SummaryIncreasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets.

PurposeThe purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP).Patients and methodsThis was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum angle of resolution (logMAR) ranged from 1.0 to 0.16 with visual fields (VFs) of ≤10° (measured using Goldmann perimeter with I4) were recruited. The patients received oral supplementation with 400 mg of VPA daily for 6 months and were followed for an additional 6 months. BCVAs, VFs (measured with the Humphrey field analyzer central 10-2 program), and subjective questionnaires were examined before, during, and after the cessation of VPA supplementation.ResultsThe changes in BCVA and VF showed statistically significant differences during the internal use of VPA, compared with after cessation (P=0.001). With VPA intake, BCVA in logMAR significantly improved from baseline to 6 months (P=0.006). The mean deviation value of the VF significantly improved from baseline to 1 month (P=0.001), 3 months (P=0.004), and 6 months (P=0.004). These efficacies, however, were reversed to the baseline levels after the cessation of VPA intake. There were no significant relations between the mean blood VPA concentrations of each patient and the changes in BCVA and VF. During the internal use of VPA, 15 of 29 patients answered “easier to see”, whereas blurred vision was registered in 21 of 29 patients on cessation. No systemic drug-related adverse events were observed.ConclusionWhile in use, oral intake of VPA indicated a short-term benefit to patients with RP. It is necessary to examine the effect of a longer VPA supplementation in a controlled study design.

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Background Neurotrophic keratopathy (NK) is a rare degenerative corneal disease caused by damage to the trigeminal nerve. We hereby describe a severe case with bilateral corneal perforation due to leprosy (Hansen’s disease)-associated NK. Case presentation An 89-year-old man with a history of leprosy treated 40 years previously in our sanatorium developed bilateral corneal perforation due to NK. He had a history of bilateral persistent epithelial defects and bacterial keratitis. Although epithelialization was obtained with the use of autologous serum eye drops, progressive corneal thinning concomitant with stromalysis led to bilateral perforation. Over one month treatment with topical antibiotics, anti-inflammatory and lubricants resulted in healing of the epithelial defects and corneal perforations. A Cochet-Bonnet esthesiometer demonstrated a total absence of corneal sensation in both eyes. Conclusions The present case indicated the irreversible nerve damage due to leprosy that had been cured 23 years ago, which can progress over the years and cause bilateral corneal perforations.