Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells.

Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.

Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy.

PURPOSE: To evaluate the effects of intravitreal bevacizumab pretreatment in vitrectomy with silicone oil infusion for severe diabetic retinopathy. METHODS: Forty-one eyes (39 patients) that underwent primary vitrectomy with silicone oil tamponade for severe diabetic retinopathy were enrolled in this prospective, comparative case-control clinical study. Cases were alternately divided into the following Group 1, intravitreal bevacizumab (1.25 mg) injection 1 week before surgery; or Group 2, no bevacizumab injection. Cases were followed-up for at least 6 months. Postinjection retinal changes, intra- and postoperative findings, and outcomes were compared between groups. RESULTS: Bevacizumab injections induced regression of neovascularization after 1 week. One case developed increased retinal detachment. In Group 1, there were significantly more cases of subretinal bleeding (P < 0.01). The severity of intraoperative and postoperative bleeding was significantly lower in Group 1. The blood reabsorption time was 11.1 +/- 6.3 days in Group 1 and 34.8 +/- 12.0 days in Group 2 (P < 0.01). One case in Group 1 and 2 cases in Group 2 had ultimate retinal detachment. Multiple regression analyses indicated bevacizumab significantly reduced intra- and postoperative bleeding. CONCLUSION: Bevacizumab may reduce intra- and postoperative hemorrhage in diabetic vitrectomy with silicone oil infusion. Increased subretinal bleeding are potential complications.

Nanomedicine-based Curcumin Approach Improved ROS Damage in Best Dystrophy-specific Induced Pluripotent Stem Cells.

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.

Endogenous endophthalmitis with subretinal abscess after dental procedures.

Endogenous endophthalmitis with subretinal abscess is an extremely uncommon complication following dental procedures. An unsuspected source of infection or misdiagnosis of the condition as iridocyclitis may result in inadequate or delayed treatment leading to severe visual impairment. A high index of suspicion is required for accurate diagnosis and prompt treatment. A 49-year-old man was found to have endophthalmitis in his right eye after treatment of gingival abscess. Ophthalmoscopic examination revealed multiple septic emboli and a 4-disc diameter sized subretinal abscess in his retina. No other infectious origin could be found on systemic work-up. Cultures from blood, urine, aqueous and vitreous were all negative. Pars plana vitrectomy was performed 8 days after the initial presentation because of deterioration of visual acuity to finger counting despite intravitreal and systemic antibiotics administration. Visual acuity recovered to 20/25 one month postoperatively and the retina remained attached during follow-up for 1 year. Ophthalmologists should be aware of the possibility of transient septicemia-induced endophthalmitis and subretinal abscess after dental procedures. Prompt intervention with systemic and intravitreal antibiotics combined with pars plana vitrectomy can achieve successful visual and anatomic outcome.

Intravitreal gas injection for macular hole with localized retinal detachment in highly myopic patients.

PURPOSE: This study aimed to evaluate treatment effects of intravitreal gas for macular hole with localized retinal detachment (RD) in highly myopic eyes and to examine how the vitreomacular relationship and other factors may influence treatment outcomes. METHODS: Twenty highly myopic patients with macular holes and localized posterior RD, treated initially with intravitreal injection of C(3) F(8) , were prospectively studied. Recurrent disease was treated with repeated gas injection or vitrectomy according to the extent of detachment. Length of follow-up was ≥ 12 months. Vitreomacular conditions were determined before and within 2 months after gas injection by standard optical coherence tomography. Demographics, refractive errors, axial length, the extent of chorioretinal (CR) atrophy and visual acuity were recorded. RESULTS: The success rate after primary gas injection was 70%. The remaining 30% of patients achieved anatomic success after further treatment, including vitrectomy with gas or silicone oil tamponade and/or scleral buckling. All cases achieved anatomic success after a mean of 1.4 surgeries. Univariate analysis showed that the patterns of the posterior vitreoretinal relationship did not differ significantly between those successfully treated with gas only (group 1) and those requiring vitrectomy (group 2) (p = 1.000). Logistic regression showed no statistically significant differences in any characteristics between groups 1 and 2. CONCLUSIONS: Intravitreal gas tamponade alone may achieve anatomic success in more than two-thirds of highly myopic patients with macular holes and localized RD. Patients with different clinical characteristics and vitreoretinal relationships seem to have similar opportunities to achieve reattachment through this relatively non-invasive surgery.