Hif1a and Hif2a can be safely inactivated in cone photoreceptors.
Sci Rep
; 9(1): 16121, 2019 11 06.
Article
em En
| MEDLINE
| ID: mdl-31695081
ABSTRACT
Impaired tissue oxygenation results in hypoxia and leads to the activation of hypoxia-inducible transcription factors (HIF). A chronic, HIF-triggered molecular response to hypoxia may be an important factor in the etiology of age-related macular degeneration (AMD) and is likely activated before any clinical manifestation of the disease. Thus, HIF1 and HIF2 recently emerged as potential therapeutic targets for AMD. To address and evaluate potential consequences of anti-HIF therapies for retinal physiology and function, we generated mouse lines that have Hif1a, or both Hif1a and Hif2a ablated specifically in cone photoreceptors. The knockdown of Hifs in cones did not cause detectable pathological alterations such as loss of cone photoreceptors, retinal degeneration or abnormalities of the retinal vasculature, had no impact on retinal function and resulted in a similar tolerance to hypoxic exposure. Our data indicate that HIF transcription factors are dispensable for maintaining normal cone function and survival in retinas of adult mice. This study provides the groundwork necessary to establish safety profiles for strategies aiming at antagonizing HIF1A and HIF2A function in cone photoreceptors for the treatment of retinal degenerative diseases that involve a hypoxic component such as AMD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Fotorreceptoras Retinianas Cones
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Degeneração Macular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça