Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy.
Exp Mol Med
; 52(7): 1090-1101, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32641711
ABSTRACT
Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt's disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an albino Abca4-/- mouse model, the outer retina of which shows susceptibility to acute photodamage, to test the protective efficacy of a new polyunsaturated fatty acid lipophenol derivative. Anatomical and functional analyses demonstrated that a single intravenous injection of isopropyl-phloroglucinol-DHA, termed IP-DHA, dose-dependently decreased light-induced photoreceptor degeneration and preserved visual sensitivity. This protective effect persisted for 3 months. IP-DHA did not affect the kinetics of the visual cycle in vivo or the activity of the RPE65 isomerase in vitro. Moreover, IP-DHA administered by oral gavage showed significant protection of photoreceptors against acute light damage. In conclusion, short-term tests in Abca4-deficient mice, following single-dose administration and light exposure, identify IP-DHA as a therapeutic agent for the prevention of retinal degeneration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Doenças Retinianas
/
Luz
Limite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Ano de publicação:
2020
Tipo de documento:
Article