Dose response and time course of manganeseenhanced magnetic resonance imaging for visual pathway tracing in vivo

Axonal tracing is useful for detecting optic nerve injury and regeneration,but many commonly used methods cannot be used to observe axoplasmic flow and synaptic transmission in vivo.Manganese（Mn^2＋）-enhanced magnetic resonance imaging（MEMRI） can be used for in vivo longitudinal tracing of the visual pathway.Here,we explored the dose response and time course of an intravitreal injection of Mn Cl2 for tracing the visual pathway in rabbits in vivo using MEMRI.We found that 2 m M Mn Cl2 enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus,whereas at all other doses tested（5–40 m M）,images of the visual pathway from the retina to the contralateral superior colliculus were significantly enhanced.The images were brightest at 24 hours,and then decreased in brightness until the end of the experiment（7 days）.No signal enhancement was observed in the visual cortex at any concentration of Mn Cl2.These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo.Signal enhancement in MEMRI depends on the dose of Mn Cl2,and the strongest signals appear 24 hours after intravitreal injection.

Varicella-zoster virus as a causative agent of acute retinal necrosis in younger patients

Background: Herpes virus is considered to be the pathogen of acute retinal necrosis (ARN) infection. Previous studies have that patients with ARN caused by the varicella-zoster virus (VZV) are often older, and patients with herpes simplex virus (HSV) induced ARN are considerably younger. However, in our clinical work, we find that VZV is also a pathogen in younger ARN patients. We, therefore, aimed to analyze the common etiology of younger ARN patients. Methods: A retrospective analysis was made of 20 eyes (18 patients) diagnosed as having ARN in the Department of Ophthalmology of Peking Union Medical College Hospital from 2014 to 2016. All patients were reviewed for demographic data, clinical course, clinical manifestations, time from onset to initial physician visit, duration of follow-up, visual acuity at both presentation and final visit, and treatment strategies. A paired t test was used to compare visual acuity between the presenting vision and those of final follow-up. Vitreous or aqueous specimens from 18 eyes of 18 patients were analyzed with multiplex polymerase chain reaction (mPCR)/quantitative PCR (qPCR) and xTAG-liquid chip technology (xTAG-LCT) to determine the causative virus of ARN. Results: Final best visual acuity (BCVA) improved significantly from 1.36±0.95 (median 20/400) to 0.95±0.82 (median 20/100)￠=2.714, P = 0.015) after systemic and intravitreal antiviral treatment combined with or without pars plana vitrectomy. PCR and xTAG-LCT results showed four of the five samples in the younger group (32.2±5.2 years) and 12 of the 13 samples in the senior group (53.6±4.9 years) were positive for VZV, and two of the five samples in the younger group were positive for HSV-1. Conclusions: This study demonstrates that VZV is also a common causative virus for ARN in younger patients. Considering this finding, a systemic antiviral treatment protocol should be immediately changed to intravenous ganciclovir when the patient does not respond to acyclovir before determining the causative virus, especially in younger patients.

Ability of Mn2＋ to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration

Background： Manganese-enhanced magnetic resonance imaging （MEMR1） for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2＋ to understand the applicability of MEMR1. Methods： Forty New Zealand rabbits were divided into 0.05 mool/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group （n ： 10 in each group）. Each group was i-hrther subdivided into epithelium-removed and epithelium-intact subgroups （n = 5 in each subgroup）. Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2＋ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2＋ was evaluated with corneal imaging and pathology slices. Results： Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2＋ concentration times. The intraocular Mn2＋ concentration increased with the concentration gradients ofMn2＋ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved ill the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2. were 5087 ~ 666 ng/ml, 22920 ± 1188 ng/ml ill the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions： The corneal epithelium is a barrier to Mn2＋, and the iris and lens septum might be another intraocular banier to the permeation of Mn2＋. An elevated Mn2＋ concentration contributes to the increased permeation of Mn2＋, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2＋ concentration in the vitreous body.