A5067103220- Corneal Surgery and Treatments
- Corneal surgery and disorders
- Cell Adhesion Molecules Research
- Ocular Surface and Contact Lens
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Extracellular vesicles in disease
- Glaucoma and retinal disorders
- Nanoplatforms for cancer theranostics
- Protease and Inhibitor Mechanisms
- Angiogenesis and VEGF in Cancer
- Retinal Imaging and Analysis
- Advanced biosensing and bioanalysis techniques
- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- Wound Healing and Treatments
- Retinopathy of Prematurity Studies
- Retinal and Optic Conditions
- Caveolin-1 and cellular processes
- Mesenchymal stem cell research
- Glioma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Cellular Mechanics and Interactions
- Herpesvirus Infections and Treatments
- Ocular Disorders and Treatments
Cedars-Sinai Medical Center
2016-2025
University of California, Los Angeles
2016-2025
Broad Center
2021
California Institute for Regenerative Medicine
2017
Regenerative Medicine Institute
2013-2016
Neutrogena (United States)
2015
UCLA Health
2014
University of Regensburg
2011
Institute of Biomedical Science
2010
University of California System
2009
Abstract Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due their inability cross blood–brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB activation of local brain anti-tumor immune response. NIC mice...
Abstract Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, histological examinations support existence vascular-structural abnormalities β-protein (Aβ) deposits retinas AD...
Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly early stages of functional impairment, how they relate to progression brain remain largely unknown. To better understand pathological features AD retina, we conducted an extensive histopathological biochemical investigation postmortem retina tissues from 86 human donors. Quantitative examination superior inferior temporal retinas...
To study alterations of the extracellular matrix (ECM) and basement membrane (BM) components in human keratoconus corneas.Fifteen normal 13 corneas were characterized by immunofluorescence with antibodies to 23 ECM BM components.Keratoconus staining patterns for posterior nonscarred regions Descemet's normal. We focused on three areas corneas: (a) anterior corneal regions, (b) scarred (c) gaps Bowman's layer. In each these areas, consistent changes could be found. Nonscarred showed decreased...
Adult human corneal epithelial basement membrane (EBM) and Descemet's (DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes these during postnatal development.Thirty healthy adult corneas 10 from 12-day- 3-year-old children were studied by immunofluorescence with antibodies against BM components.Type IV collagen composition infant central EBM over Bowman's layer changed alpha1-alpha2 alpha3-alpha4 chains after 3 years life; in adult, retained...
OBJECTIVE Patients with diabetes are at an increased risk for developing corneal complications and delayed wound healing. This study investigated the effects of high glucose on epidermal growth factor receptor (EGFR) signaling epithelial healing in cornea. RESEARCH DESIGN AND METHODS Effects EGFR were cultured porcine corneas, human cells, corneas using Western blotting immunofluorescence. reactive oxygen species (ROS) glutathione levels pathways assessed primary respectively. The ligands...
Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood–brain barrier (BBB) tumor (BTB) and targeting specific types cells release into the cell cytoplasm. A polymeric nanobioconjugate based on biodegradable, nontoxic, nonimmunogenic polymalic acid a universal nanoplatform was used for design synthesis nanomedicine i.v. tumors. The passes BTB membrane using tandem monoclonal antibodies...
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive behavioral deficits, vision disturbances have been reported early stage of AD, well before diagnosis clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed.Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 age-matched wild type (WT)...
Abstract INTRODUCTION Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that retinal vascular tight junctions (TJs) compromised linked to status. METHODS TJ components Aβ expression capillaries larger blood vessels determined post mortem from 34 MCI or AD patients 27 normal controls correlated with neuropathology. RESULTS Severe decreases zonula occludens‐1 (ZO‐1) claudin‐5...
Abstract This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer’s disease (AD), exploring their connection status. Retinal cross-sections from predefined superior-temporal inferior-temporal subregions corresponding brains neuropathologically confirmed AD patients a clinical diagnosis either mild cognitive impairment (MCI) or dementia ( n = 45) were compared retinas age- sex-matched normal cognition 30) non-AD 4). isoforms,...
Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations individual BM components diabetic eyes, especially retinopathy (DR), obscure. To identify abnormalities the distribution of specific constituents, we analyzed cryostat sections human eyes obtained at autopsy (seven normal, five without DR, 13 with DR) by immunofluorescence antibodies to 30 extracellular matrix components. In non-DR no qualitative changes ocular were seen. some DR corneas, epithelial...
Differential diagnosis of brain magnetic resonance imaging (MRI) enhancement(s) remains a significant problem, which may be difficult to resolve without biopsy, can often dangerous or even impossible. Such MRI result from metastasis primary tumors such as lung breast, radiation necrosis, infections, new tumor (glioma, meningioma). Neurological symptoms are the same on initial presentation. To develop more precise noninvasive diagnostic method, we have engineered class poly(β-l-malic acid)...
Abstract Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal abnormalities resulting in compromised vision and blindness. LSCD can be potentially treated by transplantation of appropriate cells, which should easily expandable bankable. Induced pluripotent cells (iPSCs) are a promising source transplantable LESCs. The purpose this study was generate human iPSCs direct them limbal differentiation maintaining on natural substrata mimicking the native LESC niche, including...
MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in diseases remain unknown. Our purpose was to identify miRNAs altered the human diabetic cornea by microarray analysis, examine effects on wound healing cultured telomerase-immortalized epithelial cells (HCEC) vitro. Total RNA extracted from age-matched autopsy normal (n=6) central corneas, Flash Tag end-labeled, hybridized Affymetrix® GeneChip® miRNA Arrays. Select associated with were...
There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in tumor microenvironment important invasion and progression. In a panel 226 patient brain glioma samples, we found clinical correlation between expression vascular laminin-411 (α4β1γ1) with higher grade cancer stem cell (CSC) markers, Notch pathway members, CD133, Nestin, c-Myc. Laminin-411 overexpression also correlated recurrence rate shorter survival GBM patients. We...