Purpose: To investigate the effect of a selective aquaporin 4 (AQP4) inhibitor, 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), on the expression of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) production, as well as on the retinal edema in diabetic retina. Methods: Intravitreal injections of bevacizumab, TGN-020, or phosphate-buffered saline (PBS) were performed on streptozotocin-induced diabetic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. Protein levels of VEGF from collected retinas were determined by Western blot analysis. In addition, retinal vascular leakage of Evans Blue was observed in the flat-mounted retina from the diabetic rats in the presence or absence of TGN-020. Volumetric changes of rat retinal Müller cells (TR-MUL5; transgenic rat Müller cells) and intracellular levels of ROS were determined using flow cytometry analysis of ethidium fluorescence in the presence or absence of TGN-020 or bevacizumab under physiological and high glucose conditions. Results: In the diabetic retina, the immunoreactivity and protein levels of VEGF were suppressed by TGN-020. AQP4 immunoreactivity was higher than in the control retinas and the expressions of AQP4 were co-localized with GFAP. Similarly to VEGF, AQP4 and GFAP were also suppressed by TGN-020. In the Evans Blue assay, TGN-020 decreased leakage in the diabetic retinas. In the cultured Müller cells, the increase in cell volumes and intracellular ROS production under high glucose condition were suppressed by exposure to TGN-020 as much as by exposure to bevacizumab. Conclusion: TGN-020 may have an inhibitory effect on diabetic retinal edema.

We previously reported on the elevated intravitreal activities of tryptase and chymase in association with idiopathic epiretinal membrane (ERM) and idiopathic macular hole (MH). In this present study, we investigated the potential intraocular production of these serine proteases, and measured and compared tryptase and chymase activities in the vitreous body and serum in ERM, MH, proliferative diabetic retinopathy (PDR), and rhegmatogenous retinal detachment (RRD) patients. In addition, nuclear staining with hematoxylin and eosin (H&E) and mast-cell staining with toluidine blue were performed on samples of the vitreous core and bursa premacularis (BPM) of MH. We also performed immunostaining on the above two regions of vitreous samples for MH with anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) antibody, and anti-fibroblast antibody. Moreover, we performed immunostaining with anti-tryptase antibody and anti-chymase antibody on ERMs collected intraoperatively. Tryptase activity in the vitreous body was significantly higher in ERM and MH than in PDR. However, no significant differences were observed in the tryptase activity in the serum among these four diseases. Chymase activity in the vitreous body was significantly higher in MH than in the other three diseases, yet chymase activity in the serum was below detection limit in any of the diseases. Nuclear staining with H&E revealed an abundance of nuclei in the BPM region, but few in the surrounding area. Mast-cell staining with toluidine blue revealed that the BPM showed metachromatic staining. In immunostaining with anti-fibroblasts antibody, anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, and anti-LYVE-1 antibody, the BPM stained more strongly than the vitreous core. Tryptase and chymase-positive cells were also observed in ERM. These findings revealed that the presence of mast cells in the BPM potentially represent the source of these serine proteases. Moreover, the BPM, as a lymphatic tissue, may play an important role in the pathogenesis of macular disease.

These results indicate that RGC-5 cells become susceptible to SNAP under hypoxic conditions in which NO may have greater impact on mitochondrial function.

Purpose: To report a case of large sarcoid choroidal granuloma that was successfully treated with steroid pulse therapy. Case Report: A 38-year-old man presented with the primary complaint of decreased visual acuity (VA) in his left eye. Upon examination, a large white protruding lesion of 10 × 8 papilla diameter in size was observed in the macular region, and slightly temporal to it, in the patient's left eye. Whole-body contrast-enhanced computed tomography performed for differential diagnosis detected numerous enlarged lymph nodes throughout the body, including the bilateral hilar regions. Sarcoidosis was diagnosed by biopsy of the right cervical lymph nodes showing noncaseating epithelioid cell granuloma. The fundus lesion was found to be a choroidal granuloma caused by sarcoidosis, and steroid pulse therapy was started. The granuloma was considerably decreased, and the VA in the left eye improved to 0.7 after 2 months. Conclusion: Steroid pulse therapy was found to be effective as an initial treatment for a large sarcoid choroidal granuloma.

<b><i>Purpose:</i></b> We investigated the thinning of central choroidal thickness (CCT) following intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs to treat central retinal vein occlusion (CRVO)-related macular edema in patients with and without systemic hypertension (HT) to assess the influence of repeated anti-VEGF therapy and HT on the choroid in CRVO eyes. <b><i>Methods:</i></b> We conducted a retrospective study involving 27 patients with CRVO-related macular edema from January 2014 to July 2017, with follow-ups exceeding 18 months. Visual acuity (VA), central retinal thickness (CRT), and CCT were evaluated before and after initial anti-VEGF drug treatment during follow-up. <b><i>Results:</i></b> The mean follow-up period was 35.2 months. Seventeen (63.0%) patients had HT. At 1 month after treatment, VA had improved in 21 (77.8%) patients, and CRT had decreased in 25 (92.6%). At the final visit, 22 (81.5%) showed improved VA, 19 (70.4%) had resolved macular edema, and the CCT had gradually become thinner with additional drug injections in all the patients. Furthermore, the mean CCT in HT patients (209.0 µm) was significantly lower than in non-HT patients (256.1 µm), and the mean injections were 7.8 and 5.3, respectively (<i>p</i> = 0.2067). <b><i>Conclusion:</i></b> The CCTs were thinner in eyes with HT than in eyes without HT both before and after the repeated anti-VEGF injections.

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger’s space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.

Purpose: We investigate seasonal variations found in patients with central serous chorioretinopathy (CSC). Methods: We retrospectively investigated 201 CSC patients at the Osaka Medical College Hospital from January 2011 to December 2016 and evaluated their seasonal and monthly distributions. Results: The study population comprised 149 males and 52 females. There were significant seasonal differences in the distribution of patients, with 62 cases in spring, 37 in summer, 59 in autumn, and 43 in winter, and the monthly prevalence of CSC was high in March (n = 24), April (n = 22), and November (n = 23). In addition, seasonal variation of serous retinal detachment (SRD) in the macula could be observed in 12 recurrent CSC cases. Conclusions: The prevalence of CSC development was the highest in spring. In addition, recurrent SRD in the macula showed seasonal variation in some CSC patients. As factors related to CSC, season and temperature might influence the pathophysiology of CSC.

The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases. No statistically significant age differences existed among the groups. Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM: 6.67±4.04/18.82±7.10, MH: 10.3±7.02/17.00±4.8, PDR: 4.2±3.05/15.83±3.46, and RD: 10.00±4.58/16.06±4.57, while those in serum were ERM: 31.67±5.51/5.82±1.08, MH: 21.00±8.89/7.53±3.2, PDR: 29.20±7.07/12.75±10.62, and RD: 24.33±6.51/7.5±4.42. E2 concentrations were significantly higher (P<0.001) in the male serum than vitreous, yet significantly higher in the female vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female vitreous were ERM: 0.15±0.03/0.15±0.01, MH: 0.15±0.01/0.15±0.01, PDR: 0.15±0.03/0.16±0.12, and RD: 0.14±0.01/0.17±0.08, while those in serum were ERM: 4.54±1.46/0.16±0.01, MH: 8.04±2.29/0.16±0.10, PDR: 5.14±1.54/0.22±0.11, and RD: 3.24±0.75/0.17±0.10. T concentrations were high in the male serum, yet extremely low in the male and female vitreous and female serum. High concentrations of E2 were found in the vitreous, and women, in particular, exhibited significantly higher concentrations in the vitreous than in the serum. This finding suggests the possibility that in vitreoretinal disease cases, the synthesis of E2 is increased locally only in female eyes.