Fibroblast growth factor-2 decreases hyperoxia-Induced photoreceptor cell death in mice

Haruhiko Yamada, Eri Yamada, Akira Ando, Noriko Esumi, Naba Bora, Jina Saikia, Ching Hwa Sung, Donald J. Zack, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Fibroblast growth factor-2 (FGF2) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of FGF2 in mice are equivocal. In this study, we used transgenic mice with increased expression of FGF2 in photoreceptors (rhodopsin promoter/FGF2 transgenics) to investigate the effects of sustained increased expression of FGF2 in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase β subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/FGF2 transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to FGF2 transgenic mice (P = 0.0001). These data indicate that increased expression of FGF2 in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that FGF2 protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.

Original languageEnglish (US)
Pages (from-to)1113-1120
Number of pages8
JournalAmerican Journal of Pathology
Volume159
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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