Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma.
*Axonal Transport/physiology; *bouton; *mitochondria; *neurodegeneration; *retinal; *RRID:IMSRJAX:000671; *RRID:IMSRJAX:007048; *RRID:SCR002716; *RRID:SCR002865; *superior colliculus; *synapse; Animal; Animals; Disease Models; Electron; Glaucoma/metabolism/*pathology; Imaging; Inbred DBA; Mice; Microscopy; Mitochondria/pathology; Neuroanatomical Tract-Tracing Techniques; Regression Analysis; Retinal Ganglion Cells/metabolism/*pathology; Scanning; Superior Colliculi/metabolism/*pathology; Synapses/metabolism/*pathology; Three-Dimensional; Visual Pathways/metabolism/pathology
Axonal transport defects are an early pathology occurring within the retinofugal projection of the DBA/2J mouse model of glaucoma. Retinal ganglion cell (RGC) axons and terminals are detectable after transport is affected, yet little is known about the condition of these structures. We examined the ultrastructure of the glaucomatous superior colliculus (SC) with three-dimensional serial block-face scanning electron microscopy to determine the distribution and morphology of retinal terminals in aged mice exhibiting varying levels of axonal transport integrity. After initial axonal transport failure, retinal terminal densities did not vary compared with either transport-intact or control tissue. Although retinal terminals lacked overt signs of neurodegeneration, transport-intact areas of glaucomatous SC exhibited larger retinal terminals and associated mitochondria. This likely indicates increased oxidative capacity and may be a compensatory response to the stressors that this projection is experiencing. Areas devoid of transported tracer label showed reduced mitochondrial volumes as well as decreased active zone number and surface area, suggesting that oxidative capacity and synapse strength are reduced as disease progresses but before degeneration of the synapse. Mitochondrial volume was a strong predictor of bouton size independent of pathology. These findings indicate that RGC axons retain connectivity after losing function early in the disease process, creating an important therapeutic opportunity for protection or restoration of vision in glaucoma. J. Comp. Neurol. 524:3503-3517, 2016. (c) 2016 Wiley Periodicals, Inc.
Smith Matthew A; Xia Christina Z; Dengler-Crish Christine M; Fening Kelly M; Inman Denise M; Schofield Brett R; Crish Samuel D
The Journal of comparative neurology
2016
2016-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/cne.24012" target="_blank" rel="noreferrer noopener">10.1002/cne.24012</a>
Early astrocyte redistribution in the optic nerve precedes axonopathy in the DBA/2J mouse model of glaucoma.
*Astrocyte; *Axonopathy; *Glaucoma; *Gliosis; *Neurodegeneration; *Retinal ganglion cell; Animal; Animals; Astrocytes/*pathology; Axons/pathology; Disease Models; Glaucoma; Imaging; Inbred DBA; Mice; Nerve Degeneration/etiology/*pathology; Open-Angle/*pathology; Optic Nerve Diseases/etiology/*pathology; Optic Nerve/*pathology; Photomicrography; Retinal Ganglion Cells/*pathology; Three-Dimensional; Time Factors
Glaucoma challenges the survival of retinal ganglion cell axons in the optic nerve through processes dependent on both aging and ocular pressure. Relevant stressors likely include complex interplay between axons and astrocytes, both in the retina and optic nerve. In the DBA/2J mouse model of pigmentary glaucoma, early progression involves axonopathy characterized by loss of functional transport prior to outright degeneration. Here we describe novel features of early pathogenesis in the DBA/2J nerve. With age the cross-sectional area of the nerve increases; this is associated generally with diminished axon packing density and survival and increased glial coverage of the nerve. However, for nerves with the highest axon density, as the nerve expands mean cross-sectional axon area enlarges as well. This early expansion was marked by disorganized axoplasm and accumulation of hyperphosphorylated neurofilamants indicative of axonopathy. Axon expansion occurs without loss up to a critical threshold for size (about 0.45-0.50 mum(2)), above which additional expansion tightly correlates with frank loss of axons. As well, early axon expansion prior to degeneration is concurrent with decreased astrocyte ramification with redistribution of processes towards the nerve edge. As axons expand beyond the critical threshold for loss, glial area resumes an even distribution from the center to edge of the nerve. We also found that early axon expansion is accompanied by reduced numbers of mitochondria per unit area in the nerve. Finally, our data indicate that both IOP and nerve expansion are associated with axon enlargement and reduced axon density for aged nerves. Collectively, our data support the hypothesis that diminished bioenergetic resources in conjunction with early nerve and glial remodeling could be a primary inducer of progression of axon pathology in glaucoma.
Cooper Melissa L; Crish Samuel D; Inman Denise M; Horner Philip J; Calkins David J
Experimental eye research
2016
2016-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.exer.2015.11.016" target="_blank" rel="noreferrer noopener">10.1016/j.exer.2015.11.016</a>
Dynamic tracking influenced by anatomy in patellar instability.
Adult; Articular; Female; Femur/diagnostic imaging; Humans; Imaging; Joint Instability/*diagnostic imaging; Knee Joint/*diagnostic imaging; Male; Patella/*diagnostic imaging; Patellar Dislocation/*diagnostic imaging; Patellar instability; Patellar tracking; Range of Motion; Recurrence; Three-Dimensional; Tibia/diagnostic imaging; Tibial tuberosity; Tomography; Trochlear dysplasia; X-Ray Computed; Young Adult
BACKGROUND: The current study was performed to correlate anatomical parameters related to trochlear dysplasia, tibial tuberosity position, and patella alta with in vivo patellar tracking for subjects with recurrent patellar instability. METHODS: Eight subjects with recurrent patellar instability that failed conservative treatment were evaluated using computational reconstruction of in vivo knee motion. Computational models were created from dynamic CT scans of the knee during extension against gravity. Shape matching techniques were utilized to position a single model of each bone (femur, patella and tibia) to represent multiple positions of knee extension. Patellar tracking was characterized by the bisect offset index (lateral shift) and lateral tilt. Anatomical parameters were characterized by the inclination of the lateral ridge of the trochlear groove, the lateral distance from the tibial tuberosity to the posterior cruciate ligament attachment (lateral TT-PCL distance), and the Caton-Deschamps index. Stepwise multivariable linear regression analysis was used to relate patellar tracking to the anatomical parameters at low (\textless20 degrees ) and high flexion angles. RESULTS: At low flexion angles, both lateral trochlear inclination and lateral TT-PCL distance were significantly correlated with bisect offset index (p=0.02). Only lateral trochlear inclination was significantly correlated with lateral tilt (p\textless0.001). At high flexion angles, bisect offset index and lateral tilt were correlated with only lateral TT-PCL distance (p
Elias John J; Soehnlen Neil T; Guseila Loredana M; Cosgarea Andrew J
The Knee
2016
2016-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.knee.2016.01.021" target="_blank" rel="noreferrer noopener">10.1016/j.knee.2016.01.021</a>
Contributions of paleorheumatology to understanding contemporary disease.
Humans; Animals; Immunohistochemistry; Body Temperature; Phylogeny; Osteoarthritis/pathology; Radiography; Fossils; Bone Remodeling; DNA; DNA/genetics/isolation & purification; *Paleopathology/instrumentation/methods; *Rheumatology; Bone and Bones/chemistry/diagnostic imaging/immunology; Bone Diseases/*pathology; Collagen/immunology/isolation & purification; Dinosaurs; Gout/pathology; Joint Diseases/*pathology; Mammals; Microscopy/methods; Rheumatic Diseases/pathology; Imaging; Arthritis; Three-Dimensional; Sequence Analysis; Infectious/pathology; Reactive/pathology
As paleopathology has evolved from observational speculation to analysis of testable hypotheses, so too has recognition of its contribution to vertebrate paleontology. In the presence of significant structural and density variation (between matrix and osseous structures), x-rays provide an additional perspective of osseous response to stress and disease. As film techniques are time and cost expensive, fluoroscopy has proven a valuable alternative. Radiologic techniques also allow non-invasive "sectioning" of specimens, illustrating significant internal detail. The object can be "split" on a plane and the two portions rotated to "open" the image. This three-dimensional approach now can be applied to other forms of sequential data to their facilitate 3-dimensional representation graphically or with solid representations. Antigen and microstructure may be well preserved in fossils. Molecular preservation with retention of helical structure and sensitivity to collagenase has been demonstrated in 10,000 year old collagen. Antigen has been extracted from 100 million year old bone and documented, in situ, in 11,000 year old bone. If the appropriate site in the tissue is assessed, if antigen is still present, and if the appropriate antisera is utilized, fixation of the antibody to the specimen can be detected. Minute amounts of DNA can be amplified and analyzed. Recovery of DNA from a 40,000 year old mammoth, 17,000 year old bison and from 25 million year old insects provides opportunity for cloning and independent assessment of relationships. Implications of available technology focuses direction for development of collaborative approaches.
Rothschild B
Reumatismo
2002
2002-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.4081/reumatismo.2002.272" target="_blank" rel="noreferrer noopener">10.4081/reumatismo.2002.272</a>
Evaluation of the FUSION-X-US-II prototype to combine automated breast ultrasound and tomosynthesis
Imaging; Ultrasonography; Mammography; mammary; Early detection of cancer; Multimodal imaging; three-dimensional
Objective The FUSION-X-US-II prototype was developed to combine 3D automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device. We evaluated the performance of ABUS and tomosynthesis in a single examination in a clinical setting. Methods In this prospective feasibility study, digital breast tomosynthesis and ABUS were performed using the FUSION-X-US-II prototype without any change of the breast position in patients referred for clarification of breast lesions with an indication for tomosynthesis. The tomosynthesis and ABUS images of the prototype were interpreted independently from the clinical standard by a breast diagnostics specialist. Any detected lesion was classified using BI-RADS (R) scores, and results of the standard clinical routine workup (gold standard) were compared to the result of the separate evaluation of the prototype images. Image quality was rated subjectively and coverage of the breast was measured. Results One hundred one patients received both ABUS and tomosynthesis using the prototype. The duration of the additional ABUS acquisition was 40 to 60 s. Breast coverage by ABUS was approximately 80.0%. ABUS image quality was rated as diagnostically useful in 86 of 101 cases (85.1%). Thirty-three of 34 malignant breast lesions (97.1%) were identified using the prototype. Conclusion The FUSION-X-US-II prototype allows a fast ABUS scan in combination with digital breast tomosynthesis in a single device integrated in the clinical workflow. Malignant breast lesions can be localized accurately with direct correlation of ABUS and tomosynthesis images. The FUSION system shows the potential to improve breast cancer screening in the future after further technical improvements.
Schaefgen B; Juskic M; Radicke M; Hertel M; Barr R; Pfob A; Togawa R; Nees J; von Au A; Fastner S; Harcos A; Gomez C; Stieber A; Riedel F; Hennigs A; Sohn C; Heil J; Golatta M
European Radiology
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s00330-020-07573-3" target="_blank" rel="noreferrer noopener">10.1007/s00330-020-07573-3</a>