Gas6 Binding to Photoreceptor Outer Segments Requires γ-Carboxyglutamic Acid (Gla) and Ca2+ and is Required for OS Phagocytosis by RPE Cells in vitro

Hall, Michael O.; Obin, Martin S.; Prieto, Anne L.; Burgess, Barry L.; Abrams, Toshka A.

doi:10.1006/exer.2002.2030

Cited by 40 publications

(31 citation statements)

References 44 publications

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“…Gas6 interacts with receptor molecules (e.g. MERTK) on the surface of the RPE, and activates RPE cell signaling pathways leading to OS ingestion [18]. The mRNA level of these genes in the macula ranged from very high (Gas6) to very low (CD36), with most of them showing a medium expression (INTαV, MRC1, MERTK, INTβ5).…”

Section: Discussionmentioning

confidence: 99%

Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Kociok

Joussen

2006

Graefe's Arch Clin Exp Ophthalmol

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Whereas most of the analyzed genes expressed in RPE and choroid had equal mRNA expression levels in the macula and the periphery with donor dependent variations, there are important exceptions in genes that are involved in the maintenance of a specific vascular status in the macula (PEDF, VEGF and VEGR-R2) and in the recycling of rod outer segments (11-cis RDH). Applying this technique to the gene expression analysis of patients with AMD could identify those genes that are involved in molding of the disease.

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Section: Discussionmentioning

confidence: 99%

Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Kociok

Joussen

2006

Graefe's Arch Clin Exp Ophthalmol

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“…Thus, the sparing effect of VK in the aging rat retina is unlikely to reflect the growth factor or survivalpromoting activities of VKDPs such as Gas6 (Tsaioun, 1999;Tsaioun et al, 2000;Funakoshi et al, 2002;Yagami et al, 2002). Moreover, the absence of accelerated photoreceptor cell loss in rats fed the L diet suggests that, despite low levels of VK, g-carboxylation of Gas6 was sufficient to fully support mertk-mediated phagocytosis (Feng et al, 2002;Hall et al, 2002). This is possible, if mertkmediated phagocytosis is regulated by blood-borne, hepatic (i.e.…”

Section: Discussionmentioning

confidence: 85%

“…Mertk activation is required for daily phagocytosis of "old" photoreceptor disc membranes by the overlying retinal pigment epithelium (RPE) (Hall et al, 2001;Feng et al, 2002). Notably, whereas recombinant Gas6 fully stimulates mertk-dependent phagocytosis, Gas6 expressed in the presence of warfarin fails to do so (Hall et al, 2002). As defective phagocytosis results in photoreceptor cell death, these observations suggest a requirement for VK-dependent g carboxylation in photoreceptor cell survival.…”

Section: Introductionmentioning

confidence: 97%

Effects of Long-term Vitamin K (Phylloquinone) Intake on Retina Aging

Carrié

Ferland

Obin

2003

Nutritional Neuroscience

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Emerging evidence suggests neuroprotective functions of vitamin K and/or vitamin K-dependent proteins. We investigated the effect of dietary vitamin K on retina aging (thinning). Female Sprague-Dawley rats were maintained from weaning on low (80 microg kg(-1) diet), adequate (500 microg kg(-1) diet) or high (2000 microg kg(-1) diet) levels of vitamin K1 (phylloquinone). Relative concentrations of brain vitamin K associated with these diets were 1: 3.3: 25 (K1) and 1: 2.7: 9.0 (menaquinone-4). Histomorphometry of old (21 month) rats revealed positive associations between vitamin K and thickness of retina layers, especially in the equatorial/peripheral retina. No association of diet and retina thickness was detected among young (6 month) animals. The sparing effect of vitamin K in the retina was most evident in the inner plexiform layer and in the photoreceptor inner and outer segments. Surprisingly, we observed no effect of vitamin K on the age-dependent loss of photoreceptor cells, interneurons or ganglion cells. These data suggest a role for vitamin K in maintaining the aging retina and suggest that the sparing effect of vitamin K does not reflect the survival-promoting (anti-apoptotic) activities of vitamin K-dependent proteins.

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“…105 In the rat Sertoli and Leydig cells, GAS6 is expressed. Vitamin K influences testicular somatic cells in vitro, but in vivo data are unknown.…”

Section: Influences Of Vitamin K On Cell Growthmentioning

confidence: 99%

Observations on Possible Effects of Daily Vitamin K Replacement, Especially Upon Warfarin Therapy

Bern

2004

J Parenter Enteral Nutr

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Daily parenteral vitamin K supplement is now recommended by the U.S. Food and Drug Administration (FDA) for patients receiving IV hyperalimentation. This is considered as preferable to the previous recommendations of weekly parenteral or oral supplement, or as in some cases no supplement at all. Supplemental vitamin K1 will ensure adequate supplies for hepatic saturation and thus the production of clotting factors II, VII, IX, and X, plus the anticoagulants protein C, protein S, and protein Z. But this is not the entire story. This recommended supplement will affect other physiologic systems that also use vitamin K-dependent gamma-carboxylation. Vitamin K is not 1 molecule but rather 2 natural substances, vitamin K1 and K2, and the synthetic K3's. It is not understood, what, if any, effect may occur because of the saturation or competition from the vitamin K1 upon the functioning of vitamins K2 and the derivatives of K3 in vivo upon bone mineralization, cell growth, and blood vessel health, all known to be influenced by the vitamins K. There are probably other physiologic systems yet to be studied relative to vitamins K and gamma-carboxylation. This review also considers the available research upon warfarin when given to patients receiving hyperalimentation and what effects the vitamin K supplements may have. Because studies to date have not controlled for vitamin K intake, consideration is given to whether one should expect any change in previously reported outcomes when using low-dose warfarin for prophylaxis against central vein thrombosis. Also considered are possible positive or negative effects that chronic warfarin therapy may have upon the other vitamin K-dependent systems under discussion. This review offers a platform for further discussion and derived clinical research provoked by this new FDA recommendation.

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Gas6 Binding to Photoreceptor Outer Segments Requires γ-Carboxyglutamic Acid (Gla) and Ca2+ and is Required for OS Phagocytosis by RPE Cells in vitro

Cited by 40 publications

References 44 publications

Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Effects of Long-term Vitamin K (Phylloquinone) Intake on Retina Aging

Observations on Possible Effects of Daily Vitamin K Replacement, Especially Upon Warfarin Therapy

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