The range of IOP fluctuation was larger in the eyes with NTG than in the nonglaucoma eyes. This larger fluctuation might be one of the reasons underlying the aggravation of the visual field by NTG. Measurements of 24-hour continuous IOP might be one of the useful methods to distinguish NTG from nonglaucoma eyes.

Purpose. To evaluate the efficacy of setting a preferred retinal locus relocation target (PRT) and performing Macular Integrity Assessment (MAIA) biofeedback training in patients showing insufficient recovery of best corrected visual acuity (BCVA) despite successful closure of an idiopathic macular hole (MH). Methods. Retrospective interventional case series. Nine eyes of 9 consecutive patients with the decimal BCVA of less than 0.6 at more than 3 months after successful MH surgery were included. A PRT was chosen based on MAIA microperimetry and the patients underwent MAIA biofeedback training. BCVA, reading speed, fixation stability, and 63% bivariate contour ellipse area (BCEA) were evaluated before and after the training. Statistical analysis was carried out using paired Student's t-test. Results. PRT was chosen on the nasal side of the closed MH fovea in 8 patients. After the MAIA training, BCVA improved in all patients. The mean logMAR value of BCVA significantly improved from 0.33 to 0.12 (p = 0.007). Reading speed improved in all patients (p = 0.29), fixation stability improved in 5 patients (p = 0.70), and 63% BCEA improved in 7 patients (p = 0.21), although these improvements were not statistically significant. Conclusion. MAIA biofeedback training improved visual acuity in patients with insufficient recovery of BCVA after successful MH surgery.

Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation.

Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protein kinase (ROCK), the downstream kinase of Rho. We herein investigated the effect of Y-27632 in vitro on retinal pigment epithelium derived from induced pluripotent stem cells (iPS-RPE cells), and also its effects in vivo on the transplantation of iPS-RPE cell suspensions. As a result, the addition of Y-27632 in vitro showed suppression of apoptosis, promotion of cell adhesion, and higher proliferation and pigmentation of iPS-RPE cells. Y-27632 also increased the viability of the transplant without showing obvious retinal toxicity in human iPS-RPE transplantation into monkey subretinal space in vivo. Therefore, it is possible that ROCK inhibitors can improve the engraftment of iPS-RPE cell suspensions after transplantation.

No abstract

Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4+ T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions.

Diethyl 5‐isopropenyl‐4,5‐dihydrofuran‐2,3‐dicarboxylate 1a and methyl 5‐isopropenyl‐3‐methoxy‐carbonyl‐4,5‐dihydrofuran‐2‐acetate 2a were prepared by cylization of diethyl 2‐oxosuccinate or dimethyl 3‐oxoglutarate with (E)‐1,4‐dibromo‐2‐methyl‐2‐butene. Their chemical properties were studied.

REVS using a specially made micro-needle may be a surgical treatment option for non-ischemic CRVO, but it did not seem effective for ischemic CRVO.