Publications by authors named "Michael Margolis"

9 Publications

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Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds.

Small 2019 09 13;15(39):e1903147. Epub 2019 Aug 13.

Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void-forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross-linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co-injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross-linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process.
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http://dx.doi.org/10.1002/smll.201903147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761037PMC
September 2019

Shields Gray Crescents Masquerading as Glaucomatous Cupping of the Optic Nerve Head.

Ophthalmol Glaucoma 2018 Sep - Oct;1(2):99-107. Epub 2018 Aug 7.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Electronic address:

Purpose: Gray crescents characterized by darkly pigmented regions on the optic nerve head could make assessment of cupping difficult by obscuring the true anatomic disc border. On slit-lamp examination, 2 morphologically distinct types of gray crescents at the curved disc boundary exist. The in vivo histologic characteristics differentiating these 2 types are described using spectral-domain (SD) OCT.

Methods: A prospective interventional case series in a single tertiary referral center. Sixteen eyes of 10 patients with gray crescents determined through clinical examination and fundus photography underwent cross-sectional optic nerve head and parapapillary imaging using high-resolution SD OCT. In vivo histology of gray crescents was characterized.

Results: In SD OCT images across the areas of gray crescent, type A gray crescents represent regions where the retinal pigment epithelium (RPE)-Bruch's membrane complex is absent and the dark underlying choroid is directly visible. In contrast, type B gray crescents represent regions of the retina where the RPE is clumped or thickened, typically appearing to be folded upon itself, revealing the embryonic continuity of the RPE and neuroretina.

Conclusions: Shields type A and B gray crescents appear different clinically because histologically they represent differences in RPE. Type A grey crescents lack RPE, whereas type B crescents have thickened, folded RPE. Gray crescents can obscure the true disc border and result in pseudo-cupping of the optic nerve head. Identification of gray crescents is clinically important because failure to recognize pseudo-cupping can contribute to overdiagnosis of glaucoma.
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http://dx.doi.org/10.1016/j.ogla.2018.08.001DOI Listing
August 2018

Phospholipid secretions of organ cultured ciliary body.

J Cell Biochem 2018 03 27;119(3):2556-2566. Epub 2017 Oct 27.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Homeostasis of intraocular pressure (IOP) is important for the maintenance of anterior eye anatomic integrity, minimizing pressure-associated damage to the optic nerve, and maintaining a pressure gradient for blood flow to the eye. IOP is regulated by equilibrium between aqueous humor (AH) production and its outflow. The ciliary body (CB) is thought to actively secrete AH. However, whether AH composition and in particular, its phospholipids are entirely due to CB secretion remains uncertain. Comparison of phospholipids released by cultured CB, phospholipids present within CB tissue, within AH, and within blood and serum are consistent with release of most phospholipids into the AH by the CB. Treatment of CB in culture with timolol, a non-specific beta-adrenergic antagonist, alters the release of phospholipids by CB into the media. However, dorzalamide, a carbonic anhydrase inhibitor that reduces production of AH, does not affect phospholipid release thereby suggesting timolol, which also decreases IOP through decreased AH outflow, affects other physiological homeostatic mechanisms regulating aqueous outflow. These outflow changes also affect the composition of secreted phospholipids. We present evidence that release of lipids by the CB has a prolonged survival effect on cultured primary TM cells and TM tissue.
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http://dx.doi.org/10.1002/jcb.26419DOI Listing
March 2018

Green disease in optical coherence tomography diagnosis of glaucoma.

Curr Opin Ophthalmol 2017 Mar;28(2):139-153

aBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida bCurrent Address: Fillmore Eye Clinic, Alamogordo, New Mexico, USA.

Purpose Of Review: Optical coherence tomography (OCT) has become an integral component of modern glaucoma practice. Utilizing color codes, OCT analysis has rendered glaucoma diagnosis and follow-up simpler and faster for the busy clinician. However, green labeling of OCT parameters suggesting normal values may confer a false sense of security, potentially leading to missed diagnoses of glaucoma and/or glaucoma progression.

Recent Findings: Conditions in which OCT color coding may be falsely negative (i.e., green disease) are identified. Early glaucoma in which retinal nerve fiber layer (RNFL) thickness and optic disc parameters, albeit labeled green, are asymmetric in both eyes may result in glaucoma being undetected. Progressively decreasing RNFL thickness may reveal the presence of progressive glaucoma that, because of green labeling, can be missed by the clinician. Other ocular conditions that can increase RNFL thickness can make the diagnosis of coexisting glaucoma difficult. Recently introduced progression analysis features of OCT may help detect green disease.

Summary: Recognition of green disease is of paramount importance in diagnosing and treating glaucoma. Understanding the limitations of imaging technologies coupled with evaluation of serial OCT analyses, prompt clinical examination, and structure-function correlation is important to avoid missing real glaucoma requiring treatment.
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http://dx.doi.org/10.1097/ICU.0000000000000353DOI Listing
March 2017

Residual and Dynamic Range of Retinal Nerve Fiber Layer Thickness in Glaucoma: Comparison of Three OCT Platforms.

Invest Ophthalmol Vis Sci 2015 Oct;56(11):6344-51

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Florida, United States.

Purpose: To estimate visual field (VF) sensitivity at which retinal nerve fiber layer (RNFL) thinning reaches the measurement floor and at which RNFL stops thinning (change points), the dynamic range of RNFL thickness, and the number of steps from normal to RNFL floor among three optical coherence tomography (OCT) devices.

Methods: Glaucomatous patients (n = 58) and healthy subjects (n = 55-60) prospectively underwent VF testing and RNFL thickness measurement with Cirrus, Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were estimated with simple linear regression (SLR) and Bayesian change point (BCP) analyses. The dynamic range and number of steps to RNFL floor were determined.

Results: The average VF change points and corresponding residual thickness at the time RNFL stopped thinning were -22.2 dB and 57.0 μm (Cirrus), -25.3 dB and 49.2 μm (Spectralis), and -24.6 dB and 64.7 μm (RTVue). The RNFL dynamic ranges derived from SLR values were wider on Spectralis (52.6 μm) than on Cirrus (35.4 μm) and RTVue (35.5 μm); the corresponding number of steps to reach the RNFL floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue.

Conclusions: The relative VF sensitivity at which average RNFL thickness reaches the measurement floor, the residual layer thickness, and RNFL dynamic measurement range differ among the three devices. However, the number of steps from normal to the RNFL thickness floor is comparable.
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http://dx.doi.org/10.1167/iovs.15-17248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109982PMC
October 2015

Phospholipid makeup of the breast adipose tissue is impacted by obesity and mammary cancer in the mouse: Results of a pilot study.

Biochimie 2015 Jan 18;108:133-9. Epub 2014 Nov 18.

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address:

Obesity, an established risk factor for breast cancer (BC), is associated with systemic inflammation. The breast contains adipose tissue (bAT), yet whether it plays a role in BC progression in obese females is being intensively studied. There is scarce knowledge on the lipid composition of bAT in health and disease. The purpose of this pilot study was: 1) to determine whether obesity and BC are associated with inflammatory changes in bAT 2) to analyze for the first time the lipid profile of bAT in obese and lean mammary tumor-bearing and normal mice. Syngeneic E0771 mammary tumor cells were implanted into the mammary fat pad of lean and diet-induced obese C57BL/6 mice. BATs were analyzed four weeks after tumor cell inoculation by immunohistochemistry and mass spectrometry. Phospholipids were identified and subjected to ratiometric quantification using a TSQ Quantum Access Max triple quadrupole mass spectrometer utilizing precursor ion scan or neutral ion loss scan employing appropriate class specific lipid standards in a two step quantification process. Four main classes of phospholipids were analyzed: phosphatidylcholines phosphatidylserines, phosphatidylethanolamines and phosphatidylinositols. Our results showed that bAT in obese (normal and tumor-bearing) mice contained hypertrophic adipocytes compared with their corresponding samples in lean mice; higher numbers of macrophages and crown-like structures were observed in obese tumor bearers compared to obese normal mice. BAT from normal obese mice revealed higher concentrations of phosphatidylethanolamines. Furthermore, bAT from tumor-bearing mice expressed higher phosphatidylcholines than that from non-tumor bearing mice, suggesting the presence of the tumor is associated with phosphatidylcholines. Conversion of phosphatidylethanolamines to phosphatidylcholines will be investigated in E0771 cells. Additional studies are projected to investigate macrophage activation by these specific classes of phospholipids. Occurrence of triglycerides and free fatty acids will be examined in bAT and similar lipidomic analyses will be carried out visceral adipose tissue, highly inflamed in obesity.
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http://dx.doi.org/10.1016/j.biochi.2014.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294219PMC
January 2015

Review of application of mass spectrometry for analyses of anterior eye proteome.

World J Biol Chem 2014 May;5(2):106-14

Sherif Elsobky, Ashley M Crane, Michael Margolis, Teresia A Carreon, Sanjoy K Bhattacharya, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, United States.

Proteins have important functional roles in the body, which can be altered in disease states. The eye is a complex organ rich in proteins; in particular, the anterior eye is very sophisticated in function and is most commonly involved in ophthalmic diseases. Proteomics, the large scale study of proteins, has greatly impacted our knowledge and understanding of gene function in the post-genomic period. The most significant breakthrough in proteomics has been mass spectrometric identification of proteins, which extends analysis far beyond the mere display of proteins that classical techniques provide. Mass spectrometry functions as a "mass analyzer" which simplifies the identification and quantification of proteins extracted from biological tissue. Mass spectrometric analysis of the anterior eye proteome provides a differential display for protein comparison of normal and diseased tissue. In this article we present the key proteomic findings in the recent literature related to the cornea, aqueous humor, trabecular meshwork, iris, ciliary body and lens. Through this we identified unique proteins specific to diseases related to the anterior eye.
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http://dx.doi.org/10.4331/wjbc.v5.i2.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050106PMC
May 2014

Impact of missing data in evaluating artificial neural networks trained on complete data.

Comput Biol Med 2006 May;36(5):516-25

Biomedical Engineering Department, The University of Texas at Austin, 1 University Station, C0800, ENS617B, Austin, TX 78712, USA.

This study investigated the impact of missing data in the evaluation of artificial neural network (ANN) models trained on complete data for the task of predicting whether breast lesions are benign or malignant from their mammographic Breast Imaging and Reporting Data System (BI-RADS) descriptors. A feed-forward, back-propagation ANN was tested with three methods for estimating the missing values. Similar results were achieved with a constraint satisfaction ANN, which can accommodate missing values without a separate estimation step. This empirical study highlights the need for additional research on developing robust clinical decision support systems for realistic environments in which key information may be unknown or inaccessible.
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http://dx.doi.org/10.1016/j.compbiomed.2005.02.001DOI Listing
May 2006