Diabetic retinopathy (DR) is an inflammatory and progressive vaso-occlusive disease resulting in angiogenesis. Galectin-1 is a hypoxia-induced angiogenic factor associated with cancer and proliferative DR. Here we reveal a significant upregulation of galectin-1 in eyes of DR patients along with progression of clinical stages beginning from the pre-ischemic, inflammatory stage with diabetic macular edema, but not in eyes with non-diabetic retinal vascular occlusions. As for its regulatory mechanism unrelated to hypoxia but selective to DR, in vitro galectin-1/LGALS1 expression was shown to increase after application to Müller glial cells with interleukin (IL)-1β, which was induced in monocyte-derived macrophages and microglial cells via toll-like receptor (TLR) 4 signaling stimulated by advanced glycation endproducts (AGE). In vivo inhibition of AGE generation with aminoguanidine, macrophage depletion with clodronate liposomes, and antibody-based blockade of Il-1β and Tlr4 attenuated diabetes-induced retinal Lgals1 expression in mice. Fibrovascular tissues from proliferative DR eyes were immunoreactive for AGE, TRL4 and IL-1β in macrophages, and IL-1β receptor-positive glial cells expressed galectin-1. Therefore, diabetes-induced retinal AGE accumulation was suggested to activate IL-1β-related inflammatory cues in macrophages followed by Müller cells, linking to galectin-1 upregulation in human DR with time. Our data highlight AGE-triggered inflammation as the DR-selective inducer of galectin-1.

The current data demonstrated the presence of FDP-Lys in fibrovascular tissues and indicate its involvement in fibrovascular proliferation in PDR.

Our results indicate the pathological role of sVAP-1/SSAO to generate hydrogen peroxide and toxic aldehyde ACR, both of which are associated with oxidative stress, as a consequence of spermine oxidation in eyes with PDR.

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP). Three-week-old GLAST+/− mice were given oral administration of GGA at 100, 300, or 600 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. At 5 weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. In addition, retrograde labeling technique was also used to quantify the number of RGC. Expression and localization of heat shock protein 70 (HSP70) in retinas were evaluated by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Activities of caspase-9 and -3 in retinas were also assessed. The number of RGCs of GLAST+/− mice significantly decreased, as compared to that of control mice. RGC loss was significantly suppressed by administration of GGA at 600 mg/kg/day, compared with vehicle alone. Following GGA administration, HSP70 was significantly upregulated together with reduction in the activities of caspase-9 and -3. Our studies highlight HSP70 induction in the retina is available to suppress RGC degeneration, and thus GGA may be applicable for NTG as a promising therapy.

Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively. Administration of prorenin to Müller glial cells enhanced mRNA expression of fibroblast growth factor 2, while Ang II application stimulated the expression of glial cell line-derived neurotrophic factor, nerve growth factor, and transforming growth factor-β1. These expression levels induced by prorenin or Ang II were reversed by (P)RR or AT1R blockade, respectively. Immunofluorescence revealed tissue co-localization of (P)RR and AT1R with the products of the upregulated genes in vitro. The present findings suggest the involvement of RAPS in the pathogenesis of iERM.

Phosphorylation of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

This study demonstrated increased VEGF expression in human conjunctival and orbital EMZL compared with that in RLH, suggesting that VEGF plays a significant role in the pathogenesis and tumor angiogenesis of ocular adnexal lymphoma.

Background/Aim: Orbital solitary fibrous tumor (SFT) is a rare lesion among orbital tumors, which can be misdiagnosed as another mesenchymal tumor. In this study we report two cases of orbital SFT, focusing on the imaging and pathological findings of the vascular structure inside the tumor. Case Report: A 26-year-old woman and 43-year-old man presented with orbital SFT. The pathological findings revealed a patternless growth pattern of the tumor cells and hemangiopericytoma-like vascularity as well as thickened, dilated blood vessels within the tumor tissue. Tumor cells revealed a diffuse strong positivity for cluster of differentiation 34 (CD34) and signal transducer and activator of transcription 6 (STAT6) in both cases, while Bcell lymphoma 2 (bcl-2) and CD99 were positive in one case. Characteristic findings within the tumor were the arterial components, where a variety of STAT6, CD99 and bcl-2positive smooth muscle cells were intermingled. Conclusion: Histologically, the tumor tissues might be characterized by not only conventional hemangiopericytoma-like vasculature but also dilated arterial vessels, which were shown to be part of the tumor components.Solitary fibrous tumor (SFT), a rare spindle-cell tumor, commonly arises from the pleura (1) but may also occur in extrapleural sites (2-5). Orbital SFT is a rare lesion and about 90 cases have been reported in the literature to date (6, 7). This tumor is likely to simulate other mesenchymal tumors such as fibrous histiocytoma, liposarcoma, synovial sarcoma, and neurofibroma. Since SFT is rich in feeding arteries, preoperative clinical diagnosis is important in assessing the likelihood of intraoperative bleeding (8), and total tumor resection is recommended (9). However, histopathological findings of the feeding vessels in SFT remain unknown. In this study, we report two cases of orbital SFT, focusing on the imaging and pathological findings of the vascular structure inside the tumor. The institutional review board in Hokkaido University and Teine Keijinkai Hospital waived the ethical assessment of the clinical study because of case reports. This study adhered to the principles of the Declaration of Helsinki. Case ReportCase 1. A 26-year-old woman presented with progressive and painless lower eyelid swelling for 2 months. An elastic hard, non-tender and non-pulsatile mass was palpable in the lower eyelid. Computed tomography revealed a well-defined heterogeneous mass along the lower wall of the right orbit (Figure 1A). Magnetic resonance imaging (MRI) demonstrated an orbital lesion with an isointense signal on T1-weighted images (T1WI) (Figure 1B) and a hyperintense signal on T2weighted images (T2WI) (Figure 1C). Postcontrast T1WI revealed a strong enhancement of the lesion that contained a linear flow void-like hypointensity (Figure 1D, arrow). Surgical excision was performed. There was bleeding from the 3649 This article is freely accessible online.