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Dopamine is a neurotransmitter that mediates visual function in the retina and diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of blindness; however, the role of dopamine in retinal vascular dysfunction in DR remains unclear. Here, we report a mechanism of hyperglycemic memory (HGM)-induced retinal microvascular dysfunction and the protective effect of dopamine against the HGM-induced retinal microvascular leakage and abnormalities. We found that HGM induced persistent oxidative stress, mitochondrial membrane potential collapse and fission, and adherens junction disassembly and subsequent vascular leakage after blood glucose normalization in the mouse retinas. These persistent hyperglycemic stresses were inhibited by dopamine treatment in human retinal endothelial cells and by intravitreal injection of levodopa in the retinas of HGM mice. Moreover, levodopa supplementation ameliorated HGM-induced pericyte degeneration, acellular capillary and pericyte ghost generation, and endothelial apoptosis in the mouse retinas. Our findings suggest that dopamine alleviates HGM-induced retinal microvascular leakage and abnormalities by inhibiting persistent oxidative stress and mitochondrial dysfunction.

Amino acids Amino acids U 0400Highly Enantioselective Synthesis of α-Alkyl-alanines via the Catalytic Phase-Transfer Alkylation of 2-Naphthyl Aldimine tert-Butyl Ester by Using O(9)-Allyl-N(1)-2',3',4'-trifluorobenzylhydrocinchonidinium Bromide. -The title compounds are of biological interest. Best results are obtained at -35°C using the title bromide (Ia) as catalyst and RbOH as base. -(JEW, S.-S.; JEONG, B.-S.; LEE, J.-H.; YOO, M.-S.; LEE, Y.-J.; PARK, B.-S.; KIM, M.; PARK*, H.-G.; J. Org.

General MethodsThe 1 H-NMRs were recorded at 300 MHz, 400 MHz, and 500 MHz. The 13 C-NMRs were recorded at 75 MHz, 100 MHz, and 125 MHz. The chemical shifts were reported in ppm relative to CHCl 3 (δ 7.26) for 1 H-NMR and relative to the central CDCl 3 (δ 77.23) resonance for 13 C-NMR. Optical rotations were measured on a digital polarimeter. Melting points were not corrected. Flash column chromatography was carried out using silica gel (70~230 mesh). The enantiomeric excess (ee) of the products was determined by HPLC using 4.6 mm × 250 mm Chiralpak AD-H or OD-H columns. All solvents and commercially available chemicals were used without additional purification. Experimental Section 2-Phenyl-2-thiazoline-4-carboxylic acid methyl ester (12)To a methylene chloride solution (100 mL) of L-cysteine methyl ester hydrochloride (5.00 g, 29.13 mmol) and ethyl benzimidate hydrochloride (5.95 g, 32.04 mmol) was added triethylamine (6.08 mL, 43.69 mmol) and the reaction mixture was refluxed (6 h). After completion of the reaction, the reaction mixture was diluted with methylene chloride (500 mL), washed with saturated NaHCO 3 solution (70 mL) and brine (70 mL), dried over anhydrous MgSO 4 , filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes:EtOAc = 30:1) to afford 12 (5.71 g, 89% yield) as a white solid (mp 67 °C).