PURPOSE:To generate a profile of genes expressed in the retina, RPE, and choroid after laser treatment and to identify genes that may contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. METHODS:Argon laser irradiation was delivered to the left eye of normal C57BL/6J mice (n = 30), with the right eye serving as the control in each animal. Three days after laser treatment, mice were culled, eyes enucleated, and the retinas dissected and pooled into respective groups. The total RNA of replicate samples was extracted, and expression profiles were obtained by microarray analysis. Data comparisons between control and treated samples were performed and statistically analyzed. RESULTS:Data revealed that the expression of 265 known genes and expressed sequence tags (ESTs) changed after laser treatment. Of those, 25 were found to be upregulated. These genes represented a number of biological processes, including photoreceptor metabolism, synaptic function, structural proteins, and adhesion molecules. Thus angiotensin II type 2 receptor (Agtr2), a potential candidate in the inhibition of VEGF-induced angiogenesis, was upregulated, whereas potential modulators of endothelial cell function, permeability factors, and VEGF inducers, such as FGF-14, FGF-16, IL-1beta, calcitonin receptor-like receptor (CRLR), and plasminogen activator inhibitor-2 (PAI2), were downregulated. CONCLUSIONS:In this study, genes were identified that both explain and contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. The molecular insights into the therapeutic effects of laser photocoagulation may provide a basis for future therapeutic strategies.