Calcitriol Is a Potent Inhibitor of Retinal Neovascularization

Albert, Daniel M.; Scheef, Elizabeth A.; Wang, Shoujian; Mehraein, Farideh; Darjatmoko, Soesiawati R.; Sorenson, Christine M.; Sheibani, Nader

doi:10.1167/iovs.06-1210

Cited by 148 publications

(156 citation statements)

References 35 publications

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“…For in vivo pharmacokinetic studies in male, C57BL/6 mice (8 wk old), doses of either 0 or 2.5 g/kg (or 0.05 g/mouse or 120 pmol) 1,25(OH) 2D3, dissolved in sterile corn oil (5 l/g), were given ip on days 0, 2, 4, and 8 at 9 AM. The dose was based on a series of published reports, with doses ranging from 0.1 to 5 g/mouse or 0.25 to 5 g/kg for ip or oral administration, daily or every other day in mice (1,2,27,37,39,42,47,55). In humans, doses of 1,25(OH) 2D3 (0.5 g/kg or 38 g) furnished a similar clearance and exposure with minimal toxicity when used intermittently (8,38).…”

Section: Methodsmentioning

confidence: 99%

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Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Chow

Quach

Vieth

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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, its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH) 2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH) 2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH) 2D3 treatment in mice (2.5 g/kg ip, singly or q2d ϫ 4). After a single ip dose, plasma 1,25(OH) 2D3 peaked at ϳ0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH) 2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH) 2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH) 2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH) 2D3. Upon binding of 1,25(OH) 2 D 3 to VDR, the complex undergoes a conformational change and translocates to the nucleus to heterodimerize with the retinoid X receptor (RXR) (4, 32), followed by recruitment of coactivators before binding to vitamin D response elements (VDREs) in promoter regions of VDR-responsive genes to initiate gene transcription (19). One of the physiological roles of 1,25(OH) 2 D 3 is to increase plasma calcium levels through transactivation of the calcium ion channels [transient receptor potential cation channel subfamily V members 5 and 6 (TRPV5 and TRPV6)] in the kidney and intestine (46). It is known that calcium is maintained by the concerted actions in not only the epithelia of the kidney and intestine, but also bone, where turnover is a continuous process involving both resorption of existing bone and deposition of new bone, processes that are stimulated by actions of 1,25(OH) 2 D 3 and the parathyroid hormone, PTH (28, 30).The level of 1,25(OH) 2 D 3 in plasma is tightly controlled by two major cytochrome enzymes in the kidney, CYP27B1 or 1␣-hydroxylase, which converts 25(OH)D 3 to 1,25(OH) 2 D 3 , and CYP24A1, the catabolic enzyme that degrades 25(OH)D 3 and 1,25(OH) 2 D 3 to 24,25(OH) 2 D 3 and 1,24,25(OH) 3 D 3 , respectively (23). CYP24A1 is present in tissues that express VDR (3) and serves as a biomarker for VDR activation. When 1,25(OH) 2 D 3 in plasma is high, CYP24A1 becomes highly induced in the kidn...

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Section: Methodsmentioning

confidence: 99%

“…The level of 1,25(OH) 2 D 3 in plasma is tightly controlled by two major cytochrome enzymes in the kidney, CYP27B1 or 1␣-hydroxylase, which converts 25(OH)D 3 to 1,25(OH) 2 (23). CYP24A1 is present in tissues that express VDR (3) and serves as a biomarker for VDR activation.…”

mentioning

confidence: 99%

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Chow

Quach

Vieth

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…The anti-angiogenic properties of calcitriol (1,25-dihydroxyvitamin D3), has been studied in the mouse model and it has been mentioned as a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component like ROP. 14,15,21 How calcitriol affects angiogenesis has been unclear.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency and morbidity among preterm infants in a developing country

Srinivasan

Chandramathi

Prabhu

et al. 2017

Int J Contemp Pediatr

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INTRODUCTIONAlthough there is no consensus on optimum levels of serum vitamin D levels, vitamin D deficiency is defined as a 25-hydroxy vitamin D level of less than 20 ng per millilitre (50 nmol per litre). [1][2][3][4] No specific definition exists for preterm infants. With the use of such definitions, it has been estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency. [5][6][7] High prevalence of physiologically significant hypovitaminosis D among pregnant women and their term newborns have been reported in India. 8 The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), exerts its bio-logical actions by binding to a nuclear receptor, the vitamin D receptor (VDR) and these are present in almost every organ system in the body. It is speculated that there is a physiologic role for vitamin D and its metabolites in general health. 9,12,13 The awareness of a role for vitamin D in the regulation of immune responses was triggered by the discovery of VDRs in almost all immune cells of the innate and adaptive immune system. 10 Moreover, immune signals can regulate expression levels of the VDR and the enzymes involved in vitamin D metabolism. 11The VDRs and vitamin D metabolizing enzymes have also been identified in both the vasculature and the heart ABSTRACT Background: The association of serum vitamin D levels to clinical outcome in VLBW infants has not been studied. Our objective was to measure the cord blood levels, and the dose response for two doses of vitamin D in preterm infants and correlate the relationship of vitamin D levels to the clinical outcome. Methods: We prospectively obtained cord blood levels in 80 preterm infants under 34 weeks gestation (mean gestation age 29±2 weeks and BW: 1210±350 gms). Infants were supplemented with 400 IU or 800-1000 IU vitamin D daily. Serun vitamin D levels were obtained at 2 -3 weeks after supplementation and levels were correlated to clinical outcome. Results: The mean cord blood vitamin D level was 12±8.5 ng/ml. Babies who developed sepsis and compared to those who did not develop these morbidities, ROP had vitamin D levels: 13.5±6 (ng/ml) versus 30.5±10 (ng/ml) (p < 0.01) and 15.7±11 (ng/ml) versus 34±18 (ng/ml) (p <0.03) respectively. Supplementation with 400 IU vitamin D resulted in levels of 17±8.6 (ng/ml) and infants given 800-1000 IU vitamin D had levels 46±17(ng/ml) (p <0.001). Conclusions: These data suggest that cord blood vitamin D levels are low in preterm infants and 800-1000 IU vitamin D supplementation is advisable to achieve levels >30 ng/ml. Infants with low levels of vitamin D have higher incidence of sepsis, and ROP.

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“…The anti-angiogenic properties of calcitriol (1,25dihydroxyvitamin D3), has been studied in the mouse model and it has been mentioned as a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component like ROP. [9,10,14] How calcitriol affects angiogenesis has been unclear.…”

Section: Discussionmentioning

confidence: 99%

A Study of Vitamin D Level in Newborn with Special Reference to Correlation with Gestational Age, Morbidity and Maternal Vitamin D Level

Shah¹,

Gosai²,

Ladumor³

2017

AIMDR

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Background: Recently the high prevalence of vitamin D level deficiency in general population. Pregnancy and preterm deliveries are known as risk Factors for vitamin d deficiency.. In the study we aimed to compare vitamin D level in term and preterm newborn mother pair. Methods: We prospectively collected vitamin D blood level in term and preterm newborn with their mother's vitamin D level in neonatal ICU at tertiary health care centre. Results: Total 80 newborn mother pair was recruited in study, including 44 preterm (55%) and 36 term (45%) newborns In total 41.9% and 55.9% of preterm and term newborn had vitamin D deficiency, respectively and 47.6% & 32.5% of preterm and term newborn had vitamin D insufficiency, respectively. Among all newborns, 48.9% had vitamin D deficiency, although the difference between term and preterm newborn was not statistically significant. Based on findings, serum vitamin D levels in mother and newborns were significantly correlated (p<0.001). The Data suggest that preterm & term newborn with vitamin D deficiency have higher incidence of ROP & sepsis respectively as compared to others (p<0.001). Conclusion: According to present study, vitamin D level in mother and newborn were significantly correlated and vitamin D level deficiency in preterm and term newborn is associated with higher chances of development of ROP and early onset septicemia respectively, there is no significant correlation between gestational age and vitamin D level in newborn mother pair.

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Calcitriol Is a Potent Inhibitor of Retinal Neovascularization

Abstract: These data suggest calcitriol is a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component.

Cited by 148 publications

References 35 publications

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Vitamin D deficiency and morbidity among preterm infants in a developing country

A Study of Vitamin D Level in Newborn with Special Reference to Correlation with Gestational Age, Morbidity and Maternal Vitamin D Level

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Calcitriol Is a Potent Inhibitor of Retinal Neovascularization

Abstract: These data suggest calcitriol is a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component.

Cited by 148 publications

References 35 publications

Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3treatment in mice

Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3treatment in mice

Vitamin D deficiency and morbidity among preterm infants in a developing country

A Study of Vitamin D Level in Newborn with Special Reference to Correlation with Gestational Age, Morbidity and Maternal Vitamin D Level

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Resources

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Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice

Temporal changes in tissue 1α,25-dihydroxyvitamin D₃, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)₂D₃treatment in mice