The high recurrence rate of secondary cataract is caused by the autogenous differentiation activity of residual lens epithelial cells following extra-capsular lens removal. The objective of this study was to identify expression of miRNAs utilizing an established mouse secondary cataract surgery model. Accordingly, cataract surgery-associated changes in expression patterns of 55 miRNAs were detected by microarray analysis. To further study the potential cataract counter-regulative effect of miRNAs, a lens capsular bag in vitro model was employed. Correspondingly, selective miRNA manipulation by antimiR-184 and premiR-204 was able to attenuate cataract-associated cell proliferation and signs of endothelial to mesenchymal transition such as á-SMA expression. In addition, premiR-204 was able to attenuate cataract-associated target gene expression of the transcription factor Meis2. Examination of miRNA target binding sites for miR-184 and miR-204 revealed an extensive range of predicted target mRNA sequences that were also target to a complex network of other cataract-associated miRNAs with possible opposing function. In summary, the identification of the cataractspecific miRNA expression pattern together with the observed in vitro attenuation of cataract characteristic appearance by manipulation of miR-184 and miR-204 expression suggest that secondary cataract in mice is controlled by a miR-184 and miR-204 competitive RNA network.