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Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia.
Invest Ophthalmol Vis Sci. 2002 May; 43(5):1546-57.IO

Abstract

PURPOSE

To evaluate the molecular responses of vascular endothelial growth factor (VEGF) and its receptors to dexamethasone (Dex) and celecoxib (Cel) during hyperoxia and during hyperoxia followed by recovery in room air, in newborn rabbit retinas.

METHODS

Newborn rabbits at 3 days postnatal age (n = 96) received room air or oxygen (80%-100%) for 4 days, during which they were administered saline (Sal), Dex, vehicle (Veh), or Cel (n = 12/treatment group). Six animals from each group were killed immediately after hyperoxia (or room air) and the remainder exposed to room air for 5 days. Retinal mRNA expression of VEGF(121), VEGF(165), VEGF receptor-1 (VEGFR-1, or Flt-1), and VEGFR-2 (or KDR/Flk-1) was determined.

RESULTS

Hyperoxia resulted in increased retinal expression of mRNA of the VEGF splice variants in the groups treated with Sal, Dex, and Veh, whereas a decrease in VEGF(121) was noted in the Cel-treated group. In contrast, retinal Flt-1 receptor mRNA was markedly increased in the Cel-treated group only, whereas retinal VEGFR-2 (KDR/Flk-1) receptor mRNA was suppressed in all the treatment groups. Hyperoxia followed by recovery in room air resulted in a minimal decrease in expression of retinal Flt-1 mRNA in the Sal and Dex groups. Cel treatment abolished its expression.

CONCLUSIONS

The findings of increased retinal expression of VEGF mRNA in the newborn rabbit in response to hyperoxia are most likely due to species differences. Selective targeting of VEGF(121) and Flt-1 mRNA by Cel may represent one regulatory pathway for their anti-inflammatory effects. Further studies are needed to evaluate the therapeutic benefits of cyclooxygenase (COX)-2 inhibitors for the treatment and/or prevention of diseases associated with neovascularization.

Authors+Show Affiliations

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of California, Irvine Medical Center, 101 The City Drive, Building 2 Route 81, Orange, CA 92868, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11980873

Citation

Ozaki, Naomi K., et al. "Regulation of Retinal Vascular Endothelial Growth Factor and Receptors in Rabbits Exposed to Hyperoxia." Investigative Ophthalmology & Visual Science, vol. 43, no. 5, 2002, pp. 1546-57.
Ozaki NK, Beharry KD, Nishihara KC, et al. Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia. Invest Ophthalmol Vis Sci. 2002;43(5):1546-57.
Ozaki, N. K., Beharry, K. D., Nishihara, K. C., Akmal, Y., Ang, J. G., Sheikh, R., & Modanlou, H. D. (2002). Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia. Investigative Ophthalmology & Visual Science, 43(5), 1546-57.
Ozaki NK, et al. Regulation of Retinal Vascular Endothelial Growth Factor and Receptors in Rabbits Exposed to Hyperoxia. Invest Ophthalmol Vis Sci. 2002;43(5):1546-57. PubMed PMID: 11980873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia. AU - Ozaki,Naomi K, AU - Beharry,Kay D, AU - Nishihara,Kenji C, AU - Akmal,Yasir, AU - Ang,Jorge G, AU - Sheikh,Rizwan, AU - Modanlou,Houchang D, PY - 2002/5/1/pubmed PY - 2002/6/4/medline PY - 2002/5/1/entrez SP - 1546 EP - 57 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 43 IS - 5 N2 - PURPOSE: To evaluate the molecular responses of vascular endothelial growth factor (VEGF) and its receptors to dexamethasone (Dex) and celecoxib (Cel) during hyperoxia and during hyperoxia followed by recovery in room air, in newborn rabbit retinas. METHODS: Newborn rabbits at 3 days postnatal age (n = 96) received room air or oxygen (80%-100%) for 4 days, during which they were administered saline (Sal), Dex, vehicle (Veh), or Cel (n = 12/treatment group). Six animals from each group were killed immediately after hyperoxia (or room air) and the remainder exposed to room air for 5 days. Retinal mRNA expression of VEGF(121), VEGF(165), VEGF receptor-1 (VEGFR-1, or Flt-1), and VEGFR-2 (or KDR/Flk-1) was determined. RESULTS: Hyperoxia resulted in increased retinal expression of mRNA of the VEGF splice variants in the groups treated with Sal, Dex, and Veh, whereas a decrease in VEGF(121) was noted in the Cel-treated group. In contrast, retinal Flt-1 receptor mRNA was markedly increased in the Cel-treated group only, whereas retinal VEGFR-2 (KDR/Flk-1) receptor mRNA was suppressed in all the treatment groups. Hyperoxia followed by recovery in room air resulted in a minimal decrease in expression of retinal Flt-1 mRNA in the Sal and Dex groups. Cel treatment abolished its expression. CONCLUSIONS: The findings of increased retinal expression of VEGF mRNA in the newborn rabbit in response to hyperoxia are most likely due to species differences. Selective targeting of VEGF(121) and Flt-1 mRNA by Cel may represent one regulatory pathway for their anti-inflammatory effects. Further studies are needed to evaluate the therapeutic benefits of cyclooxygenase (COX)-2 inhibitors for the treatment and/or prevention of diseases associated with neovascularization. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/11980873/Regulation_of_retinal_vascular_endothelial_growth_factor_and_receptors_in_rabbits_exposed_to_hyperoxia_ L2 - https://iovs.arvojournals.org/article.aspx?volume=43&issue=5&page=1546 DB - PRIME DP - Unbound Medicine ER -