Reduced Incidence of Pneumothorax and Chest Tube Placement following Transthoracic CT-Guided Lung Biopsy with Gelatin Sponge Torpedo Track Embolization: A Propensity Score-Matched Study.

Objectives: To evaluate the effectiveness of track embolization using gelatin sponge torpedo in reducing the incidence of pneumothorax and chest tube placement after percutaneous CT-guided lung biopsy. Methods: A retrospective single-center analysis of percutaneous computed tomography (CT)-guided transthoracic lung biopsies was performed between 2017 and 2022. After excluding the patients who received an ultrasound-guided biopsy, combined lung biopsy with ablation, fiducial placement, unsuccessful procedure due to uncooperative patient, and age under 18 years, 884 patients' clinical information was collected (667 without track embolization and 217 with track embolization). The incidence of early and late pneumothorax and chest tube placement were compared between the two groups. Propensity score matching (PSM) was applied to minimize selection bias. Univariable and multivariable analyses were performed to determine risk factors for pneumothorax. Results: After PSM, the baseline differences and all factors that could affect the incidence of pneumothorax were balanced between the track embolization group (217 patients) and the non-track embolization group (217 patients). The incidence rates of early pneumothorax (13.4% vs. 24.0% p = 0.005), late pneumothorax (11.0% vs. 18.0% p = 0.021), and chest tube placement (0.9% vs. 4.6% p = 0.036) were significantly decreased in the track embolization group. However, the success rate of tissue diagnosis yield and length of hospital stay were not significantly different between the two groups. In multivariate analysis, the risk of pneumothorax increased as the fissure was passed (OR = 3.719, p = 0.027). Conclusions: Using track embolization with a gelatin sponge torpedo significantly decreased the incidence of pneumothorax and chest tube placement following percutaneous CT-guided lung biopsy.

Electron-translucency and partial defects of synaptic basal lamina in the electrocyte synapse of an electric ray (Narke japonica) in 3D embedment-free section electron microscopy.

The synaptic basal lamina of the electrocytes was disclosed to be electron-translucent to some extent when viewed in an en-face direction in embedment-free section transmission electron microscopy (EFS-TEM), and synaptic vesicles located close to the presynaptic membrane were seen through the synaptic basal lamina together with the presynaptic and postsynaptic membranes. This feature of translucency has the potential to analyze possible spatial interrelations in situ between bioactive molecules in the synaptic basal lamina and the synaptic vesicles in further studies. The synaptic basal lamina, appearing as an electron-dense line sandwiched by two parallel lines representing the presynaptic and postsynaptic membranes in ultrathin sections cut right to the synaptic junctional plane in conventional TEM, was not fully continuous but randomly intermittent along its trajectory. Compatible with the intermittent line appearance, the en-face 3D view in embedment-free section TEM revealed for the first time partial irregular defects of the synaptic basal lamina. Considering the known functional significance of several molecules contained in the synaptic basal lamina in the maintenance and exertion of the synapse, its partial defects may not represent its rigid structural features, but its immature structure under remodeling or its dynamic changes in consistency such as the sol/gel transition, whose validity needs further examination. RESEARCH HIGHLIGHTS: In embedment-free section TEM, a 3D en-face view of synaptic basal lamina in situ is reliably possible. The basal lamina en-face is electron-translucent, which makes it possible to analyze spatial interrelation between pre- and post-synaptic components. Partial irregular defects in the basal lamina are revealed in Torpedo electrocytes, suggesting its remodeling or dynamic changes in consistency.

Type 1 and type 2 torpedo maculopathy.

PURPOSE: To analyze torpedo maculopathy (TM) and to report the characteristics of the disease. METHODS: Retrospective study. The review of a database for clinical diagnosis identified eight patients with TM lesions in the retina between 2016 and 2022. Multimodal imaging was used to analyze the cases. RESULTS: All cases were unilateral, asymptomatic, and hypopigmented. They were associated by surrounding hyperpigmented retinal pigment epithelium changes to varying degrees. All lesions were located in the temporal retina on the horizontal axis, pointing towards the fovea, except for one patient with a lesion inferior to the fovea. Optical coherence tomography imaging revealed a normal inner retina in all eyes. In the area of the TM lesion, attenuation of the interdigitation zone was seen in mild cases (three cases). All other five patients had thinning of the outer nuclear layer and loss of ellipsoid zone and interdigitation zone of the TM lesion. Four of these cases had a subretinal cavitation/cleft, and two of them additionally an inner choroidal excavation. No patient had any sign of choroidal neovascularization. The average age for patients with type 1 TM was 18 years and for type 2 TM 16.5 years. CONCLUSION: In this large case series, we could not detect an age difference between the different types of the TM. Contrary to previous discussions, type 2 TM can also occur in young patients.

Long-term follow-up of torpedo maculopathy: a case series and mini-review.

BACKGROUND: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition. CASE REPORTS: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected. CONCLUSIONS: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome.

Association of torpedo maculopathy and keratoconus in a young patient: A multimodal imaging study.

PURPOSE: To report and document a case of torpedo maculopathy found in a patient affected by keratoconus.Case report: An healthy 16-year-old male patient, affected by keratoconus in both eyes, was referred to the cornea service of our hospital for a follow-up visit.During the dilated fundus examination of the left eye, an oval, well-demarcated, hypopigmented lesion was observed in the juxtafoveal temporal region, pointing towards the center of the macula. Multimodal imaging of the lesion was performed, and the diagnosis of Torpedo Maculopathy was established based on the clinical picture. CONCLUSION: This is the first case of torpedo maculopathy described in a patient affected by keratoconus. This association may be merely fortuitous or the result of developmental abnormalities affecting both corneal and retinal structures.

Identification of the native Torpedo californica nicotinic acetylcholine receptor's glycan composition after a multi-step sequential purification method using MALDI-ToF MS.

The Cys-loop pentameric ligand-gated ion channels comprise a dynamic group of proteins that have been extensively studied for decades, yielding a wealth of findings at both the structural and functional levels. The nicotinic acetylcholine receptor (nAChR) is no exception, as it is part of this large protein family involved in proper organismal function. Our efforts have successfully produced a highly pure nAChR in detergent complex (nAChR-DC), enabling more robust studies to be conducted on it, including beginning to experiment with high-throughput crystallization. Our homogeneous product has been identified and extensively characterized with 100% identity using Nano Lc MS/MS and MALDI ToF/ToF for each nAChR subunit. Additionally, the N-linked glycans in the Torpedo californica-nAChR (Tc-nAChR) subunits have been identified. To study this, the Tc-nAChR subunits were digested with PNGase F and the released glycans were analyzed by MALDI-ToF. The MS results showed the presence of high-mannose N-glycan in all native Tc-nAChR subunits. Specifically, the oligommanose population Man8-9GlcNac2 with peaks at m/z 1742 and 1904 ([M + Na]+ ions) were observed.

A rare case of hyperpigmented torpedo maculopathy.

PURPOSE: To describe a rare presentation of torpedo maculopathy (TM). CASE DESCRIPTION: A 25-year-old male was examined in the retina clinic for a macular scar in the left eye. His visual acuity was 20/20, N6 in both eyes and no past history of ocular trauma or any medical or ocular history. The anterior segment was quiet and intraocular pressure was normal. RESULTS: The patient's left eye on 78D slit lamp biomicroscopy revealed a flat, diffusely hyperpigmented fusiform torpedo-like lesion with sharp margins and surrounding hypopigmentation located predominantly temporal to the fovea, with its tip pointing towards it and just crossing the vertical foveal midline. Dilated fundus examination with binocular indirect ophthalmoscopy revealed no peripheral chorioretinal lesions or vitritis in both eyes. OCT scan through the lesion revealed gross damage to the outer retinal layers, as well as thickening of the retinal pigment epithelium and underlying shadowing, as well as a hyporeflective subretinal cleft involving the lesion. OCT also revealed outer retinal layer damage with an intact retinal pigment epithelium through the lesion's hypopigmented margins. Fundus autofluorescence image revealed a globally hypoautofluorescent lesion in the left eye, with surrounding patchy hyperautofluoroscent areas. Based on the patient history, clinical and imaging findings, other differential diagnoses such as atypical congenital hypertrophy of retinal pigment epithelium (RPE), choroidal nevus, RPE hamartoma, trauma and inflammatory conditions were ruled out. The diagnosis of TM was confirmed based on the typical lesion shape and location. CONCLUSION: A torpedo lesion with diffuse hyperpigmentation is an unusually rare presentation.

A unique presentation of subretinal fluid in a type III torpedo maculopathy phenotype.

Purpose: To report a rare type III torpedo maculopathy lesion with a unique manifestation of subretinal fluid. Observations: A nine-year-old patient was referred to retina for an evaluation of a hypopigmented oval-shaped lesion in the temporal macula with an area of inferior subretinal fluid in the right eye. The lesion demonstrated inner and outer retinal and retinal pigment epithelial attenuation, intraretinal and subretinal fluid, a serous neurosensory retinal detachment, and inner choroidal excavation on optical coherence tomography. Fundus autofluorescence showed a lane of downward-tracking fluid. Intravenously administered fluorescein angiography revealed a window defect in the area of the torpedo lesion suggesting choroidal flush. Conclusions and Importance: The case is the third documented case of torpedo maculopathy with subretinal fluid in the literature with a unique combination of intraretinal cystic changes and dependent descending subretinal fluid, somewhat akin to a Best disease outside of the fovea with choroidal excavation. The morphology of torpedo maculopathy continues to expand as more cases are revealed.

Unusual presentation of tractional retinal detachment in beta thalassemia minor.

Purpose: To report a case of proliferative retinopathy with tractional retinal detachment associated with beta thalassemia minor in a 27-year-old female. Observations: A young lady having beta thalassemia minor presented with decreased vision in both eyes, the effect being more severe in her right eye. The patient's other systemic history, including ophthalmic history, was unremarkable. The fundus examination revealed peripheral retinal ischemia in both eyes and tractional retinal detachment in the right eye. Conclusion: Beta thalassemia minor is not associated with striking retinal pathology, nevertheless proliferative retinopathy. However, in this case the patient developed tractional retinal detachment that required surgery. This indicates that proliferative changes may develop in patients with beta thalassemia, and routine fundus examinations could be recommended for these patients.

Torpedo Maculopathy. A Case Report.

AIM: Torpedo maculopathy is an incidental, congenital retinal lesion. The typical clinical finding is a unilateral, symmetric, oval, hypopigmented lesion in the inferotemporal macula. In most cases, the lesion is along the horizontal raphe, is torpedo-shaped, and the nasal edge is directed into the foveola. The diagnosis is determined on the basis of its characteristic shape, localization and findings on optical coherence tomography (OCT). The etiology and pathogenesis of torpedo maculopathy is unclear, but it is believed to be a congenital defect of the retinal pigment epithelium (RPE). The aim of this publication is  highlight this diagnosis and to present an incidental finding of torpedo maculopathy in an adult patient. CASE REPORT: A 30-year-old female patient reported for a routine eye examination. Fundus examination of the right eye revealed an oval hypopigmented lesion with a size of 1 disk diameter inferotemporally from the fovea, which was followed by a satellite lesion in the same axis directed into the foveola. Based on OCT, OCT angiography, fundus autofluorescence, and the typical shape and location of the lesion, the patient was diagnosed with torpedo maculopathy in the right eye. CONCLUSION: In general, torpedo maculopathy is an asymptomatic, congenital, benign retinal lesion, which is mostly diagnosed accidentally during a routine fundus examination. TM is non-progressive retinal finding with a minimal risk of deterioration of visual functions, which does not require any treatment. Nevertheless, due to the rare risk of a choroidal neovascular membrane, it is recommended to examine patients once a year. It is necessary to consider this diagnosis when a unilateral hypopigmented lesion is found inferotemporally from the fovea, and to distinguish it from chorioretinal atrophy, scar, vitelliform dystrophy, or other RPE lesions as part of the differential diagnosis.

DNA-directed termination of RNA polymerase II transcription.

RNA polymerase II (RNAPII) transcription involves initiation from a promoter, transcriptional elongation through the gene, and termination in the terminator region. In bacteria, terminators often contain specific DNA elements provoking polymerase dissociation, but RNAPII transcription termination is thought to be driven entirely by protein co-factors. We used biochemical reconstitution, single-molecule studies, and genome-wide analysis in yeast to study RNAPII termination. Transcription into natural terminators by pure RNAPII results in spontaneous termination at specific sequences containing T-tracts. Single-molecule analysis indicates that termination involves pausing without backtracking. The "torpedo" Rat1-Rai1 exonuclease (XRN2 in humans) greatly stimulates spontaneous termination but is ineffectual on other paused RNAPIIs. By contrast, elongation factor Spt4-Spt5 (DSIF) suppresses termination. Genome-wide analysis further indicates that termination occurs by transcript cleavage at the poly(A) site exposing a new 5' RNA-end that allows Rat1-Rai1 loading, which then catches up with destabilized RNAPII at specific termination sites to end transcription.

I Like This New Me: Unravelling Population Structure of Mediterranean Electric Rays and Taxonomic Uncertainties within Torpediniformes.

The present study focused on the three species of electric rays known to occur in the Mediterranean Sea: Torpedo torpedo, Torpedo marmorata and Tetronarce nobiliana. Correct identification of specimens is needed to properly assess the impact of fisheries on populations and species. Unfortunately, torpedoes share high morphological similarities, boosting episodes of field misidentification. In this context, genetic data was used (1) to identify specimens caught during fishing operations, (2) to measure the diversity among and within these species, and (3) to shed light on the possible occurrence of additional hidden species in the investigated area. New and already published sequences of COI and NADH2 mitochondrial genes were analyzed, both at a small scale along the Sardinian coasts (Western Mediterranean) and at a large scale in the whole Mediterranean Sea. High levels of genetic diversity were found in Sardinian populations, being significantly different from other areas of the Eastern Mediterranean Sea due to the biotic and abiotic factors here discussed. Sardinian torpedoes can hence be indicated as priority populations/areas to be protected within the Mediterranean Sea. Moreover, sequence data confirmed that only the three species occur in the investigated area. The application of several 'species-delimitation' methods found evidence of cryptic species in the three species outside the Mediterranean Sea, as well as in other genera/families, suggesting the urgent need for future studies and a comprehensive revision of the order Torpediniformes for its effective conservation.

Fin systems comparative anatomy in model Batoidea Raja asterias and Torpedo marmorata: Insights and relatioships between musculo-skeletal layout, locomotion and morphology.

The macroscopic and microscopic morphology of the appendicular skeleton was studied in the two species Raja asterias (order Rajiformes) and Torpedo marmorata (Order Torpediniformes), comparing the organization and structural layout of pectoral, pelvic, and tail fin systems. The shape, surface area and portance of the T. marmorata pectoral fin system (hydrodynamic lift) were conditioned by the presence of the two electric organs in the disk central part, which reduced the pectoral fin surface area, suggesting a lower efficiency of the "flapping effectors" than those of R. asterias. Otherwise, radials' rays alignment, morphology and calcification pattern showed in both species the same structural layout characterized in the fin medial zone by stiffly paired columns of calcified tiles in the perpendicular plane to the flat batoid body, then revolving and in the horizontal plane to continue as separate mono-columnar rays in the fin lateral zone with a morphology suggesting fin stiffness variance between medial/lateral zone. Pelvic fins morphology was alike in the two species, however with different calcified tiles patterns of the 1st compound radial and pterygia in respect to the fin-rays articulating perpendicularly to the latter, whose tile rows lay-out was also different from that of the pectoral fins radials. The T. marmorata tail-caudal fin showed a muscular and connective scaffold capable of a significant oscillatory forward thrust. On the contrary, the R. asterias dorsal tail fins were stiffened by a scaffold of radials-like calcified segments. Histomorphology, heat-deproteination technique and morphometry provided new data on the wing-fins structural layout which can be correlated to the mechanics of the Batoid swimming behavior and suggested a cartilage-calcification process combining interstitial cartilage growth (as that of all vertebrates anlagen) and a mineral deposition with accretion of individual centers (the tiles). The resulting layout showed scattered zones of un-mineralized matrix within the calcified mass and a less compact texture of the matrix calcified fibers suggesting a possible way of fluid diffusion throughout the mineralized tissue. These observations could explain the survival of the embedded chondrocytes in absence of a canalicular system as that of the cortical bone.

Assessment of Purity, Functionality, Stability, and Lipid Composition of Cyclofos-nAChR-Detergent Complexes from Torpedo californica Using Lipid Matrix and Macroscopic Electrophysiology.

The main objective of the present study was to find detergents that can maintain the functionality and stability of the Torpedo californica nicotinic acetylcholine receptor (Tc-nAChR). We examined the functionality, stability, and purity analysis of affinity-purified Tc-nAChR solubilized in detergents from the Cyclofos (CF) family [cyclofoscholine 4 (CF-4), cyclofoscholine 6 (CF-6), and cyclofloscholine 7 (CF-7)]. The functionality of the CF-Tc-nAChR-detergent complex (DC) was evaluated using the Two Electrode Voltage Clamp (TEVC) method. To assess stability, we used the florescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) methodology. We also performed a lipidomic analysis using Ultra-Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS) to evaluate the lipid composition of the CF-Tc-nAChR-DCs. The CF-4-Tc-nAChR-DC displayed a robust macroscopic current (- 200 ± 60 nA); however, the CF-6-Tc-nAChR-DC and CF-7-Tc-nAChR-DC displayed significant reductions in the macroscopic currents. The CF-6-Tc-nAChR and CF-4-Tc-nAChR displayed higher fractional florescence recovery. Addition of cholesterol produced a mild enhancement of the mobile fraction on the CF-6-Tc-nAChR. The lipidomic analysis revealed that the CF-7-Tc-nAChR-DC displayed substantial delipidation, consistent with the lack of stability and functional response of this complex. Although the CF-6-nAChR-DC complex retained the largest amount of lipids, it showed a loss of six lipid species [SM(d16:1/18:0); PC(18:2/14:1); PC(14:0/18:1); PC(16:0/18:1); PC(20:5/20:4), and PC(20:4/20:5)] that are present in the CF-4-nAChR-DC. Overall, the CF-4-nAChR displayed robust functionality, significant stability, and the best purity among the three CF detergents; therefore, CF-4 is a suitable candidate to prepare Tc-nAChR crystals for structural studies.

Expanded Spectrum Torpedo Retinopathy: A Case Series.

Torpedo lesions in the retina are rare, and their clinical significance has not been well established. This case series highlights patients with atypical torpedo lesions with varying orientations and pigmentation patterns. We describe the first documented case of an inferiorly oriented lesion, to our knowledge, and add to the few previous descriptions of double-torpedo lesions.

Multimodal Imaging of Choroidal Structural in Torpedo Maculopathy.

Objective: To report a case of torpedo maculopathy with multimodal fundus imaging methods, and apply the choroid vascularity index to quantitatively describe the choroidal structural changes in torpedo maculopathy. Case presentation: An asymptomatic 41-year-old Chinese woman with an incidentally found yellowish-white macular lesion in her left eye was referred to our hospital. She was unaware of any prior medical conditions. The best corrected visual acuity (BCVA) was 20/20 OD and 20/25 OS, respectively. Fundus exam of her left eye revealed a well-circumscribed torpedo-like hypopigmented lesion in the macula region, and the tapered edge directed toward the fovea. Pigment deposition could be seen in the inferotemporal portion of the torpedo lesion. Fluorescein angiography showed the corresponding window defect without leakage and fundus autofluorescence demonstrated low signal throughout the lesion. Enhanced depth imaging optical coherence tomography revealed outer retinal attenuation, subretinal cavitation, subtle inner choroidal excavation and thinning of outer nuclear layer. The diagnosis of torpedo maculopathy was clinically made. Choroidal vascularity index (CVI) and sub-foveal choroidal thickness (SFCT) were applied to display changes of choroidal structure. The results implied that both subfoveal CVI and SFCT of the affected eye seemed relatively lower when compared with the fellow eye. Optical coherence tomography angiography showed reduced density of the choriocapillaris in the temporal area of the lesion and increased capillary density in the nasal area. Functional examinations, including microperimetry, multifocal electroretinogram and static perimetry also revealed reduced retinal sensitivity, decreased stimulated amplitude and suspected scotoma in the lesion area. After 12 months of follow-up, the patient's visual acuity and the clinical appearance of the lesion were unchanged. Conclusion: The torpedo maculopathy may be identified by abnormal appearance with multimodal imaging. Decreased choroidal vascularity in the lesion area measured quantitatively by choroid vascularity index may play a role in pathogenesis of torpedo maculopathy.

Multimodal imaging of torpedo maculopathy with optical coherence tomography angiography.

A 24-year-old woman presented for routine clinical evaluation. Her best-corrected visual acuity was 20/20 and slit-lamp examination of the anterior segment was normal in both eyes. Fundus examination of the left eye revealed a hypopigmented lesion, one disc diameter temporal to the fovea, with a hyperpigmented tail extending temporally from the main lesion, consistent with a torpedo maculopathy. Fundus autofluorescence showed an hypoautofluorescence with hyperautofluorescent border. Swept-source optical coherence tomography (OCT) showed a normal inner retina and a degeneration of the outer retina without retinal cavitation. OCT angiography (OCT-A) of the choriocapillaris layer revealed reverse shadowing caused by the increased transmission from the atrophied outer retina and RPE within the torpedo lesion and attenuation of signal in the area of the temporal hyperpigmentation. The superficial capillary plexus was normal. This case includes a multimodal imaging with OCT-A of torpedo maculopathy in a Tunisian woman. Further reports are required to provide a better understanding of this rare condition.

Feeding on clean food? Potential effects of electric organ discharges by Torpedo spp. (Torpediniformes: Torpedinidae) on their trophically transmitted parasites.

Members of the Torpedinidae (torpedoes) and Hypnidae (coffin ray) use electric organ discharges (EOD) to stun or kill their prey before consumption. We investigated whether EOD could also negatively affect the helminth larvae infecting these preys through a surrogate model: we applied electric discharges to individuals of blue whiting, Micromesistius poutassou, that harbored live larvae of Anisakis. Larval mortality throughout a 6-h period was significantly higher in the treatment group, suggesting that EODs could significantly hamper helminth recruitment. We then tested whether torpedinids and hypnids ("strong-EOD" families) harbored species-poor helminth (cestode) assemblages compared with "weak-EOD" Torpediniformes (Narcidae and Narkidae) and other Batoidea. Based on comparisons on estimated species diversity and mean species richness of tapeworms at host individual level we found that (i) Torpediniformes had the lowest tapeworm diversity of all Batoidea orders; (ii) Torpedo spp. consistently had the lowest mean cestode richness at host individual level, and this could not be related to other host factors influencing cestode diversity in chondrichthyans, that is body size, trophic level or dietary breath. However, a preliminary comparison between "strong-EOD" and "weak-EOD" Torpediniformes did not detect clear differences of cestode richness. Thus, evidence supporting an unambiguous contribution of EODs to depauperate cestode assemblages requires further research.

Multimodal Imaging of Torpedo Maculopathy With Fluorescence Adaptive Optics Imaging of Individual Retinal Pigmented Epithelial Cells.

Torpedo maculopathy (TM) is a rare congenital defect of the retinal pigment epithelium (RPE). The RPE is often evaluated clinically using fundus autofluorescence (AF), a technique that visualizes RPE structure at the tissue level from the intrinsic AF of RPE fluorophores. TM lesions typically emit little or no AF, but this macroscopic assessment is unable to resolve the RPE cells, leaving the organization of the RPE cell mosaic in TM unknown. We used fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to show here for the first time the microscopic cellular-level structural alterations to the RPE cell mosaic in TM that underlie the tissue-level changes seen in conventional clinical imaging. We evaluated two patients with TM using conventional clinical imaging techniques and adaptive optics (AO) infrared autofluorescence (IRAF) in AOSLO. Confocal AOSLO revealed relatively normal cones outside the TM lesion but altered cone appearance within it and along its margins in both patients. We quantified cone topography and RPE cell morphometry from the fovea to the margin of the lesion in case 1 and found cone density to be within the normal range across the locations imaged. However, RPE morphometric analysis revealed disrupted RPE cells outside the margin of the lesion; the mean RPE cell area was greater than two standard deviations above the normative range up to approximately 1.5 mm from the lesion margin. Similar morphometric changes were seen to individual RPE cells in case 2. Multi-modal imaging with AOSLO reveals that RPE cells are abnormal in TM well beyond the margins of the characteristic TM lesion boundary defined with conventional clinical imaging. Since the TM fovea appears to be fully formed, with normal cone packing, it is possible that the congenital RPE defect in TM occurs relatively late in retinal development. This work demonstrates how cellular level imaging of the RPE can provide new insight into RPE pathologies, particularly for rare conditions such as TM.

Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades.

Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field.