Acucela

Publications

Acucela is developing orally-delivered visual cycle modulation (VCM) therapies that selectively target cells within the retina to protect visual acuity.

• N. Mata, R. Kubota, P. Dugel,. Visual Cycle Modulation: A Novel Therapeutic Approach For Treatment of GA in Dry AMD. Retinal Physician, May 2013: p. 21-23.
  
  
• R. Kubota, N. Boman, R. David, et al,. Safety And Effect On Rod Function of ACU-4429, A Novel Small-Molecule Visual Cycle Modulator. Retina, The Journal Of Retinal And Vitreous Diseases, 2012. 32(1): p. 183-88.
  
  
• Akula, J.D., et al,. Visual cycle modulation in neurovascular retinopathy. Exp Eye Res, 2010. 91(2): p. 153-61.
  
  
• Radu, R.A., et al., Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Proc Natl Acad Sci U S A, 2003. 100(8): p. 4742-7.
  
  
• Sieving, P.A., et al., Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy. Proc Natl Acad Sci U S A, 2001. 98(4): p. 1835-40.
  
  
• Bavik, C.O., et al., The retinal pigment epithelial membrane receptor for plasma retinol-binding protein. Isolation and cDNA cloning of the 63-kDa protein. J Biol Chem, 1993. 268(27): p. 20540-6.
  
  
• Hamel, C.P., et al., Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro. J Biol Chem, 1993. 268(21): p. 15751-7.
  
  
• Jin, M., et al., Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell, 2005. 122(3): p. 449-59.
  
  
• Jin, M., et al., Role of LRAT on the retinoid isomerase activity and membrane association of Rpe65. J Biol Chem, 2007. 282(29): p. 20915-24.
  
  
• Mata, N.L., et al., Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells. J Biol Chem, 2004. 279(1): p. 635-43.
  
  
• Bernstein, P.S., J.R. Lichtman, and R.R. Rando, Short-circuiting the visual cycle with retinotoxic aromatic amines. Proc Natl Acad Sci U S A, 1986. 83(6): p. 1632-5.
  
  
• Xue, L., et al., A palmitoylation switch mechanism in the regulation of the visual cycle. Cell, 2004. 117(6): p. 761-71.
  
  
• Golczak, M., et al., Metabolic basis of visual cycle inhibition by retinoid and nonretinoid compounds in the vertebrate retina. J Biol Chem, 2008. 283(15): p. 9543-54.
  
  
• Maeda, A., et al., Effects of potent inhibitors of the retinoid cycle on visual function and photoreceptor protection from light damage in mice. Mol Pharmacol, 2006. 70(4): p. 1220-9.
  
  
• Maeda, A., et al., Retinopathy in mice induced by disrupted all-trans-retinal clearance. J Biol Chem, 2008. 283(39): p. 26684-93.
  
  
• Eldred, G.E. and M.R. Lasky, Retinal age pigments generated by self-assembling lysosomotropic detergents. Nature, 1993. 361(6414): p. 724-6.
  
  
• Holz, F.G., et al., Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci, 1999. 40(3): p. 737-43.
  
  
• Reinboth, J.J., et al., Lipofuscin in the retina: quantitative assay for an unprecedented autofluorescent compound (pyridinium bis-retinoid, A2-E) of ocular age pigment. Exp Eye Res, 1997. 65(5): p. 639-43.
  
  
• Sparrow, J.R., et al., A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture. Invest Ophthalmol Vis Sci, 1999. 40(12): p. 2988-95.
  
  
• Sundelin, S., et al., Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity. Curr Eye Res, 1998. 17(8): p. 851-7.
  
  
• Liu, J., et al., The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane. J Biol Chem, 2000. 275(38): p. 29354-60.
  
  
• Mata, N.L., J. Weng, and G.H. Travis, Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci U S A, 2000. 97(13): p. 7154-9.
  
  
• Parish, C.A., et al., Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. Proc Natl Acad Sci U S A, 1998. 95(25): p. 14609-13.
  
  
• Sparrow, J.R., K. Nakanishi, and C.A. Parish, The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci, 2000. 41(7): p. 1981-9.