@article {775, title = {Infrared imaging and optical coherence tomography reveal early-stage astrocytic hamartomas not detectable by fundoscopy.}, journal = {Am J Ophthalmol}, volume = {153}, year = {2012}, month = {2012 May}, pages = {883-889.e2}, abstract = {

PURPOSE: To describe and correlate the features of astrocytic hamartomas using multimodal imaging.

DESIGN: Prospective, noncomparative, observational case series.

METHODS: This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared.

RESULTS: In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots.

CONCLUSIONS: Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.

}, keywords = {Adolescent, Astrocytes, Child, Diagnostic Imaging, Female, Fluorescein Angiography, Humans, Infrared Rays, Male, Ophthalmoscopes, Prospective Studies, Retinal Neoplasms, Tomography, Optical Coherence, Tuberous Sclerosis}, issn = {1879-1891}, doi = {10.1016/j.ajo.2011.10.033}, author = {Xu, Luna and Burke, Tomas R and Greenberg, Jonathan P and Mahajan, Vinit B and Tsang, Stephen H} } @article {827, title = {Thrombin receptor signaling to cytoskeleton requires Hsp90.}, journal = {J Biol Chem}, volume = {276}, year = {2001}, month = {2001 Aug 31}, pages = {32642-7}, abstract = {

Thrombin is a serine protease that evokes various cellular responses involved in injury and repair of the nervous system through the activation of protease-activated receptor-1 (PAR-1). Signals that modulate cell morphology precede most PAR-1 effects, but the initial signal transduction molecules are not known. Using the yeast two-hybrid system, we identified Hsp90, a chaperone with known signaling properties, as a binding partner of PAR-1. The interaction was confirmed by glutathione S-transferase pull-down, overlay, and co-immunoprecipitation assays. Morphological assays in mouse astrocytes were carried out to evaluate the importance of Hsp90 during cytoskeletal signaling. Reducing Hsp90 levels by antisense treatment or disruption of the Hsp90.PAR-1 complex by the Hsp90-specific drug geldanamycin attenuated thrombin-mediated astrocyte shape changes. Furthermore, overexpression of the PAR-1 cytoplasmic tail abrogated thrombin-induced cytoskeletal changes in neuronal cells. Treatment with geldanamycin specifically inhibited activation of RhoA without affecting thrombin-mediated intracellular calcium release, revealing the regulation of a distinct signaling pathway by Hsp90. Taken together, these studies demonstrate that Hsp90 may be essential for PAR-1-mediated signaling to the cytoskeleton.

}, keywords = {Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Cerebral Cortex, Cloning, Molecular, Cytoskeleton, HSP90 Heat-Shock Proteins, Humans, Neurons, Oligodeoxyribonucleotides, Antisense, Rats, Rats, Sprague-Dawley, Receptor, PAR-1, Receptors, Thrombin, Recombinant Fusion Proteins, rhoA GTP-Binding Protein, Saccharomyces cerevisiae, Signal Transduction, Thrombin}, issn = {0021-9258}, doi = {10.1074/jbc.M104212200}, author = {Pai, K S and Mahajan, V B and Lau, A and Cunningham, D D} }