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Nami Nishikiori1,2, Makoto Osanai2, Hideki Chiba2, Takashi Kojima2, Shuichiro Inatomi1,2, Hiroshi Ohguro1, Norimasa Sawada2Departments of 1Ophthalmology and 2Pathology, Sapporo Medical University School of MedicinePurpose: This study was conducted to investigate whether retinoic acids (RAs) had any effect on apoptosis during the development of diabetic retinopathy.Methods: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO) and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA) (seven mice) and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido] benzoic acid (Am580) (nine mice). The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay.Results: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean value and SD: 37.8 ± 6.9), whereas when diabetic mice were treated with RAs, the number of apoptotic cells significantly decreased (mean value and SD: 9.9 ± 6.4 for the seven ATRA-treated diabetic mice and 9.8 ± 5.9 for the nine Am580-treated diabetic mice) (p < 0.05).Conclusion: Treatment with RAs decreases apoptosis during the development of diabetic retinopathy.Keywords: retinoic acids, apoptosis, diabetic retinopathy, glial cell line-derived neurotrophic factor