Abstract: This study was conducted to elucidate the effect of bioconjugation of oligodeoxynucleotides with Lutein on antifibrotic activity using cultured adult human retinal pigment epithelial (ARPE-19) cells as model system. Fibrosis was induced in ARPE-19 cells by N-Nitrosodimethylamine (DMN) at a dose of 10 μL (diluted 1:100 with 0.15 M sterile NaCl). Oligodeoxynucleotides specific for Hepatocyte Growth Factor (HGF) and p38 Mitogen Activated Protein Kinase (MAPK) genes modified with a sulfhydryl group at the 3' end (500 nmol) was conjugated with 10 mg of Lutein. Expression of HGF, p38 MAPK and production of extracellular matrix proteins (ECM) such as collagen type I and fibronectin were assayed. The intracellular expression of Hepatocyte Growth Factor (HGF) and its receptor gene, p38 MAPK showed suppression in ARPE-19 cells treated with DMN+Lutein 15 μg/20 μL conjugated with oligodeoxynucleotides for HGF and p38 MAPK, respectively. A 50% of ARPE-19 cells showed an increase in type I collagen (582±92 pg) in DMN treated cells versus 220±42, p<0.001 (untreated) and it was 389±61 pg in cells treated with DMN+Lutein 15 μg/20 μL oligodeoxynucleotides conjugated. The fibronectin level was 1,422±60 pg in DMN treated cells versus 360±24, p<0.001 (untreated) and it was 760±59 pg in cells treated with DMN+Lutein 15 μg/20 μL oligodeoxynucleotides conjugated. These results demonstrate that bioconjugation of ODNs with Lutein would significantly suppress HGF/cMet, p38MAPK expression, collagen type I, fibronectin and quench the associated reactive oxygen species contributing for the progression of fibrosis in ARPE-19 cells.