Delivery of Antisense Oligonucleotides to the Cornea.

Antisense oligonucleotides (ASOs) are synthetic nucleic acids that recognize complementary RNA sequences inside cells and modulate gene expression. In this study, we explore the feasibility of ASO delivery to the cornea. We used quantitative polymerase chain reaction to test the efficacy of a benchmark ASO targeting a noncoding nuclear RNA, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (), in a human corneal endothelial cell line, human corneas, and in mice. delivery was via intravitreal or intracameral injections as well as topical administration. The anti- ASO significantly reduced expression of in a corneal endothelial cell line. We achieved a dose-dependent reduction of target gene expression in endothelial tissue from human donor corneas. mouse experiments confirmed reduction in whole corneal tissue via intravitreal and intracameral routes, 82% and 71% knockdown, respectively ( < 0.001). Effects persisted up to at least 21 days, 32% ( < 0.05) and 43% ( < 0.05) knockdown, respectively. We developed protocols for the isolation and analysis of mouse corneal endothelium and observed reduction in expression upon both intravitreal and intracameral administrations, 64% ( < 0.05) and 63% ( < 0.05) knockdown, respectively. These data open the possibility of using ASOs to treat corneal disease.