Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive pavlovian conditioning and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells. Here we used serial electron microscopy reconstructions to quantify polyribosomes in LA dendrites when consolidation was blocked by the cap-dependent initiation inhibitor 4EGI-1. We found that 4EGI-1 depleted polyribosomes in dendritic shafts and selectively prevented their upregulation in spine heads, but not bases and necks, during consolidation. Cap-independent upregulation was specific to spines with small, astrocyteassociated synapses. Our results reveal that cap-dependent initiation is involved in local translation during learning and that local translational control varies with synapse type.
Objective: To report refractive outcomes of scleral-fixated intraocular lenses (IOLs) with Gore-Tex suture and combined pars plana vitrectomy, and to compare predicted refractive outcomes between five IOL power calculation formulas. Design: Retrospective case series. Subjects: Patients undergoing scleral-fixated of intraocular lenses with Gore-Tex suture at our institution between January 2015 and June 2018. Methods: Comparison of preoperative biometrics with postoperative refraction, calculation of predicted refractive outcome with 5 different IOL formulas. Main Outcome Measures: Prediction error and absolute error to compare postoperative refraction with refraction predicted by lens power calculation formulas.Results: Thirty-one eyes of 31 patients were included. All power calculations assumed "in-thebag" position of the IOL. Akreos AO60 was implanted in 23 and CZ70BD in 8, and all lenses were sutured 3 millimeters behind the limbus. Average postoperative spherical equivalent was −0.79 ± 0.95 diopters (D). Average prediction error (postoperative spherical equivalent refraction minus target refraction) was −0.19 ± 0.72D. Postoperative spherical equivalent was within 1.0D of target in 25/31 (81%) of patients and within 2.0D of target in 31/31 (100%). The repeatedmeasures analysis of variance of absolute error by lens power formula was significant (p=0.012), with Haigis demonstrating greater error. There was no significant difference between Barrett II, SRKT, Holladay 2, or Hoffer Q.
Aqueous tear-deficient dry eye disease is a multifactorial chronic disorder, in which the lacrimal gland fails to produce enough tears to maintain a healthy ocular surface. Some severe cases may develop corneal damage and significant vision loss. Treatment primarily involves palliation using ocular surface lubricants, but can only provide temporary relief. Construction of a bioengineered lacrimal gland having functional secretory epithelial cells is a potentially promising option for providing long-term relief to severe dry eye patients. Using sphere-forming culture techniques, we cultured adult rabbit lacrimal gland progenitor cells and prepared a lacrimal gland scaffold by decellularization. When progenitor cells were seeded onto the decellularized scaffold, they formed duct- and acinar-like structures in the three-dimensional culture system. Lacrimal gland epithelial cells showed good cell viability, cell differentiation, and secretory function in decellularized lacrimal gland matrix, as indicated by morphology, immunostaining, and β-hexosaminidase secretion assay. This study demonstrated the potential suitability of utilizing tissue-specific progenitor cells and a tissue-derived bioscaffold for lacrimal gland restoration.
Traumatic epidural hematomas are critical emergencies in neurosurgery, and patients symptomatic from acute epidural hematomas are typically treated with rapid surgical decompression. However, some patients, if asymptomatic, may be treated with close clinical observation and serial imaging. Although rare, rapid spontaneous resolution of epidural hematomas in the pediatric population has even been reported, with only seven cases in the literature. Numerous theories have been proposed to explain the pathophysiology behind these cases, including egress of epidural collections through cranial discontinuities (fractures/open sutures), blood that originates in the subgaleal space, and bleeding from the cranial diploic cavity after a skull fracture that preferentially expands into the subgaleal space. We report the case of a rapidly resolving epidural hematoma in a 13-year-old boy. This case allows for more detailed inferences to be made concerning the nature of the epidural hematoma's resolution, as it is the first reported case in which an intracranial pressure monitor has been utilized. We also review the literature and discuss the nature of rapid spontaneous epidural hematoma resolution.
The objective of the study was to characterize the population served by the student-led Guerrilla Eye Service (GES), a mobile outreach program that delivers comprehensive ophthalmic care to underserved communities in the greater Pittsburgh area. Patients and methods: Patients attending GES missions at a single urban free clinic from 2012 through 2017 were included in this retrospective case series. All patients underwent a comprehensive eye examination at no cost, with referral to a university eye clinic if necessary. Demographic characteristics, past ocular history, reasons for attendance, and ophthalmic diagnoses were recorded. Attendance rates and treatment outcomes of patients referred to the university eye clinic were also reviewed. Results: We reviewed records of 360 GES patients (mean age 43 years, age range 1-79 years; 56% [200] male; 37% [133] non-English speakers). The most common reasons for attending were blurry vision (28% [101]), need for new glasses (22% [80]), and referral for a diabetic eye exam (18% [63]). The most common diagnosis made was refractive error (59% [214]), and vouchers for free spectacles were provided. One-third of diabetic patients had retinopathy (32% [38]). Glaucoma suspect (11% [40]), narrow angles (4% [13]), treatment-requiring diabetic eye disease (4% [14]), and visually-significant cataract (3% [11]) were diagnoses that most often prompted referral to the university clinic. In all, 114 patients were referred (32%), of whom 82 (72%) attended the follow-up visit. Other patients continued to receive longitudinal care through GES. Conclusion: Medical student-led outreach programs under the supervision of an attending ophthalmologist can deliver regular eye care to underserved communities while providing referrals to a university clinic for those with advanced disease.
Aqueous tear-deficient dry eye is a multifactorial chronic disorder in which the lacrimal glands fail to produce enough tears to maintain a healthy ocular surface. The existence of lacrimal gland stem/progenitor cells was proposed in several species, yet their origin and characteristics are not very clear. Here, we investigated the presence of resident progenitor cells and their regenerative potential in a rabbit model with lacrimal gland main excretory duct ligation-induced injury. The ligation-injured lacrimal glands temporarily decreased in weight and had impaired tear secretion. Protein expression profiles and transcriptional profiles were obtained from injured tissue. Isolated lacrimal gland progenitor cells were tested and characterized by stem cell-related marker evaluation, single cell clonal assay and three-dimensional (3-D) culture. The results of our study indicate that lacrimal glands are capable of tissue repair after duct ligation-induced injury, likely involving resident stem/progenitor cells and epithelial-mesenchymal transitions. Lacrimal gland progenitor cells isolated from ligated tissue can differentiate in 3-D culture. The results provide further insights into lacrimal gland stem/progenitor cell physiology and their potential for treating severe cases of tear deficiency.
Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5 0 mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs formation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α-another key target of regulation-occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control.
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