The effect of retinal pigment epithelial cell patch size on growth factor expression
Abstract
The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function that occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.
- Authors:
-
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1185385
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biomaterials
- Additional Journal Information:
- Journal Volume: 35; Journal Issue: 13; Journal ID: ISSN 0142-9612
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; microcontact printing; retinal pigment epithelial; tight junctions; VEGF; in vitro model; micropatterning
Citation Formats
Vargis, Elizabeth A., Peterson, Cristen B., Morrell-Falvey, Jennifer L., Retterer, Scott T., and Collier, Charles Patrick. The effect of retinal pigment epithelial cell patch size on growth factor expression. United States: N. p., 2014.
Web. doi:10.1016/j.biomaterials.2014.01.016.
Vargis, Elizabeth A., Peterson, Cristen B., Morrell-Falvey, Jennifer L., Retterer, Scott T., & Collier, Charles Patrick. The effect of retinal pigment epithelial cell patch size on growth factor expression. United States. https://doi.org/10.1016/j.biomaterials.2014.01.016
Vargis, Elizabeth A., Peterson, Cristen B., Morrell-Falvey, Jennifer L., Retterer, Scott T., and Collier, Charles Patrick. Thu .
"The effect of retinal pigment epithelial cell patch size on growth factor expression". United States. https://doi.org/10.1016/j.biomaterials.2014.01.016. https://www.osti.gov/servlets/purl/1185385.
@article{osti_1185385,
title = {The effect of retinal pigment epithelial cell patch size on growth factor expression},
author = {Vargis, Elizabeth A. and Peterson, Cristen B. and Morrell-Falvey, Jennifer L. and Retterer, Scott T. and Collier, Charles Patrick},
abstractNote = {The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function that occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.},
doi = {10.1016/j.biomaterials.2014.01.016},
journal = {Biomaterials},
number = 13,
volume = 35,
place = {United States},
year = {Thu Jan 30 00:00:00 EST 2014},
month = {Thu Jan 30 00:00:00 EST 2014}
}
Web of Science
Works referenced in this record:
Surface engineering approaches to micropattern surfaces for cell-based assays
journal, June 2006
- Falconnet, Didier; Csucs, Gabor; Michelle Grandin, H.
- Biomaterials, Vol. 27, Issue 16
Plasma-induced chemical micropatterning for cell culturing applications: a brief review
journal, September 1999
- Ohl, A.; Schröder, K.
- Surface and Coatings Technology, Vol. 116-119
Defective Excitation-Contraction Coupling in Experimental Cardiac Hypertrophy and Heart Failure
journal, May 1997
- Gomez, A. M.
- Science, Vol. 276, Issue 5313
Engineering cell shape and function
journal, April 1994
- Singhvi, R.; Kumar, A.; Lopez, G.
- Science, Vol. 264, Issue 5159
Plasma stencilling methods for cell patterning
journal, May 2009
- Frimat, Jean-Philippe; Menne, Heike; Michels, Antje
- Analytical and Bioanalytical Chemistry, Vol. 395, Issue 3
Control of Human Embryonic Stem Cell Colony and Aggregate Size Heterogeneity Influences Differentiation Trajectories
journal, September 2008
- Bauwens, Céline Liu; Peerani, Raheem; Niebruegge, Sylvia
- Stem Cells, Vol. 26, Issue 9
Simple Approach to Micropattern Cells on Common Culture Substrates by Tuning Substrate Wettability
journal, May 2004
- Tan, John L.; Liu, Wendy; Nelson, Celeste M.
- Tissue Engineering, Vol. 10, Issue 5-6
Endothelial Cell Micropatterning: Methods, Effects, and Applications
journal, July 2011
- Anderson, Deirdre E. J.; Hinds, Monica T.
- Annals of Biomedical Engineering, Vol. 39, Issue 9
Micropatterning of living cells by laser-guided direct writing: application to fabrication of hepatic–endothelial sinusoid-like structures
journal, December 2006
- Nahmias, Yaakov; Odde, David J.
- Nature Protocols, Vol. 1, Issue 5
A microfabricated platform for high-throughput unconfined compression of micropatterned biomaterial arrays
journal, January 2010
- Moraes, Christopher; Wang, GongHao; Sun, Yu
- Biomaterials, Vol. 31, Issue 3
Emergence of Patterned Stem Cell Differentiation Within Multicellular Structures
journal, November 2008
- Ruiz, Sami Alom; Chen, Christopher S.
- Stem Cells, Vol. 26, Issue 11
The motility of normal and cancer cells in response to the combined influence of the substrate rigidity and anisotropic microstructure
journal, April 2008
- Tzvetkova-Chevolleau, Tzvetelina; Stéphanou, Angélique; Fuard, David
- Biomaterials, Vol. 29, Issue 10
Treating Age-Related Macular Degeneration – Interaction of VEGF-Antagonists with their Target
journal, August 2009
- Klettner, A.; Roider, J.
- Mini-Reviews in Medicinal Chemistry, Vol. 9, Issue 9
Expression and regulation of vascular endothelial growth factor in choroidal fibroblasts
journal, January 1995
- Kvanta, Anders
- Current Eye Research, Vol. 14, Issue 11
Pigment Epithelium-derived Factor Maintains Retinal Pigment Epithelium Function by Inhibiting Vascular Endothelial Growth Factor-R2 Signaling through γ-Secretase
journal, October 2009
- Ablonczy, Zsolt; Prakasam, Annamalai; Fant, James
- Journal of Biological Chemistry, Vol. 284, Issue 44
Patchy atrophy and lacquer cracks predispose to the development of choroidal neovascularisation in pathological myopia
journal, May 2003
- Ohno-Matsui, K.
- British Journal of Ophthalmology, Vol. 87, Issue 5
VEGF modulation of retinal pigment epithelium resistance
journal, December 2007
- Ablonczy, Zsolt; Crosson, Craig E.
- Experimental Eye Research, Vol. 85, Issue 6
The Tight Junction Associated Signalling Proteins ZO-1 and ZONAB Regulate Retinal Pigment Epithelium Homeostasis in Mice
journal, December 2010
- Georgiadis, Anastasios; Tschernutter, Marion; Bainbridge, James W. B.
- PLoS ONE, Vol. 5, Issue 12
Increased expression of angiogenic growth factors in age-related maculopathy
journal, February 1997
- Kliffen, M.; Sharma, H. S.; Mooy, C. M.
- British Journal of Ophthalmology, Vol. 81, Issue 2
Vascular endothelial growth factors and angiogenesis in eye disease
journal, January 2003
- Witmer, A.
- Progress in Retinal and Eye Research, Vol. 22, Issue 1
Brain atrophy in clinically early relapsing–remitting multiple sclerosis
journal, February 2002
- Chard, D. T.; Griffin, C. M.; Parker, G. J. M.
- Brain, Vol. 125, Issue 2
Long-Term Cognitive Impairments and Attentional Deficits in Patients with Cushing's Disease and Cortisol-Producing Adrenal Adenoma in Remission
journal, September 2012
- Ragnarsson, Oskar; Berglund, Peter; Eder, Derek N.
- The Journal of Clinical Endocrinology & Metabolism, Vol. 97, Issue 9
Works referencing / citing this record:
Printable Graphene Oxide Micropatterns for a Bio-Subretinal Chip
journal, July 2018
- Yang, Jia-Wei; Tseng, Ming-Liang; Fu, Yu-Min
- Advanced Healthcare Materials, Vol. 7, Issue 18
A bilayer photoreceptor-retinal tissue model with gradient cell density design: A study of microvalve-based bioprinting
journal, March 2018
- Shi, Pujiang; Tan, Yong Sheng Edgar; Yeong, Wai Yee
- Journal of Tissue Engineering and Regenerative Medicine, Vol. 12, Issue 5
A computational study of VEGF production by patterned retinal epithelial cell colonies as a model for neovascular macular degeneration
journal, August 2017
- Baker, Qanita Bani; Podgorski, Gregory J.; Vargis, Elizabeth
- Journal of Biological Engineering, Vol. 11, Issue 1
Effect of Daily Light on c-Fos Expression in the Suprachiasmatic Nucleus under Jet Lag Conditions
journal, January 2018
- Chen, Yulin; Yamaguchi, Yoshiaki; Suzuki, Toru
- ACTA HISTOCHEMICA ET CYTOCHEMICA, Vol. 51, Issue 2