown with regards to their biological significance in the eye. Additionally, as gut microbiota directly affects the quality of circulating BAs, their analysis could derive important information on changes occurring in this microenvironment. This review aims at providing an overview of BA metabolism and biological function with a focus on their potential therapeutic and diagnostic use for retinal diseases.
PurposeLimited research exists on the time course of long-term retinal and cerebral deficits in diabetic rodents. Previously, we examined short term (4–8 weeks) deficits in the Goto-Kakizaki (GK) rat model of Type II diabetes. Here, we investigated the long-term (1–8 months) temporal appearance of functional deficits (retinal, cognitive, and motor), retinal vascular pathology, and retinal dopamine levels in the GK rat.MethodsIn GK rats and Wistar controls, retinal neuronal function (electroretinogram), cognitive function (Y-maze), and motor function (rotarod) were measured at 1, 2, 4, 6, and 8 months of age. In addition, we evaluated retinal vascular function (functional hyperemia) and glucose and insulin tolerance. Retinas from rats euthanized at ≥8 months were assessed for vascular pathology. Dopamine and DOPAC levels were measured via HPLC in retinas from rats euthanized at 1, 2, 8, and 12 months.ResultsGoto-Kakizaki rats exhibited significant glucose intolerance beginning at 4 weeks and worsening over time (p < 0.001). GK rats also showed significant delays in flicker and oscillatory potential implicit times (p < 0.05 to p < 0.001) beginning at 1 month. Cognitive deficits were observed beginning at 6 months (p < 0.05), but no motor deficits. GK rats showed no deficits in functional hyperemia and no increase in acellular retinal capillaries. Dopamine levels were twice as high in GK vs. Wistar retinas at 1, 2, 8, and 12 months (p < 0.001).ConclusionAs shown previously, retinal deficits were detectable prior to cognitive deficits in GK rats. While retinal neuronal function was compromised, retinal vascular pathology was not observed, even at 12+ months. High endogenous levels of dopamine in the GK rat may be acting as an anti-angiogenic and providing protection against vascular pathology.
Since late 2019, SARS-CoV-2 has differentially impacted geographies and population demographics as it spread. As of June 30, 2020, two hotspots within the United States of America—the states of Georgia and Michigan—exhibited similar numbers of cases while Michigan had over twice the case fatality rate (CFR) of Georgia. Given the similar populations, land areas, and pandemic timelines of these states, such a large difference is unexpected. The primary goal of this paper is to examine why Michigan experienced much higher COVID-19 mortality than Georgia, which may point to at-risk comorbidities and vulnerable populations. We examined publicly available data on demographics, rates of comorbidities, environmental factors, and other population differences at the state and local levels (the cities of Detroit, Michigan; Atlanta, Georgia; and Albany, Georgia) that have known or identified associations with health outcomes. We also outlined the timeline of the pandemic in each state to determine if the actions of state governments may have contributed to the observed difference in CFR. While the difference in state CFR may imply that Michigan handled the pandemic poorly, the data show that inherent characteristics of Detroit may have led to the higher statewide CFR. Notable differences between the states include elderly populations, agricultural statistics, and drinking habits. Notable differences between the cities included population density, health system quality, per capita income, race, education, media access, and air pollution. Hypertension (among blacks), diabetes (at the city level), chronic kidney disease, asthma, heart disease, and cancer differed in prevalence by location and were associated with increased severity and/or mortality of COVID-19. There were more deaths due to COVID-19 in African American communities and nursing homes in Michigan. A combination of these factors likely explains the differential impact between these two states.
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