HIGH-FREQUENCY OF PERSISTENT HYPERPLASTIC PRIMARY VITREOUS AND CATARACTS IN P53-DEFICIENT MICE

In order to investigate whether the p53 gene product plays a role in n ormal eye development, age matched p53-deficient mice and wild-type co ntrols were sacrificed from day 2 to day 21 after birth, Eyes were par affin-embedded and sectioned, Serial sections were taken at the level of the tunica vasculosa lentis and the hyaloid artery, The terminal dU TP nick-end labelling technique (TUNEL) was used to detect the number of cells displaying DNA fragmentation within these structures, Eyes we re also prepared for scanning electron microscopy and resin embedded f or semi-thin sections, Adult wild-type mice and p53-deficient mice wer e examined ophthalmoscopically in vivo, Ophthalmoscopical examination of mice completely deficient in p53 revealed them to be normal except for the persistence of the hyaloid vasculature, a structure that norma lly regresses during eye development, In adult animals there was also a high frequency of cataracts, Using morphological assessment and TUNE L we could show that in normal mice, regression of the primary vitreou s, which includes the hyaloid artery, the vasa hyaloidea propria as we ll as the tunica vasculosa lentis, occurs via apoptotic cell death wit hin 5-6 weeks after birth, The number of TUNEL-positive cells within t hese structures was significantly reduced in the p53-deficient mice in which parts of the hyaloid vasculature persisted and developed into a fibro-vascular retrolental plaque analogous to persistent hyperplasti c primary vitreous (PHPV) described in humans. As in humans, PHPV in m ice resulted in the development of cataracts, We have identified a rol e for p53-dependent apoptosis in the regression of the hyaloid vascula ture and tunica vasculosa lentis, Our results provide further evidence for the importance of p53 in normal development and provide the first detailed evidence of its role in postnatal development in remodelling the developing eye.