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Journal of Ophthalmology
Volume 2017, Article ID 3034953, 19 pages
Review Article

A Critical Analysis of the Available In Vitro and Ex Vivo Methods to Study Retinal Angiogenesis

1Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
2Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
3Departamento de Cirurgia Cardiotorácica, Centro Hospitalar São João, Porto, Portugal
4Departamento de Oftalmologia, Centro Hospitalar São João, Porto, Portugal

Correspondence should be addressed to A. Rocha-Sousa; tp.pu.dem@asuosra

Received 11 April 2017; Revised 20 June 2017; Accepted 28 June 2017; Published 7 August 2017

Academic Editor: Biju B. Thomas

Copyright © 2017 A. F. Moleiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Angiogenesis is a biological process with a central role in retinal diseases. The choice of the ideal method to study angiogenesis, particularly in the retina, remains a problem. Angiogenesis can be assessed through in vitro and in vivo studies. In spite of inherent limitations, in vitro studies are faster, easier to perform and quantify, and typically less expensive and allow the study of isolated angiogenesis steps. We performed a systematic review of PubMed searching for original articles that applied in vitro or ex vivo angiogenic retinal assays until May 2017, presenting the available assays and discussing their applicability, advantages, and disadvantages. Most of the studies evaluated migration, proliferation, and tube formation of endothelial cells in response to inhibitory or stimulatory compounds. Other aspects of angiogenesis were studied by assessing cell permeability, adhesion, or apoptosis, as well as by implementing organotypic models of the retina. Emphasis is placed on how the methods are applied and how they can contribute to retinal angiogenesis comprehension. We also discuss how to choose the best cell culture to implement these methods. When applied together, in vitro and ex vivo studies constitute a powerful tool to improve retinal angiogenesis knowledge. This review provides support for researchers to better select the most suitable protocols in this field.