The Relation of Vitamin a to Anophthalmos in Pigs

Hale, Fred

doi:10.1016/s0002-9394(35)90563-3

Cited by 198 publications

(63 citation statements)

References 5 publications

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“…Micropthalmia has been observed in mammalian embryos born from females fed with a diet deficient in vitamin A (Hale, 1937;Wilson, 1953). Thus, a reduction in eye size might occur when RA activity is blocked by expression of DNhRAR␣ in the chick retina.…”

Section: Expression Of Dnhrar␣ ␣ In the Chick Retina Leads To Reductimentioning

confidence: 99%

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

et al. 2005

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Asymmetric expression of several genes in the early eye anlagen is required for the dorsoventral (DV) and anteroposterior (AP) patterning of the retina. Some of these early patterning genes play a role in determining the graded expression of molecules that are needed to form the retinotectal map. The polarized expression of retinoic acid synthesizing and degrading enzymes along the DV axis in the retina leads to several zones of varied retinoic acid (RA)activity. This is suggestive of RA playing a role in DV patterning of the retina. A dominant-negative form of the retinoic acid receptor α(DNhRARα) was expressed in the chick retina to block RA activity. RA signaling was found to play a role in regulating the expression of EphB2,EphB3 and ephrin B2, three molecules whose graded expression in the retina along the DV axis is important for establishing the correct retinotectal map. Blocking RA signaling by misexpression of a RA degrading enzyme, Cyp26A1 recapitulated some but not all the effects of DNhRARα. It also was found that Vax, a ventrally expressed transcription factor that regulates the expression of the EphB and ephrin B molecules, functions upstream of, or in parallel to, RA. Expression of DNhRARα led to increased levels of RA-synthesizing enzymes and loss of RA-degrading enzymes. Activation of such compensatory mechanisms when RA activity is blocked suggests that RA homeostasis is very strictly regulated in the retina.

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Section: Expression Of Dnhrar␣ ␣ In the Chick Retina Leads To Reductimentioning

confidence: 99%

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

et al. 2005

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“…The structural integrity of the lens is important to the general development of the eye, and ablation of the lens through the targeted expression of a bacterial toxin in transgenic mice results in microphthalmia . Interestingly, vitamin A deficiency in mammals during development also causes microphthalmia (Hale 1937;Warkany and Schraffenberger 1946;Lammer et al 1985).…”

Section: Retinoids and Their Role In Lens Developmentmentioning

confidence: 99%

An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development.

Tini¹,

Otulakowski²,

Breitman³

et al. 1993

Genes Dev.

156

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The vertebrate lens is a classical system for examining mechanisms of tissue determination and differentiation, yet little is known about the signaling molecules controlling its development. Here, we report that retinoic acid IRA}, a substance known for its teratogenic effects on the eye and as a natural endogenous morphogenetic agent, acts as a regulator of gene expression in the lens. We have identified a novel type of RA response element (RARE) within the lens-specific mouse 7F-crystallin promoter, consisting of two (A/G)GGTCA motifs in an everted arrangement spaced by 8 nucleotides. This element {TF-RARE) mediates activation of the 7F-crystallin promoter by ligand-activated endogenous lens cell RA receptors (RARs) and confers RA responsiveness when linked to a heterologous promoter. 7F-RARE is bound in vitro by RAR/RXR heterodimers, and both receptors cooperate in vivo to trans-activate this element. These observations demonstrate a direct effect of RA on lens-specific gene expression and reveal a novel role for retinoids in the development and homeostasis of the mammalian eye.

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“…Hale 43 showed that vitamin A deficiency in female pigs produced anophthalmos and microphthalmos in its offspring. Since then, both hypo-and hypervitaminosis A have been known to be associated with foetal developmental defects.…”

Section: Vitamin Amentioning

confidence: 99%

Ocular teratogens: old acquaintances and new dangers

Tandon

Mulvihill

2009

Eye

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Recent research into animal studies has contributed significantly to understanding the pathophysiology of some well-known teratogens, such as alcohol. Techniques, such as positron emission tomography (PET) and retinal synaptogenesis studies, have helped determine the specific areas in the developing brain and ocular structures, which are targeted by various teratogens. In this article, we also highlight a few newer agents, such as benzodiazepines, with potential for ocular malformation and morbidity in the developing foetus.

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The Relation of Vitamin a to Anophthalmos in Pigs

Cited by 198 publications

References 5 publications

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina

An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development.

Ocular teratogens: old acquaintances and new dangers

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