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Human pluripotent stem cells (hPSCs), which include induced pluripotent stem cells and embryonic stem cells, are powerful tools for studying human development, physiology and disease, including those affecting the retina. Cells from selected individuals, or specific genetic backgrounds, can be differentiated into distinct cell types allowing the modelling of diseases in a dish for therapeutic development. hPSC‐derived retinal cultures have already been used to successfully model retinal pigment epithelium (RPE) degeneration for various retinal diseases including monogenic conditions and complex disease such as age‐related macular degeneration. Here, we will review the current knowledge gained in understanding the molecular events involved in retinal disease using hPSC‐derived retinal models, in particular RPE models. We will provide examples of various conditions to illustrate the scope of applications associated with the use of hPSC‐derived RPE models. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle-chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or ?-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans. [ABSTRACT FROM AUTHOR]

The enantioselective iodolactonizations of a series of diversely substituted olefinic carboxylic acids are promoted by a BINOL-derived, bifunctional catalyst. Reactions involving 5-alkyl- and 5-aryl-4(Z)-pentenoic acids and 6-alkyl- and 6-aryl-5(Z)-hexenoic acids provide the corresponding γ- and δ-lactones having stereogenic C–I bonds in excellent yields and >97:3 er. Significantly, this represents the first organocatalyst that promotes both bromo- and iodolactonization with high enantioselectivities. The potential of this catalyst to induce kinetic resolutions of racemic unsaturated acids is also demonstrated. [ABSTRACT FROM AUTHOR]

A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactomzations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl- substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon-bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization. [ABSTRACT FROM AUTHOR]

A catalytic, highly diastereoselective process for the synthesis of trans-β-lactams is reported. This system is based on a phosphonium fluoride precatalyst that both activates the nucleophile and directs the reaction process for high yield and diastereo�selectivity. [ABSTRACT FROM AUTHOR]

We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, α-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph[sub3]P)[sub2]PdCl[sub2] was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base! Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

Triclocarban (TCC) and triclosan (TCS) are antimicrobial additives in personal care products. Whereas TCS has been studied extensively, the environmental fate of TCC remains largely unknown. To address this data gap, we performed quantitative structure-activity relationship (USAR) analyses that suggested a propensity of ICC to persist in various environmental compartments with predicted half-lives ranging from 0.75 days in air to 540 days in sediment Moreover, concentrations of both antimicrobials were measured in 42 environmental samples from the Greater Baltimore region using a combination of solid-phase extraction, liquid chromatography/mass spectrometry, and isotope dilution. The co-occurrence of TCC and TCS was observed, owing to similar properties, usage, disposal, and environmental half-lives. A linear empirical correlation (R2 = 0.9882) fit the log-log-transformed data from diverse aquatic media and spanned 5 orders of magnitude in concentration. Occurrences of TCC predicted for 85 U.S. streams were statistically indistinguishable from experimental regional data (α &les; 0.05). Annual loading of antimicrobials to water resources probably is dominated by activated sludge treatment plants (39-67%), followed by trickling filters (31 -54%) and combined and sanitary sewer overflows (2-7% and <0.2%, respectively). Study results suggest that ICC is a previously unrecognized contaminant of U.S. water resources nationwide, likely ranking in the top 10 in occurrence rate and in the top 20 in maximum concentration among 96 organic pollutants considered. The magnitude and frequency of TCC contamination (regional, 6750 ng/L, 68%; predicted nationwide for 1999-2000, 1150 ng/L, 60%) were markedly higher than non-peer- reviewed numbers (240 ng/L, 30%, U.S.) currently used by the U.S. Environmental Protection Agency for evaluating TCC's ecological and human health risks. [ABSTRACT FROM AUTHOR]

Triclocarban, N-(4-chlorophenyl)-W-(3,4-dichlorophenyl) urea, is a polychlorinated phenyl urea pesticide, marketed under the trademark TCC and used primarily as an antibacterial additive in personal care products. Despite its extensive use over several decades, environmental occurrence data on ICC are scarce. This is due in part to a lack of analytical techniques offering the desired sensitivity, selectivity, affordability, and ease of use. This need is addressed here by introducing a liquid chromatography electrospray ionization mass spectrometry (LC/ESI/MS) method allowing for the determination of TCC concentrations in aquatic environments at the ng/L level. ICC was concentrated from aqueous samples by solid-phase extraction, separated from interferences on a C18 column by either isocratic or gradient elution, and detected and identified in negative ESI mode by selectively monitoring the (M - H)- base peak (m/z313) and its 37Cl-containing isotopes (m/z 315, 317) that served as reference ions. Particulates contained in aquatic samples were extracted and analyzed separately. Accurate quantification was achieved using stable isotopes of ICC and triclosan as internal standards. Addition of 10 mM acetic acid to the mobile phase yielded acetic acid adducts (EM - H + 60]-) that were successfully exploited to boost method sensitivity and selectivity, especially when analyzing challenging environmental matrixes. Method detection limits were matrix dependent, ranging from 3 to 50 ng/L. In 36 grab samples obtained from the Greater Baltimore area, ICC was detected in river water and wastewater at concentrations of up to 5600 and 6750 ng/L, respectively. Raw and finished drinking water did not contain detectable quantities of the pesticide (<3 ng/L). In conclusion, the new LC/ESl/ MS method was applied successfully to collect environmental occurrence data on ICC in U.S. water resources. Study results suggest that the bacteriostat and pesticide is a frequent but currently underreported contaminant whose environmental fate and behavior deserve further scrutiny. [ABSTRACT FROM AUTHOR]

Background: Most coronary artery bypass grafting (CABG) operations still involve the use of greater saphenous vein (GSV) for one or more grafts, even with the increasing use of arterial conduits for coronary revascularization. Wound complications from GSV harvesting are common, and sometimes severe. In order to reduce the morbidity of this procedure, we adopted a technique of endoscopic vein harvesting (EVH). EVH allows nearly complete harvest of the GSV, with excellent visualization, through minimal incisions. At our institution, a physician’s assistant routinely performs EVH, usually while a cardiothoracic surgeon harvests an arterial conduit. In 1997, all GSV harvesting was performed by open technique. During a transition period in 1998 and 1999 we used several different endoscopic techniques. By the beginning of 2000, our technique of EVH was standardized and used routinely.Methods: To determine whether EVH reduced the morbidity associated with conventional open vein harvesting (OVH), we reviewed the charts of all patients having primary coronary artery bypass operations utilizing GSV during the years 1997 and 2000.Results: The two groups were comparable in risk factors for leg incision complications. The year 2000 EVH group had a marked reduction in the number of wound complications compared with the year 1997 OVH group (7.1% versus 26.1%, P < 0.00001). There were no significant differences between the two groups in total operative time (OVH 224 minutes, EVH 223 minutes, number of distal coronary anastomoses (OVH 3.38 ± 0.90, EVH 3.38 ± 0.94), or the rate of clinically apparent early graft failure. There was a significant increase in the use of sequential grafting techniques in the 2000 group (OVH 21.9%, EVH 43.6%, P < 0.00001).Conclusions: EVH reduced the morbidity associated with GSV harvesting. EVH was associated with an increased use of sequential coronary grafting techniques. EVH does not prolong operative time when performed by experienced personnel. We believe EVH should become the standard of care. [Copyright &y& Elsevier]

A catalytic, asymmetric process for the synthesis of 1,4-benzoxazinones from o-benzoquinone imides and ketene enolates is reported. Addition of Lewis acids (Zn(OTt)2, In(OTf)3, and in particular Sc(OTf)3) creates a bifunctional catalytic system that dramatically increases the reaction rate and the yield of these non-natural amino acid precursors while preserving the remarkable enantioselectivity inherent to the reaction. Cocatalyst Sc(OTf)3 increases the yield by up to 42% while producing products in >99% ee. [ABSTRACT FROM AUTHOR]

The article discusses the catalytic, asymmetric α-fluorination of acid chlorides and dual metal— ketene enolate activation. It states that a catalytic highly enantioselective α-fluorination of acid chlorides exploits dual activation strategy. It mentions that dual activation is demonstrated in the broad range of different derivatives that can be synthesized depending on the work up conditions including fluorinated carboxylic acids, amides, esters and peptides.

The authors demonstrate a highly enantioselective bifunctional catalyst system for the cycloaddition of quinoxalinones from o-benzoquinone diimides and acid chlorides. In the course of their study, they tested the hypothesis that the Lewis acid cocatalysts increase the electrophilicity of the diimide without interfering with the nucleophilic enolate. They claim that the cycloadducts will serve well as scaffolds for drug development and as synthetic intermediates.

Presents a letter to the editor in response to an article on the co-occurrence of Triclocarbon and Triclosan in the U.S. water resources.

A bifunctional BINAP-derived amidine is shown to be highly efficient for the process. [ABSTRACT FROM AUTHOR]

The nouvel bifunctional BINOL derived title catalyst promotes, like some other known catalysts, not only the highly enantioselective bromolactonization of 4- and 5-arylpentenoic acids (III) and (V), but it also catalyzes the bromolactonization of 5-alkyl-4(Z)-pentenoic acids (I) via 5-exo mode cyclizations. [ABSTRACT FROM AUTHOR]

Abstract: A formal synthesis of didehydrostemofoline and isodidehydrostemofoline has been accomplished by preparing an intermediate in the Overman synthesis of these alkaloids from commercially available 2-deoxy-d-ribose. The work presented in this account chronicles the evolution of our explorations to identify the optimal steric and electronic control elements necessary to generate the tricyclic core structure of these alkaloids in a single operation from an acyclic precursor. The key step in the synthesis is a novel dipolar cycloaddition cascade sequence that is initiated by cyclization of a rhodium-derived carbene onto the nitrogen atom of a proximal imine group to generate an azomethine ylide that then undergoes spontaneous cyclization via dipolar cycloaddition. The synthesis features several other interesting reactions, including a Boord elimination to prepare a chiral allylic alcohol, a highly diastereoselective Hirama–Itô cyclization, and a useful modification of the Barton decarboxylation protocol. [Copyright &y& Elsevier]

Genetic studies of PTSD are complicated by the complex interplay between environmental traumatic exposures and genetics. To understand how genomic risk loci functionally mediate disorder risk, it is important to explore the regulatory activity of such loci in disorder-associated cell types and contexts. Here, we utilize hiPSC-derived neuronal models to develop a controlled model of stress exposure. Our previous work has identified a PTSD diagnosis-dependent gene expression signature in hiPSC-derived neurons to hydrocortisone (HCort). We have also demonstrated that common genetic variation impacts stress response in the post-mortem brain. Here, we integrate both signatures to show how common genetic variants may mediate differential response to stress in a cell type- and tissue-specific manner. In 304 post-mortem brains, we modeled a linear eQTL association using an interaction term between trauma exposure and genotype across four brain regions. To validate our signatures in vitro, we generated GABAergic and glutamatergic neurons from combat-exposed veterans with PTSD (n=20) and without (n=20), and treated neurons with HCort. We performed interactive-eQTL associations on HCort-treated neurons. Identified eQTLs were functionally fine-mapped by cell type deconvolution, integration with CHIP-seq datasets, and gene set enrichment of disorder-related genes. We identified 915 trauma-interactive eGenes across 4 post mortem brain regions. Up to 61% of interactive-eGenes replicated in HCort-treated neurons. eGenes enrich in previously reported post-mortem PTSD signatures, as well as psychiatric GWAS catalog genes. eQTLs show varying strengths and directions of effect by cell type, showing cell type and brain tissue-specificity. Trauma-interactive eQTLs are more likely to lie in NF-kB (p=1.37E-04) and GR (p=1.46E-02) binding sites, implicating transcription factor binding as a mechanism of genotype-dependent stress response. We find that common genetic variation regulates transcriptional stress response in the post-mortem brain in a manner that is replicable in an hiPSC-derived neuronal model of stress. This regulation is cell type- and tissue-specific and offers a mechanistic understanding into variant-level regulation that may be further explored via integration with psychiatric disorder GWAS. [ABSTRACT FROM AUTHOR]

Background Injection of cement during vertebroplasty and kyphoplasty can leak into surrounding structures and could be symptomatic. Purpose To identify the sites and incidence of cement extravasation after kyphoplasty and vertebroplasty, and to evaluate their impacts on clinical outcomes. Material and Methods A retrospective review of 316 patients treated with kyphoplasty and vertebroplasty; 411 cases were included (223 kyphoplasty and 188 vertebroplasty). Cement extravasation was evaluated postoperatively by computed tomography (CT) scan of the spine. Clinical outcomes were assessed by visual analog scale (VAS) and Oswestry Disability Index (ODI). Results There was a statistically significant difference in the incidence rate of cement extravasation between vertebroplasty and kyphoplasty groups ( P < 0.04). The most common site of cement extravasation was in paravertebral soft tissues for vertebroplasty (n = 33, 40.7%) and for kyphoplasty (n = 30, 30%). In the subgroup where cement leaked into the intradiscal space, adjacent vertebral body fractures occurred in 3/26 vertebrae (11.5%) in the vertebroplasty group and in 2/18 vertebrae (11.1%) in the kyphoplasty group. Both groups showed a statistically significant decrease in both VAS ( P < 0.001) and ODI scores ( P < 0.001). There was no significantly difference in patient satisfaction between those who had cement extravasation and those who did not, in both groups. Conclusion Kyphoplasty has an advantage in terms of less risk of cement extravasation. However, this factor did not reflect on subsequent sequelae or final clinical outcomes. This study did not find a distinct correlation between intradiscal cement extravasation and increased risk of adjacent vertebral fractures. [ABSTRACT FROM AUTHOR]

Basal forebrain cholinergic neurons (BFCNs) are believed to be one of the first cell types to be affected in all forms of AD, and their dysfunction is clinically correlated with impaired short-term memory formation and retrieval. We present an optimized in vitro protocol to generate human BFCNs from iPSCs, using cell lines from presenilin 2 (PSEN2) mutation carriers and controls. As expected, cell lines harboring the PSEN2N141I mutation displayed an increase in the Aβ42/40 in iPSC-derived BFCNs. Neurons derived from PSEN2N141I lines generated fewer maximum number of spikes in response to a square depolarizing current injection. The height of the first action potential at rheobase current injection was also significantly decreased in PSEN2N141I BFCNs. CRISPR/Cas9 correction of the PSEN2 point mutation abolished the electrophysiological deficit, restoring both the maximal number of spikes and spike height to the levels recorded in controls. Increased Aβ42/40 was also normalized following CRISPR/Casmediated correction of the PSEN2N141I mutation. The genome editing data confirms the robust consistency of mutation-related changes in Aβ42/40 ratio while also showing a PSEN2-mutation-related alteration in electrophysiology. [ABSTRACT FROM AUTHOR]

Current methods to derive induced pluripotent stem cell (iPSC) lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of researchers to identify fully reprogrammed unique candidate clones from a mixed cell population containing transformed or partially reprogrammed cells and fibroblasts at an early time point post infection. Failure to select high quality colonies early in the derivation process results in cell lines that require increased maintenance and unreliable experimental outcomes. Here, we describe an improved method for the derivation of iPSC lines using fluorescence activated cell sorting (FACS) to isolate single cells expressing the cell surface marker signature CD13NEGSSEA4POSTra-1-60POS on day 7–10 after infection. This technique prospectively isolates fully reprogrammed iPSCs, and depletes both parental and “contaminating” partially reprogrammed fibroblasts, thereby substantially reducing the time and reagents required to generate iPSC lines without the use of defined small molecule cocktails. FACS derived iPSC lines express common markers of pluripotency, and possess spontaneous differentiation potential in vitro and in vivo. To demonstrate the suitability of FACS for high-throughput iPSC generation, we derived 228 individual iPSC lines using either integrating (retroviral) or non- integrating (Sendai virus) reprogramming vectors and performed extensive characterization on a subset of those lines. The iPSC lines used in this study were derived from 76 unique samples from a variety of tissue sources, including fresh or frozen fibroblasts generated from biopsies harvested from healthy or disease patients. [ABSTRACT FROM AUTHOR]

ABSTRACT The New York Stem Cell Foundation's 'Sixth Annual Translational Stem Cell Research Conference' convened on October 11-12, 2011 at the Rockefeller University in New York City. Over 450 scientists, patient advocates, and stem cell research supporters from 14 countries registered for the conference. In addition to poster and platform presentations, the conference featured panels entitled 'Road to the Clinic' and 'The Future of Regenerative Medicine.' [ABSTRACT FROM AUTHOR]

The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange. [ABSTRACT FROM AUTHOR]

We have generated a controlled and manipulable resource that captures genetic risk for Alzheimer's disease: iPSC lines from 53 individuals coupled with RNA and proteomic profiling of both iPSC-derived neurons and brain tissue of the same individuals. Data collected for each person include genome sequencing, longitudinal cognitive scores, and quantitative neuropathology. The utility of this resource is exemplified here by analyses of neurons derived from these lines, revealing significant associations between specific Aβ and tau species and the levels of plaque and tangle deposition in the brain and, more importantly, with the trajectory of cognitive decline. Proteins and networks are identified that are associated with AD phenotypes in iPSC neurons, and relevant associations are validated in brain. The data presented establish this iPSC collection as a resource for investigating person-specific processes in the brain that can aid in identifying and validating molecular pathways underlying AD. [Display omitted] • Generation and characterization of iPSC lines from 53 deeply phenotyped aged humans • Degree of congruence in expression profiles between iNs and brain of the same person • Association of cognitive decline and measures of Aβ and tau in iPSC-derived neurons • Identification and validation of PP1 as a molecular link between LOAD PRS, Aβ, and tau In this study, Lagomarsino et al. describe the generation of an iPSC collection from 53 deeply phenotyped individuals. These lines are coupled to RNA-seq and proteomic profiling of both iPSC neurons and brain of the same individuals. Using this system, biological insights are uncovered regarding the molecular mechanisms underlying Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Abstract: The present study explored the manner in which hand position may affect visual processing. We studied three classic visual attention tasks (visual search, inhibition of return, and attentional blink) during which the participants held their hands either near the stimulus display, or far from the display. Remarkably, the hands altered visual processing: people shifted their attention between items more slowly when their hands were near the display. The same results were observed for both visible and invisible hands. This enhancement in vision for objects near the hands reveals a mechanism that could facilitate the detailed evaluation of objects for potential manipulation, or the assessment of potentially dangerous objects for a defensive response. [Copyright &y& Elsevier]

We have reported previously that retinal pigment epithelium (RPE) differentiated from induced pluripotent stem cells (iPSC) generated from fibroblasts of patients with age-related macular degeneration (AMD) exhibit a retinal degenerative disease phenotype and a distinct transcriptome compared to age-matched controls. Since the genetic composition of the iPSC and RPE are inherited from fibroblasts, we investigated whether differential behavior was present in the parental fibroblasts and iPSC prior to differentiation of the cell lines into RPE. Principal component analyses revealed significant overlap (essentially no differences) in the transcriptome of fibroblasts between AMD and controls. After reprogramming, there was no significant difference in the transcriptome of iPSC generated from AMD versus normal donors. In contrast, the transcriptome of RPE derived from iPSC segregated into two distinct clusters of AMD-derived cells versus controls. Interestingly, mitochondrial dysfunction in AMD-derived RPE was evident after approximately two months in culture. Moreover, these differences in mitochondrial dysfunction were not evident in the parental fibroblasts and iPSC. This study demonstrates an altered transcriptome and impaired mitochondrial function in RPE derived from AMD patients versus controls, and demonstrates these differences are not present in the original fibroblasts or iPSC. These results suggest that pathology in AMD is triggered upon differentiation of parent cells into RPE. More study of this phenomenon could advance the current understandings of the etiology of AMD and the development of novel therapeutic targets. [Display omitted] • iPSC-RPE differentiated from AMD patients express a disease-related transcriptome. • Compared to age-matched controls, mitochondria are dysfunctional in AMD-RPE. • Disease-related phenotypes are absent in AMD-derived parental fibroblasts and iPSC. • Our model displays AMD phenotypes without extended culture or environmental insults. • These data are novel and have not been reported elsewhere in the literature. [ABSTRACT FROM AUTHOR]

Dysfunction and eventual loss of retinal pigment epithelial (RPE) cells is a hallmark of atrophic age-related macular degeneration (AMD), and linked to oxidative and nitrosative damage. Herein, we use a high-throughput screen (HTS) to identify compounds that protect human RPE cells from oxidative stress-induced cell death and elucidate the possible mechanism of action. HTS was used to identify compounds that protect RPE cells from oxidative damage. We tested the identified compound(s) in models of RPE stress, including tert -butyl hydroperoxide (TBHP) exposure, ultraviolet-B (UV-B)-mediated light damage and nitrosative stress to the basement membrane using ARPE-19 cells, primary human RPE cells and induced-pluripotent stem cell (iPSC)-derived RPE cells from patients with AMD. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect gene expression of oxidative stress- and apoptosis-related genes and mitochondrial function was measured using a Seahorse XF96 analyzer to elucidate possible mechanisms of action. Five thousand and sixty-five compounds were screened, and of these, 12 compounds were active based on their ability to improve cell viability after exposure to TBHP. After chemical structure review, we identified ciclopirox olamine as a potent inhibitor of oxidative damage to RPE cells. Ciclopirox olamine increased cell viability in ARPE-19 cells treated with TBHP, UV-B light or on nitrite-modified extracellular matrix (ECM) by 1.68-fold, 1.54-fold and 4.3-fold, respectively (p < 0.01). Treatment with TBHP altered expression of genes related to oxidative stress and apoptosis, which was reversed by pretreatment with ciclopirox olamine. Ciclopirox olamine improved mitochondrial function in TBHP-exposed ARPE-19 cells and iPSC-derived RPE cells. Ciclopirox olamine protected primary human RPE cells and iPSC-derived RPE cells from the oxidative stress or damaged basement membrane. HTS of bioactive Food and Drug Administration (FDA)-approved libraries and follow-up studies can be used to identify small molecules (including ciclopirox olamine) that protect RPE cells exposed to various stressors associated with disease progression of AMD. This strategy can be used to identify potential compounds for treatment and prevention of AMD. • A high-throughput screen (HTS) was developed to identify compounds that protect human RPE cells from oxidative damage. • Ciclopirox olamine protects RPE cells from oxidative damage and nitrosative damage to the basement membrane. • This HTS protocol can be used to identify potential compounds that may prevent or delay the progression of atrophic AMD. [ABSTRACT FROM AUTHOR]