記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate the time courses of morphologic changes in the transplanted grafts, including the retinal layer, the ellipsoid zone (EZ) and the visual acuity (VA) after autologous retinal transplantation (ART) in patients with primary large macular holes (MHs). DESIGN: Single-center, retrospective cohort study. SUBJECTS: The study included 17 eyes of 17 patients who had undergone ART. All patients fulfilled the following criteria: (1) MH was the only disease-causing anatomic abnormality of the macula; (2) they could be followed up for at least 12 months after ART surgery; (3) they had no other systemic disorders; and (4) the MH was > 400 μm in diameter. METHODS: Data of all patients who underwent assessment of the VA and spectral-domain (SD)-OCT at 1, 3, 6, and 12 months after surgery were analyzed. The morphologic features of the graft and the EZ were measured by SD-OCT. MAIN OUTCOME MEASURES: Changes in the morphologic features of the graft (graft thickness, overall graft area, graft length, area of outer retina, and EZ) and VA over 1 year after surgery. RESULTS: Closure of the MH was achieved in all patients. The VA was 0.59 ± 0.27 (logarithm of the minimal angle of resolution units) at 1-year postsurgery compared with 0.84 ± 0.22 before surgery (P < 0.05). The retinal layers gradually became smoothly connected. Although a decrease in graft thickness and overall graft area was observed, the length and area of the outer retina were maintained throughout the follow-up period. The presence of the EZ was observed in 9 patients (52.9%) and our analyses revealed significantly greater improvement of VA in these patients than in those without the EZ (P < 0.05). Moreover, the incidence of macular edema (ME) was higher in the group without the EZ (P = 0.04; chi-square test). CONCLUSION: Patients showed significant improvements of the VA. Morphologically, the layers were gradually connected to each other, and the outer retina was particularly maintained. Especially, patients in whom an EZ was restored in the graft showed a low prevalence of ME and greater improvement of the VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

DOI： 10.1016/j.oret.2022.12.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anastomosis on graft retina was studied after autologous retinal transplantation (ART) on 26 eyes with primary and refractory macular holes. Angiogenesis and anastomosis were seen in 35% of the eyes with successful ART, likely contributing to the survival of the transplanted retina.

DOI： 10.1016/j.oret.2022.05.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To examine the usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO). METHODS: Ultra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group. RESULTS: No significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026). CONCLUSIONS: UWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

DOI： 10.1371/journal.pone.0260383

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Retinal pigment epithelium (RPE) cells is the outermost layer of the retina and RPE dysfunction is a key factor in the disease pathogenesis of age-related macular degeneration (AMD). Transplantation therapy using induced pluripotent stem cell (iPSC)-derived RPEs has recently received much attention as a treatment for AMD. Preserving these cells under the best possible conditions is important, and preservation methods using Y-27632 have been reported. Rho-associated coiled-coil containing kinase (ROCK) inhibitors are known to inhibit cell death, emerging as important drug candidates for stem cell differentiation and regenerative medicine. However, it has recently been shown that ROCK inhibitors may have a vasodilatory effect on human retinal arterioles, a side effect that should ideally be avoided in RPE transplantation. Although ROCK inhibitors hold great potential, optimizing efficacy while minimizing adverse reactions is critical for translation into a clinical treatment. We examined the effect of transient exposure of RPE cells to ROCK inhibitor Y-27632 to determine whether the extracellular presence of the drug is necessary for ongoing Rho/ROCK downregulation. Human RPE cells were subcultured as a suspension for 4 h in drug-free medium following exposure to Y-27632 for 2 h. A Y-27632 concentration of >10 μM improved cell survival beyond 4 h and cell proliferation in recovery culture medium. ROCK2 expression levels were specifically downregulated by Y-27632 in the Rho/ROCK signaling pathway. In conclusion, we demonstrated that the effect of Y-27632 is not dependent on its extracellular availability and can last beyond the 2 h of exposure. The lasting Rho/ROCK signaling pathway downregulation by Y-27632 suggests that RPE cell transplantation with ROCK inhibitor-free media is possible, which can minimize side effects to host tissue and have wider implications for transplantation methods requiring ROCK inhibition.

DOI： 10.1016/j.bbrep.2020.100841

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s40123-019-00207-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (hiPSC-RPE) cells suspension have the potential for regenerative treatment. However, practical regenerative applications with hiPSC-RPE cells require the development of simple and cost-effective non-freezing preservation methods. We investigated the effect of non-freezing temperatures on suspended hiPSC-RPE cells in various conditions and analysed mechanisms of cell death, anoikis, Rho GTPases, hypoxia, microtubule destruction, and cell metabolism. Cells stored at 37 °C had the lowest viability due to hypoxia from high cell metabolism and cell deposits, and cells preserved at 4 °C were damaged via microtubule fragility. Cell suspensions at 16 °C were optimal with drastically reduced apoptosis and negligible necrosis. Moreover, surviving cells proliferated and secreted key proteins normally, compared to cells without preservation. hiPSC-RPE cell suspensions were optimally preserved at 16 °C. Temperatures above or below the optimal temperature decreased cell viability significantly yet differentially by mechanisms of cell death, cellular metabolism, microtubule destruction, and oxygen tension, all relevant to cell conditions. Surviving cells are expected to function as grafts where high cell death is often reported. This study provides new insight into various non-freezing temperature effects on hiPSC-RPE cells that are highly relevant to clinical applications and may improve cooperation between laboratories and hospitals.

DOI： 10.1038/s41598-018-38065-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We investigated the efficacy of additional topical betamethasone in persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors (CAIs) therapy. METHODS AND ANALYSIS: This retrospective cohort study included 16 eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously administered CAI for at least 3 months to treat CMO secondary to RP and lacking an effective reduction (≥11%) of central foveal thickness (CFT). We administered topical 0.1% betamethasone daily in each affected eye following a preceding course of the CAI medication as a first treatment. CMO was diagnosed using spectral-domain optical coherence tomography. CFT was regarded as the average of vertical and horizontal foveal thickness. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained from patient medical records. We compared the CFT and BCVA between baseline and the average of 1-3, 5-7, 10-14 and 16-20 months period. RESULTS: In treatments with brinzolamide in 14 eyes, dorzolamide in 2 eyes and bromfenac in 2 eyes, CFT effectively decreased in 12 of 16 eyes (81%). CFT decreased significantly in 1-3 months (326±102 µm; n=16; P=0.029) and 5-7 months (297±102 µm; n=12; P=0.022) compared with baseline but not within 10-14 months (271±96 µm; n=9; P=0.485) or 16-20 months (281±134 µm; n=9; P=0.289). There were no significant intergroup differences in BCVA throughout the study. Betamethasone treatment was stopped in three patients because of IOP elevation. CONCLUSION: Our data suggested that additional betamethasone might improve treatments for persistent CMO. Topical steroids could be an alternative option for managing persistent CMO in RP.

DOI： 10.1136/bmjophth-2017-000107

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