Orally active multi-functional antioxidants for the treatment of cataracts and AMD

Autor: James Randazzo, Peng Zhang, P. F. Kador, Karen Blessing
Rok vydání: 2009
Předmět:
Zdroj: Acta Ophthalmologica. 87
ISSN: 1755-3768
1755-375X
DOI: 10.1111/j.1755-3768.2009.3445.x
Popis: Age-related cataract and neurodegeneration has been linked to oxidative stress and increased lenticular levels of Fe and Cu, which can contribute to ROS generated through the Fenton Reaction. Since both antioxidants and chelating agents have both been reported to reduce experimental cataracts, we have synthesized a new class of antioxidants (JHX-4 and its dimethoxy analog JHX-8) containing a novel 2-amino-4-hydroxylpyrimidine ring system that selectively chelates Fe and Cu. In vitro studies in human lens epithelial cells and retinal pigment epithelial cells demonstrate that these compounds can reduce ROS generated by H2O2, endoplasmic reticulum (ER) stress, or Fenton’s reaction. In vivo studies demonstrate that these compounds accumulate in the lens and retina after oral administration. In Long-Evans rats receiving whole head irradiation, these compounds delayed cataract formation proportional to the tissue levels of drug achieved. Compared to untreated rats, treatment with JHX-4 and -8 delayed the formation of PSC punctuate opacities in 50% of animals by 53 and 58 days, respectively and lens PSC opacities by 38 and 47 days, respectively. In vivo neuroprotection studies are currently in progress. Supported by NIH EY016460-01.
Databáze: OpenAIRE
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