Supplementary Material for: Retinal Endovascular Surgery with Tissue Plasminogen Activator Injection for Central Retinal Artery Occlusion

<b><i>Purpose:</i></b> To report 2 cases of central retinal artery occlusion (CRAO) who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA) into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. <b><i>Methods:</i></b> Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL) solution was injected into the retinal artery of the optic disc for 2–3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT), fluorescein angiography, and laser speckle flowgraphy (LSFG) results were examined. <b><i>Results:</i></b> Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. <b><i>Conclusions:</i></b> Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO

Supplementary Material for: Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

<i>Background/Aims:</i> De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice). <i>Methods:</i> As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application. <i>Results:</i>After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of <i>Lotus tetragonolobus</i> lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74. <i>Conclusion:</i> Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression

Supplementary Material for: Heart Failure Complicated by Alveolar Hemorrhage due to Vascular Collapse and Amyloid Deposits in Wild-Type Transthyretin Amyloidosis

<p>The main clinical manifestations of wild-type transthyretin (TTR)-related amyloidosis are progressive heart failure and neuropathy. There have been some reports on cerebral hemorrhage due to cerebral amyloid angiopathy in patients with TTR-related amyloidosis, but little is known about the vascular involvement in other organs. A 77-year-old woman experienced heart failure and was admitted for deteriorating heart failure status. Echocardiography showed diffuse hypokinesis of the left ventricle with biventricular wall thickness. On the 12th hospital day, the blood oxygen saturation level suddenly dropped and, despite oxygen supplementation and intensive care, the patient died. An autopsy revealed systemic deposition of amyloids which were immunolabeled by an anti-TTR antibody. Furthermore, gene-sequencing analysis showed no evidence of TTR gene mutations. The patient was diagnosed postmortem with wild-type TTR-related amyloidosis. Pathological findings revealed alveolar hemorrhage of the lung. Massive amyloid deposits were present in the vessels, and collapsed internal elastic laminae with lymphocyte infiltration were observed at the site of amyloid deposits in the bronchial artery, suggesting that deposits with inflammation might cause the collapse of the bronchial artery and lead to hemorrhage. In amyloidosis patients who suffer heart failure, there is the potential for vascular collapse caused by the accumulation of amyloid deposits with inflammation.</p