RESEARCH ARTICLE
Reversal of Retinal Vascular Changes Associated with Ocular Neovascularization by Small Molecules: Progress toward Identifying Molecular Targets for Therapeutic Intervention
Michael DeNiroa*, 1, 2, Futwan Al-Mohanna
Article Information
Identifiers and Pagination:
Year: 2011Volume: 4
First Page: 75
Last Page: 95
Publisher Id: TODIAJ-4-75
DOI: 10.2174/1876524601104010075
Article History:
Received Date: 3/07/2010Revision Received Date: 13/01/2011
Acceptance Date: 16/01/2011
Electronic publication date: 28/3/2011
Collection year: 2011
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The elucidation of the molecular pathogenesis of ocular disease provides candidate targets for treatment. Animal models allow for identification and quantitation of ocular diseases. By gaining insight regarding the molecular signals involved in various types of ocular angiogenesis, general concepts can emerge that may apply to other settings, including tumor angiogenesis. The hypoxia inducible factor-1 (HIF-1) pathway is relatively well understood and serves as a good example of how knowledge of the biological responses to hypoxia can translate into new therapies. Furthermore, HIF pathway can be used as a therapeutic target and that the manipulation of the HIF pathway at several points has potential use for the treatment of oxygen-dependent diseases in retina. However, there are numerous other molecular and cellular responses to hypoxia that are independent of HIF-1, perhaps each with unique oxygen sensors. Despite participation of multiple stimulatory factors for ocular neovascularization (NV), vascular endothelial growth factor (VEGF) emerges as a pivotal player, thus manipulation of VEGF signaling represents an important therapeutic strategy. While most studies have focused on prevention of ocular NV, regression of new vessels is desirable and is achievable with various small molecules. Screens are underway to identify and test the efficacy of these small-molecules to target various mechanisms involved in ocular NV. These small molecules might represent an important component of novel combination therapies to target various molecular signaling mechanisms in neovascular tissues.