Robust and Reproducible Generation of Induced Neural Stem Cells from Human Somatic Cells by Defined Factors

Background and Objectives@#Recent studies have described direct reprogramming of mouse and human somatic cells into induced neural stem cells (iNSCs) using various combinations of transcription factors. Although iNSC technology holds a great potential for clinical applications, the low conversion efficiency and limited reproducibility of iNSC generation hinder its further translation into the clinic, strongly suggesting the necessity of highly reproducible method for human iNSCs (hiNSCs). Thus, in orderto develop a highly efficient and reproducible protocol for hiNSC generation, we revisited the reprogramming potentials of previously reported hiNSC reprogramming cocktails by comparing the reprogramming efficiency of distinct factor combinations including ours. @*Methods@#We introduced distinct factor combinations, OSKM (OCT4+SOX2+KLF4+C-MYC), OCT4 alone, SOX2 alone, SOX2+HMGA2, BRN4+SKM+SV40LT (BSKMLT), SKLT, SMLT, and SKMLT and performed comparative analysis of reprogramming potentials of distinct factor combinations in hiNSC generation. @*Results@#Here we show that ectopic expression of five reprogramming factors, BSKMLT leads the robust hiNSC generation (>80 folds enhanced efficiency) from human somatic cells compared with previously described factor combinations. With our combination, we were able to observe hiNSC conversion within 7 days of transduction. Throughout further optimization steps, we found that both BRN4 and KLF4 are not essential for hiNSC conversion. @*Conclusions@#Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

Phialemonium obovatum Keratitis after Penetration Injury of the Cornea

Phialemonium keratitis is a very rare case and we encountered a case of keratitis caused by Phialemonium obovatum (P. obovatum) after penetrating injury to the cornea. This is the first case report in the existing literature. A 54-year-old male was referred to us after a penetration injury, and prompt primary closure was performed. Two weeks after surgery, an epithelial defect and stromal melting were observed near the laceration site. P. obovatum was identified, and then identified again on repeated cultures. Subsequently, Natacin was administered every two hours. Amniotic membrane transplantation was performed due to a persistent epithelial defect and impending corneal perforation. Three weeks after amniotic membrane transplantation, the epithelial defect had completely healed, but the cornea had turned opaque. Six months after amniotic membrane transplantation, visual acuity was light perception only, and corneal thinning and diffuse corneal opacification remained opaque. Six months after amniotic membrane transplantation, visual acuity was light perception only, and corneal thinning and diffuse corneal opacification remained.

A Case of Radiation Retinopathy of Left Eye After Radiation Therapy of Right Brain Metastasis

A 37-year-old female, who had received modified radical mastectomy for cancer of her right breast, presented with decreased visual acuity in the left eye after radiation therapy for the management of the metastasis to her right brain 14 months ago. After ocular examination, we diagnosed her as radiation retinopathy. At the time of the first visit, the corrected best visual acuity was 0.4 in the left eye, and fundus examination revealed cotton wool spots and cystoid macular edema (CME). The findings in the right eye were normal except for cotton wool spots in the superior major arch. Fluorescein angiography (FA) showed marked telangiectasia and microaneurysms in her left eye but tiny microaneurysms in her right eye. Subsequent optical coherent tomography (OCT) showed CME. We injected intravitreal triamcinolone acetonide (TA). Two weeks after treatment, the visual acuity was improved to 0.6 and the retinal thickness was decreased. Three months later, the visual acuity in the left eye was dropped to 0.3 due to the recurrence of CME, so we injected intravitreal TA again. Five months later, visual acuity was improved to 0.5 and OCT revealed the improvement of CME. The incidence of radiation retinopathy is higher in the side nearer to radiation, but careful radiation blocking is also required on the opposite side of irradiation site considering the possibility of radiation retinopathy and careful observation is required on both sides of the eyes when performing fundus examination.

The Clinical Characteristics of Superior Oblique Palsy Associated With Intermittent Exotropia

PURPOSE: The goal of this study was to determine the clinical characteristics of patients with intermittent exotropia (IXT) associated with hypertropia. METHODS: This study recruited 268 hospital patients with IXT associated with hypertropia. After taking history, measuring the angle of deviation, conducting an ocular motor examination, performing a Bielschowsky head tilt test and taking a fundus photograph, the clinical characteristics of 23 patients diagnosed with superior oblique palsy (SOP) were investigated. RESULTS: Twenty-three patients (8.6%) of the 268 subjects with IXT associated with hypertropia were diagnosed with SOP. The average angle of exodeviation was 17.1+/-3.8PD and the angle of hypertropia at primary position was 12.9+/-5.9PD. Excyclotorsion of an eyeball was observed in 19 patients (82.6%), the Bielschowsky head tilt test was positive in all patients, and head tilt or face turn was found in 12 (52.2%) patients. All subjects had inferior oblique overaction, and 20 (86.9%) had superior oblique underaction. Operations to weaken the inferior oblique muscle of the paralytic eye and for horizontal muscles were conducted at the same time. The angle of exodeviation and the angle of hypertropia were, on average, 1.8+/-3.6PD and 2.4+/-2.2PD, respectively, 6 months after the operation. CONCLUSIONS: When patients with intermittent exotropia have hypertropia, the possibility of SOP should be considered. SOP can be detected by determining a history of head tilt and conducting a Bielschowsky head tilt test. Surgical treatment for SOP is advised.