Background and purposes MicroRNAs (miRNAs) are small, noncoding RNA molecules of 18 to 25 nucleotides. They modulate protein expression by binding to complementary or partially complementary target messenger RNAs (mRNAs) and thereby target the mRNA for degradation or translational inhibition. The discovery of miRNAs has broadened an overall understanding of the mechanisms that regulate gene expression, with the addition of an entirely novel level of regulatory control.  In the eyes, many miRNAs have been identified in the past few years. In addition, miRNAs have been evaluated for their roles in diverse physiological and pathological processes, including retinal development, angiogenesis and degenerative disorders. Retinal ischemia-reperfusion injury has been implicated in the pathogenesis of many diseases/disorders including retinal artery occlusion, diabetic retinopathy and even glaucoma. This study aims to provide a miRNA signature of retinal ischemia reperfusion injury and determine the miRNAs and their target mRNAs in relation to neuroprotection, in order to further understand the underlying mechanisms of these disorders. 
Methods Long Evan rats subjected to transient high intraocular pressure were reperfused for various periods of time from 0 hours to 7 days. Retinal samples were harvested. MiRNA expression profiling and mRNA microarray of retina were carried out, and the data were validated by quantitative real-time polymerase chain reaction. The retinal miRNAs were correlated to prospective mRNA targets, which were then compared with our mRNA dataset with the aid of bioinformatic methods. Ingenuity Pathway Analysis (IPA) was carried out for the genes that were generated from the matching.
Results Our data revealed an involvement of miRNA regulation in retinal ischemia-reperfusion injury, with differentially expressed profiling of miRNAs at different time points in ischemic retina vs. sham controls.  Among the differentially expressed miRNAs, several miRNAs previously identified to be an effector of neuroprotection were detected, including miR-21, -92a, -130a and -223 etc.  In addition, other miRNAs such as miR-128 and -185, etc., were determined as new predicted regulators for genes that function in neuroprotection. The IPA analysis of the corresponding target genes revealed the involvement of multiple pathways relating to apoptosis, inflammation and neuroprotection. 
Conclusions Further investigation on the roles of miRNAs in retinal ischemia is needed  in order for enriching our understanding of retinal ischemia-related disorders.   Our study may provide new strategies and targets for the treatment of these disorders and miRNA-based novel treatment may be developed once the roles of miRNAs in the pathogenesis of these disorders are identified.   (Supported by NIH/NEI grant R01EY017594)