Calcitriol is a potent inhibitor of retinal neovascularization

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

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

PURPOSE. Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D 3) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro. METHODS. The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro. RESULTS. Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis. CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)2327-2334
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Retinal Neovascularization
Calcitriol
Endothelial Cells
Morphogenesis
Cell Proliferation
Cell Movement
Vascular Endothelial Growth Factor A
Oxygen
Eye Diseases
Basement Membrane
Vitamin D
Western Blotting
Body Weight

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Albert, D., Scheef, E. A., Wang, S., Mehraein, F., Darjatmoko, S. R., Sorenson, C. M., & Sheibani, N. (2007). Calcitriol is a potent inhibitor of retinal neovascularization. Investigative Ophthalmology and Visual Science, 48(5), 2327-2334. https://doi.org/10.1167/iovs.06-1210

Calcitriol is a potent inhibitor of retinal neovascularization. / Albert, Daniel; Scheef, Elizabeth A.; Wang, Shoujian; Mehraein, Farideh; Darjatmoko, Soesiawati R.; Sorenson, Christine M.; Sheibani, Nader.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 5, 01.05.2007, p. 2327-2334.

Research output: Contribution to journalArticle

Albert, D, Scheef, EA, Wang, S, Mehraein, F, Darjatmoko, SR, Sorenson, CM & Sheibani, N 2007, 'Calcitriol is a potent inhibitor of retinal neovascularization', Investigative Ophthalmology and Visual Science, vol. 48, no. 5, pp. 2327-2334. https://doi.org/10.1167/iovs.06-1210
Albert, Daniel ; Scheef, Elizabeth A. ; Wang, Shoujian ; Mehraein, Farideh ; Darjatmoko, Soesiawati R. ; Sorenson, Christine M. ; Sheibani, Nader. / Calcitriol is a potent inhibitor of retinal neovascularization. In: Investigative Ophthalmology and Visual Science. 2007 ; Vol. 48, No. 5. pp. 2327-2334.
@article{694420482d45403c9ec21ee68ae82623,
title = "Calcitriol is a potent inhibitor of retinal neovascularization",
abstract = "PURPOSE. Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D 3) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro. METHODS. The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro. RESULTS. Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis. CONCLUSIONS. 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.",
author = "Daniel Albert and Scheef, {Elizabeth A.} and Shoujian Wang and Farideh Mehraein and Darjatmoko, {Soesiawati R.} and Sorenson, {Christine M.} and Nader Sheibani",
year = "2007",
month = "5",
day = "1",
doi = "10.1167/iovs.06-1210",
language = "English (US)",
volume = "48",
pages = "2327--2334",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "5",

}

TY - JOUR

T1 - Calcitriol is a potent inhibitor of retinal neovascularization

AU - Albert, Daniel

AU - Scheef, Elizabeth A.

AU - Wang, Shoujian

AU - Mehraein, Farideh

AU - Darjatmoko, Soesiawati R.

AU - Sorenson, Christine M.

AU - Sheibani, Nader

PY - 2007/5/1

Y1 - 2007/5/1

N2 - PURPOSE. Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D 3) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro. METHODS. The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro. RESULTS. Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis. CONCLUSIONS. 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.

AB - PURPOSE. Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D 3) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro. METHODS. The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro. RESULTS. Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis. CONCLUSIONS. 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.

UR - http://www.scopus.com/inward/record.url?scp=34250176879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250176879&partnerID=8YFLogxK

U2 - 10.1167/iovs.06-1210

DO - 10.1167/iovs.06-1210

M3 - Article

VL - 48

SP - 2327

EP - 2334

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 5

ER -