Apoptosis of the mammalian retina and lens

Papermaster, David S.

doi:10.1038/sj.cdd.4400210

Cited by 15 publications

(3 citation statements)

References 41 publications

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“…Due to limitations in space, this article focuses on those studies which directly relate to the apoptosis-like changes associated with fibre cell differentiation. For a more comprehensive overview of the field the interested reader should refer to the recent reviews published on this topic [124,129,130].…”

Section: P53 and Denucleationmentioning

confidence: 99%

Lens Fibre Cell Differentiation – A Link with Apoptosis?

Dahm¹

1999

Ophthalmic Res

101

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During the process of terminal differentiation, the fibre cells in the eye lens undergo many changes that are reminiscent of apoptotic/necrotic changes. Mitochondria, for instance, undergo permeability transition and nuclear degradation is accompanied by chromatin condensation, disintegration of the nucleolus, dissolution of the nuclear lamina, nuclear pore clustering and fragmentation of the DNA into oligonucleosomal fragments. As during apoptosis, members of the caspase family of proteases were shown to be active during fibre cell differentiation and Bcl-2 overexpression was demonstrated to block normal differentiation of lens cells. In this review, the current knowledge of the sequence of events during cell death is summarised and contrasted with events during lens fibre cell differentiation. Due to the numerous similarities between these processes, lens fibre cell differentiation is suggested to represent an attenuated form of cell death.

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Section: P53 and Denucleationmentioning

confidence: 99%

Lens Fibre Cell Differentiation – A Link with Apoptosis?

Dahm¹

1999

Ophthalmic Res

101

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“…To date very little has been reported on the role of p53 in the developing eye. Since apoptosis is required for development of the mammalian eye (see Papermaster, 1997, for recent review), and since p53 is now known to be required for some apoptotic developmental processes, we decided to ascertain the extent to which this gene is involved in normal eye development. In order to do this we have systematically examined mice with a target disruption of the p53 gene.…”

Section: Introductionmentioning

confidence: 99%

High frequency of persistent hyperplastic primary vitreous and cataracts in p53-deficient mice

et al. 1998

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In order to investigate whether the p53 gene product plays a role in normal eye development, age matched p53-deficient mice and wild-type controls were sacrificed from day 2 to day 21 after birth. Eyes were paraffin-embedded and sectioned. Serial sections were taken at the level of the tunica vasculosa lentis and the hyaloid artery. The terminal dUTP nick-end labelling technique (TUNEL) was used to detect the number of cells displaying DNA fragmentation within these structures. Eyes were also prepared for scanning electron microscopy and resin embedded for semi-thin sections. Adult wild-type mice and p53-deficient mice were 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 normally regresses during eye development. In adult animals there was also a high frequency of cataracts. Using morphological assessment and TUNEL we could show that in normal mice, regression of the primary vitreous, which includes the hyaloid artery, the vasa hyaloidea propria as well as the tunica vasculosa lentis, occurs via apoptotic cell death within 5 ± 6 weeks after birth. The number of TUNEL-positive cells within these 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 hyperplastic primary vitreous (PHPV) described in humans. As in humans, PHPV in mice resulted in the development of cataracts. We have identified a role for p53-dependent apoptosis in the regression of the hyaloid vasculature 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.

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“…In den letzten Jahren konnte sowohl im Tiermodell [9,43] als später auch im Menschen [36] gezeigt werden, dass alle bekannten RP-Formen in die gemeinsame Endstrecke der Apoptose münden [41]. Daneben führen auch verschiedene Formen von zellulärem Stress in der Netzhaut zum Zelltod durch Apoptose: helles Fluoreszenzlicht im Modell der lichtinduzierten Netzhautdegeneration [46,47], Applikation von Noxen wie Iodoacetat und Methylnitrosurea (MNU) [50] sowie eine induzierte Minderperfusion [8].…”

Section: Apoptoseunclassified

Therapieversuche bei RP: Licht am Ende des Tunnels?12

Abegg¹,

Hafezi²,

Wenzel³

et al. 2000

Klin Monatsbl Augenheilkd

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Retinitis pigmentosa (RP) is a hereditary retinal dystrophy which leads to severe visual impairment or blindness and affects about 3.5/1000 of individuals in the industrial world. During the past decades, numerous animal models carrying mutations analogous to mutations in human RP have been studied to elucidate the molecular mechanisms leading to apoptotic photoreceptor cell death in this disease. Up to date, there is no effective treatment to influence the fatal outcome of RP. Recent progress in basic research promotes the development of new therapeutic strategies. In order to restore visual function in blind individuals, the development of electronic photoreceptor prosthesis is being investigated by several researchgroups. Other promising approaches are somatic gene therapy, the application of growth factors and/or pharmacological agents and the inhibition of photoreceptor cell death by interfering with the apoptotic pathway. However, a better understanding of the molecular events leading to cell loss due to photoreceptor apoptosis will be essential for the development of effective treatment.

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Apoptosis of the mammalian retina and lens

Cited by 15 publications

References 41 publications

Lens Fibre Cell Differentiation – A Link with Apoptosis?

Lens Fibre Cell Differentiation – A Link with Apoptosis?

High frequency of persistent hyperplastic primary vitreous and cataracts in p53-deficient mice

Therapieversuche bei RP: Licht am Ende des Tunnels?12

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