Wound Modulations in Glaucoma Surgery: A Systematic Review.

Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control.

Leg and arm adiposity is inversely associated with diastolic hypertension in young and middle-aged United States adults.

BACKGROUND: We sought to determine the association between appendicular adiposity and hypertension, with the purpose of better understanding the role of body fat distribution on blood pressure (BP). METHODS: We included 7411 adults aged 20 to 59 who were not taking antihypertensives and without cardiovascular disease from the 2011 to 2018 National Health and Nutrition Examination Surveys. Leg & arm adiposity, determined via dual-energy X-ray absorptiometry scans, was defined as percent of total body fat present in legs/arms (leg/total%, arm/total%). Measures were categorized into sex-specific tertiles. We estimated change in BP and odds ratios (ORs) of hypertension (BP ≥ 130/80) and hypertension subtypes using multivariable, survey design-adjusted linear & logistic regression, respectively. RESULTS: Of the participants, 49% were female, the average (standard deviation) age was 37.4 (0.3) years, and 24% had hypertension. Those in the highest tertile (T3) of leg/total% had 30% decreased adjusted ORs (aOR) of hypertension compared to the lowest tertile (T1; aOR, 0.70; 95% confidence interval [95% CI], 0.55-0.89). This association was not significant for arm/total% (0.89, 0.68-1.17). T3 of leg/total% was associated with 49% lower, 41% lower, and unchanged relative odds of isolated diastolic hypertension (IDH), systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH) compared to T1 (IDH: 0.51, 0.37-0.70; SDH: 0.59, 0.43-0.80; ISH: 1.06, 0.70-1.59). For every 10% increase in leg/total%, diastolic BP decreased by an adjusted mean 3.5 mmHg (95% CI, - 4.8 to - 2.2) in males and 1.8 mmHg (95% CI, - 2.8 to - 0.8) in females (P < 0.001 for both). CONCLUSIONS: A greater proportional distribution of fat around the legs is inversely, independently associated with hypertension, and more specifically, diastolic hypertension (IDH and SDH).

Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner.

Maternal methyl donor supplementation during pregnancy has demonstrated lasting influence on offspring DNA methylation. However, it is unknown whether an adverse postnatal environment, such as high-fat (HF) feeding, overrides the influence of prenatal methyl donor supplementation on offspring epigenome. In this study, we examined whether maternal supplementation of choline (CS), a methyl donor, interacts with prenatal and postnatal HF feeding to alter global and site-specific DNA methylation in offspring. We fed wild-type C57BL/6J mouse dams a HF diet with or without CS throughout gestation. After weaning, the offspring were exposed to HF feeding for 6 weeks resembling a continued obesogenic environment. Our results suggest that maternal CS under the HF condition (HFCS) increased global DNA methylation and DNA methyltransferase 1 (Dnmt1) expression in both fetal liver and brain. However, during the postnatal period, HFCS offspring demonstrated lower global DNA methylation and Dnmt1 expression was unaltered in both the liver and visceral adipose tissue. Site-specific DNA methylation analysis during both fetal and postnatal periods demonstrated that HFCS offspring had higher methylation of CpGs in the promoter of Srebf1, a key mediator of de novo lipogenesis. In conclusion, the influence of maternal CS on offspring DNA methylation is specific to HF feeding status during prenatal and postnatal periods. Without continued CS during the postnatal period, global DNA methylation enhanced by prenatal CS in the offspring was overridden by postnatal HF feeding.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring.

Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic responses. In male offspring, while post-weaning HF led to impaired fasting glucose and worse glucose tolerance (p < 0.05), MCS in HF dams (HFCS) attenuated these changes. HFCS (versus maternal normal fat control) appeared to improve metabolic functioning of visceral adipose tissue during post-weaning HF feeding, preventing the elevation in leptin and increasing (p < 0.05) mRNA expression of insulin receptor substrate 1 (Irs1) that promotes peripheral insulin signaling in male offspring. In contrast, MCS had minimal effects on metabolic outcomes of female offspring. In conclusion, MCS during HF feeding in mice improves long-term blood glucose homeostasis in male offspring when they are faced with a postnatal obesogenic environment.