Smad7 has recently been identified as a player that antagonizes transforming growth factor β (TGF-β) signals by acting downstream of TGF-β receptors. TGF-β rapidly induces expression of Smad7 mRNA in a variety of cell types, suggesting participation in a negative feedback loop to control TGF-β responses. We have previously described the genomic locus of rat Smad7 including the promoter region. Here we report polymerase chain reaction cloning of the corresponding promoter regions of human and murine Smad7 genes and functional characterization of the rat Smad7 promoter. Using transient transfection experiments of HepG2 cells, we identified the TGF-β response element within a strongly conserved region, containing a perfect Smad binding element (SBE; GTCTAGAC). Performing electrophoretic mobility shift assay and cotransfection experiments, we were able to delineate DNA-binding complexes and identified Smad3, Smad4, and Smad2. Mutation of the SBE completely abolished TGF-β inducibility of Smad7 in HepG2 cells, indicating that this sequence is necessary for TGF-β-induced transcription. Furthermore, a 3-base pair adjacent E-box is additionally essential for TGF-β-dependent promoter activation and an overlapping AP1 site is also involved. We conclude that regulation of Smad7 transcription by TGF-β is mediated via a specific constellation of recognition motifs localized around the SBE, which is conserved in human, rat, and murine genes.

To delineate pathologic changes in retinal cross sections obtained with spectral (Fourier) domain optical coherence tomography (SDOCT), so that the findings are maintained when collapsed into a two-dimensional fundus image for comparison with conventional retinal studies. SDOCT of the posterior pole of 12 eyes (5 with neovascular age-related macular degeneration [AMD]; 7 with nonneovascular AMD) produced three-dimensional stacks of scans. Location of pathologic features was delineated with color markings in each scan before the stack was collapsed along the depth axis. This en face image contained retinal vessel shadowing and preserved color markings of delineated pathologic features relative to the vessel pattern and was superimposed onto conventional studies. For patients with neovascular AMD, location and extent of choroidal neovascularization, macular edema, and subretinal fluid were visible on the two-dimensional summed images and, in some cases, involved sites not suspected with conventional imaging. For patients with nonneovascular AMD, the location of drusen and geographic atrophy were correlated with autofluorescence images. For one eye with drusen and three eyes with neovascular AMD, presence or extent of subretinal fluid identified by SDOCT was not visible using other imaging methods. In this pilot AMD study, pathologic features within SDOCT scans were transferred into two-dimensional en face projections, enabling researchers to correlate lateral extent of pathologic features from SDOCT with conventional studies. This integration of SDOCT with other retinal studies is promising and will be useful to study the relationship between local OCT morphology and other parameters of retinal disease or function.

To analyze the forces affecting pneumatic displacement of submacular hemorrhage and determine an efficient postoperative positioning method for patients. Geometric analysis of the forces that act upon submacular hemorrhage in the absence and presence of a gas bubble. A component of gravity force of the hemorrhage parallel to the subretinal space is responsible for pneumatic displacement. This component is largest when the patient is looking straightforward and is absent when the patient is positioned facedown. Face down positioning is not optimal for pneumatic displacement of submacular hemorrhage and should be avoided.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are autoimmune demyelinating diseases of distinct etiology presenting with optic neuritis (ON). This study aimed to identify the macular and peripapillary neurovascular alterations that may facilitate the differentiation between NMOSD and MS eyes using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA). A total of 13 NMOSD patients and 40 MS patients were evaluated. After ON, the radial peripapillary capillary (RPC) vessel density was significantly decreased in the superior (S) and inferior (I) sectors in NMOSD compared with MS eyes, whereas in non-ON eyes, the temporal (T) sector of RPC was reduced in MS group. In the ON eyes, the retinal nerve fiber layer in the I and T quadrants was thinner in NMOSD than in MS. Regarding ON and non-ON eyes, the macular capillary plexuses, and the ganglion cell complex thickness did not differ between NMOSD and MS. The ratios, based on the disease-specific intra-eye RPC vessel density reduction pattern, were the best discriminants between NMOSD and MS, i.e., inferior to nasal (I/N) and I/T ratios for ON eyes, and S/T and N/T ratios for non-ON eyes. Our results show that the OCTA-based simple ratios may be useful in distinguishing NMOSD and MS patients.