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Objective: Iridocorneal angle (ICA) narrowing is a known risk factor for primary glaucoma in multiple species, but has not been described in companion rabbits. This study aimed to develop an ICA grading scheme for companion rabbits to enable early glaucoma predisposition diagnosis. Animals studied: Twenty healthy rabbits of varying breeds and ages. Procedures: Rabbits received complete ophthalmic examinations, including gonioscopy, and imaging of the ICA using spectral‐domain optical coherence tomography (SD‐OCT), Scheimpflug imaging (Pentacam® HR), and high‐resolution ultrasound (HRUS). Angle opening distance (AOD) and angle recess area (ARA) of the ICA were measured and assessed for agreement using a Bland‐Altman analysis. A five‐stage gonioscopy grading scheme was created, and Spearman‐rank test assessed for correlation between gonioscopy grades and ICA measurements. Differences among age and sex were analyzed with a nonparametric ANOVA and Wilcoxon rank‐sum test, respectively. Results: Analysis revealed AOD medians of 0.28mm for SD‐OCT [95% CI: 0.24‐0.31], 0.20mm for Pentacam® HR [95% CI: 0.18‐0.21], and 0.25mm for HRUS [95% CI: 0.22‐0.28]. The median ARA was 0.14mm2 for SD‐OCT [95% CI: 0.117‐0.163], 0.09mm2 for Pentacam® HR [95% CI: 0.082‐0.100], and 0.06mm2 for HRUS [95% CI: 0.046‐0.054]. The association between gonioscopy grade and SD‐OCT ARA was significant (P < 0.05), and there was a significant difference (P < 0.001) between imaging modalities for both ARA and AOD. Conclusions: Gonioscopy grade correlated well with SD‐OCT ARA. Therefore, SD‐OCT is recommended as a noncontact method for evaluating companion rabbit ICA. Each imaging device should not be used interchangeably for ICA evaluation. [ABSTRACT FROM AUTHOR]

Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. We examined the effects of a high-fat diet (HFD) during pregnancy on fetal skeletal muscle metabolism and metabolic risk parameters using an ovine model. White-faced ewes were fed a standardized diet containing 5% fat wt/wt (CON), or the same diet supplemented with 6% rumen-protected fats (11% total fat wt/wt; HFD) beginning 2 wk before mating until midgestation (GD75). Maternal HFD increased maternal weight gain, fetal body weight, and low-density lipoprotein levels in the uterine and umbilical circulation but had no significant effects on circulating glucose, triglycerides, or placental fatty acid transporters. Fatty acid (palmitoylcarnitine) oxidation capacity of permeabilized hindlimb muscle fibers was >50% higher in fetuses from HFD pregnancies, whereas pyruvate and maximal (mixed substrate) oxidation capacities were similar to CON. This corresponded to greater triacylglycerol content and protein expression of fatty acid transport and oxidation enzymes in fetal muscle but no significant effect on respiratory chain complexes or pyruvate dehydrogenase expression. However, serine-308 phosphorylation of insulin receptor substrate-1 was greater in fetal muscle from HFD pregnancies along with c-jun-NH 2 terminal kinase activation, consistent with prenatal inhibition of skeletal muscle insulin signaling. These results indicate that maternal high-fat feeding shifts fetal skeletal muscle metabolism toward a greater capacity for fatty acid over glucose utilization and favors prenatal development of insulin resistance, which may predispose offspring to metabolic syndrome later in life. NEW & NOTEWORTHY Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. This study examined the effects of a high-fat diet during pregnancy on metabolic risk parameters using a new sheep model. Results align with findings previously reported in nonhuman primates, demonstrating changes in fetal skeletal muscle metabolism that may predispose offspring to metabolic syndrome later in life.

Mitochondria utilize the majority of oxygen (O 2 ) consumed by aerobic organisms as the final electron acceptor for oxidative phosphorylation (OXPHOS) but also to generate reactive oxygen species (mtROS) that participate in cell signaling, physiological hormesis, and disease pathogenesis. Simultaneous monitoring of mtROS production and oxygen consumption ( J o 2 ) from tissue mitochondrial preparations is an attractive investigative approach, but it introduces dynamic changes in media O 2 concentration ([O 2 ]) that can confound experimental results and interpretation. We utilized high-resolution fluorespirometry to evaluate J o 2 and hydrogen peroxide release ( J h 2 o 2 ) from isolated mitochondria (Mt), permeabilized fibers (Pf), and tissue homogenates (Hm) prepared from murine heart and skeletal muscle across a range of experimental [O 2 ]s typically encountered during respirometry protocols (400-50 µM). Results demonstrate notable variations in J h 2 o 2 across tissues and sample preparations during nonphosphorylating (LEAK) and OXPHOS-linked respiration states at 250 µM [O 2 ] but a linear decline in J h 2 o 2 of 5-15% per 50-µM decrease in chamber [O 2 ] in all samples. J o 2 was generally stable in Mt and Hm across [O 2 ]s above 50 µM but tended to decline below 250 µM in Pf, leading to wide variations in assayed rates of J h 2 o 2 /O 2 across chamber [O 2 ]s and sample preparations. Development of chemical background fluorescence from the H 2 O 2 probe (Amplex Red) was also O 2 sensitive, emphasizing relevant calibration considerations. This study highlights the importance of monitoring and reporting the chamber [O 2 ] at which J o 2 and J h 2 o 2 are recorded during fluorespirometry experiments and provides a basis for selecting sample preparations for studies addressing the role of mtROS in physiology and disease.

The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 wk ( n = 9-11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia-reperfusion protocol. Gut microbiota was characterized by 16S rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass, and myocardial infarct size, which were associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass, and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity. NEW & NOTEWORTHY These data are the first to demonstrate that cecal microbiota transplantation (CMT) can alter cardiovascular pathology in lean and obese mice independent from alterations in dietary intake. Myocardial infarct size was reduced in obese mice receiving lean CMT and worsened in lean mice receiving obese CMT. Lean mice receiving obese CMT also displayed increased aortic stiffness. These changes were accompanied by alterations in short-chain fatty acids and gut permeability.