Purpose: Previous work in our lab using the electroretinogram has functionally characterized the bovine growth hormone expressing (bGH) mouse as having depressed oscillatory potentials (OPs) in comparison to wild-type (WT) littermates (1). A microarray analysis of the retina was therefore performed to identify candidate genes contributing to this phenotype. Methods: Total RNA was extracted from the retinas of 6 WT and 6 bGH mice by BioServe (Beltsville, MD). The expression level of 29,922 gene transcripts was measured using the Phalanx Biotech OneArray (Palo Alto, CA). Hierarchical clustering and functional gene-set analysis was performed on the resulting data to compare the retina of WT and bGH mice. Results: Gene-sets associated with Angiogenesis revealed 13 member genes in the retinas of bGH mice that had significant alterations (P<0.05) in their expression patterns in comparison with WT mice. Similarly, 52 genes associated with Apoptosis were altered, as were 8 genes associated with Diabetes, 12 with Neurotransmission, 10 with Neurotrophins, and 5 with the Janus-kinase (JAK) signaling pathways. In the Angiogenesis gene set for bGH mice, vascular endothelial growth factor (VEGF) receptor 2 precursor expression was increased to 134% of WT levels, while VEGF-A precursor was increased to 123% of WT levels. Pro-apoptotic transcripts of death-inducer obliterator 1 were reduced to 71% of WT levels. Transcripts for 6-phosphofructo-2-kinase/fructose- 2,6-biphosphatase 3, an enzyme important for glycolysis with involvement in diabetes, was upregulated to 146% of WT levels. There were significant changes to members of neurotransmission and neurotropic gene sets, including ATP-sensitive inward rectifier potassium channel 12 (118%), somatostatin receptor type 1 (91%), and insulin-like growth factor-binding protein 6 precursor (79%). Lastly, in the JAK pathway, suppressor of cytokine signaling 2 was upregulated to 154% of WT levels. Conclusion: Mice overexpressing growth hormone show a defect in the ERG analogous to that seen in diabetic retinopathy and retinopathy of prematurity. The results of this study indicate that the defect in these mice may be caused by alterations in vascular function (Vegfa, Kdr), altered cell survival in development (Bnip1, etc.) or changes in several genes linked to diabetes (Mapk8, PFkfb3). The changes in neurotransmission-linked gene expression may be directly responsible for the changes seen in ERG. In particular, genes of the Agxt family are linked to glycine metabolism in retinal amacrine cells, which are likely cellular mediators of the OPs. Changes in the Janus-kinase pathway reflect the heightened GH signaling (Socs2). These changes in gene expression occurred independently of gross morphological changes in the retina, as no significant differences were seen in cell counts or retinal zonation.