Abstract
Purpose: :
Retinal neovascularization involves a complex cascade of cellular processes. Analysis of retinal gene expression in two rodent models of oxygen-induced retinopathy (OIR) was peformed to identify commonalities from two models with a similar phenotype.
Methods: :
Three independent experiments were conducted for each species, using standard protocols for OIR induction. Retinal RNA was isolated at two timepoints, corresponding to early hypoxia (P13 in mouse, P15 in rat) and maximal retinal neovascularization (P18 in mouse, P20 in rat) and used to prepare probes for hybridization to rat Genome 230 2.0 or mouse Genome 430 2.0 GeneChip. Gene expression was compared between normal and experimental conditions for each species at each timepoint. Probesets with a step-up false discovery rate of ≤ 0.05 were considered significantly different. Results of comparative gene expression were classified into cellular functions and biological pathways. Changes in expression of selected genes were confirmed by quantitative rt-PCR.
Results: :
The number of genes and pathways showing significant change in expression for each of the four conditions, and the number of genes and pathways common to both species, are shown below. At the early timepoint, increased expression of members of the VEGF and ephrin receptor signaling pathways were identified in both species. At the later timepoint, increased expression involving four pathways were identified in common: ALS signaling, axonal guidance, ephrin receptor signaling, and hepatic fibrosis/stellate cell activation.
Conclusions: :
Known angiogenic pathways were confirmed, and additional biologically plausible genes and pathways were identified. This work serves as a comprehensive resource for the study of retinal neovascularization and identification of rational targets for antiangiogenic therapy.
Keywords: retinal neovascularization