Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO(2)(*)-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO(*)-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies.

The common marmoset has attracted increasing interest as a model for visual neuroscience. A measurement of fundamental importance to ensure the validity of visual studies is spatial acuity. The marmoset has excellent acuity that has been reported at the fovea to be nearly half that of the human (Ordy and Samorajski []: Vision Res 8:1205-1225), a value that is consistent with them having similar photoreceptor densities combined with their smaller eye size (Troilo et al. []: Vision Res 33:1301-1310). Of interest, the marmoset exhibits a higher proportion of cones than rods in peripheral vision than human or macaque, which in principle could endow them with better peripheral acuity depending on how those signals are pooled in subsequent processing. Here, we introduce a simple behavioral paradigm to measure acuity and then test how acuity in the marmoset scales with eccentricity. We trained subjects to fixate a central point and detect a peripheral Gabor by making a saccade to its location. First, we found that accurate assessment of acuity required correction for myopia in all adult subjects. This is an important point because marmosets raised in laboratory conditions often have mild to severe myopia (Graham and Judge []: Vision Res 39:177-187), a finding that we confirm, and that would limit their utility for studies of vision if uncorrected. With corrected vision, we found that their acuity scales with eccentricity similar to that of humans and macaques, having roughly half the value of the human and with no clear departure for higher acuity in the periphery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 300-313, 2017.

Purpose To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). Design Retrospective, international, multisite study. Participants Pediatric patients (2–18 years of age at diagnosis) with IIH. Main Outcome Measures Body mass index (BMI), height, and weight Z-scores; sexual maturation. Methods Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuroophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. Results Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson’s correlation coefficient, 0.50; 95% confidence interval [CI], 0.30–0.66; P < 0.001; n = 72), and in girls, a weak association was noted (Pearson’s correlation coefficient, 0.34; 95% CI, 0.20–0.47; P < 0.001; n = 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (n = 57/233). Prepubertal participants (n = 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (n = 45; 1.92±0.60), but this result did not reach statistical significance (P = 0.09). Conclusions With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight or obese, and a late adolescent group that is mostly obese. Data also suggest that the early adolescent group with IIH may be taller than age- and gender-matched reference values. Understanding these features of pediatric IIH may help to illuminate the complex pathogenesis of this condition.

Background: Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO. Methods: We performed a retrospective, observational cohort study using data from the Optum deidentified electronic health record of 30.8 million people cross-referenced with the Medtronic CareLink database of 2.7 million people with cardiac monitoring devices in situ. We enrolled patients in 3 groups: (1) CRAO, (2) cerebral ischemic stroke, and (3) age-, sex-, and comorbidity-matched controls. The primary end point was the detection of new AF (defined as ≥2 minutes of AF detected on a cardiac monitoring device). Results: We reviewed 884 431 patient records in common between the two databases to identify 100 patients with CRAO, 6559 with ischemic stroke, and 1000 matched controls. After CRAO, the cumulative incidence of new AF at 2 years was 49.6% (95% CI, 37.4%–61.7%). Patients with CRAO had a higher rate of AF than controls (hazard ratio, 1.64 [95% CI, 1.17–2.31]) and a comparable rate to patients with stroke (hazard ratio, 1.01 [95% CI, 0.75–1.36]). CRAO was associated with a higher incidence of new stroke compared with matched controls (hazard ratio, 2.85 [95% CI, 1.29–6.29]). Conclusions: The rate of AF detection after CRAO is higher than that seen in age-, sex-, and comorbidity-matched controls and comparable to that seen after ischemic cerebral stroke. Paroxysmal AF should be considered as part of the differential etiology of CRAO, and those patients may benefit from long-term cardiac monitoring.

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There is growing evidence for the role of mitochondrial dysfunction in the toxic optic neuropathies. Due to the structural similarities between antibiotic targets and mitochondrial machinery, several antibiotics known to cause optic neuropathy have deleterious effects on mitochondrial function. We review the literature on the prevalence, clinical manifestations, and management of antibiotic induced toxic optic neuropathies. The effect of these antibiotics on mitochondrial function in regard to the optic nerve is discussed.

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