May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Intravitreal CAI Inhibits Neovascularization in a Mouse Model of Choroidal Neovascularization (CNV)
Author Affiliations & Notes
  • S. Palii
    Pharmacology and Therapeutics, University of Florida, Gainesville, FL
  • S. Caballero, Jr.
    Pharmacology and Therapeutics, University of Florida, Gainesville, FL
  • S. Jurczyk
    RFE Pharma, Alachua, FL
  • A. Franklin
    RFE Pharma, Alachua, FL
  • G. Robinson
    RFE Pharma, Alachua, FL
  • G. Shapiro
    RFE Pharma, Alachua, FL
  • M.B. Grant
    Pharmacology and Therapeutics, University of Florida, Gainesville, FL
  • Footnotes
    Commercial Relationships  S. Palii, None; S. Caballero, None; S. Jurczyk, RFE Pharma, E; A. Franklin, RFE Pharma, E; G. Robinson, RFE Pharma, E; G. Shapiro, RFE Pharma, E; M.B. Grant, None.
  • Footnotes
    Support  NIH 5R42EY0114282
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 910. doi:
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      S. Palii, S. Caballero, Jr., S. Jurczyk, A. Franklin, G. Robinson, G. Shapiro, M.B. Grant; Intravitreal CAI Inhibits Neovascularization in a Mouse Model of Choroidal Neovascularization (CNV) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):910.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Neovascular ocular diseases are severe pathological conditions that can eventually cause blindness and affect all age groups. New treatments to complement those approved or in development are needed. We postulated that a possible ocular drug candidate for high local dose administration would be the small molecule anti–cancer clinical drug, carboxyamidotriazole (CAI; RFE Pharma designation RFE–007). Our studies investigated the in vitro anti–proliferative effects and the ocular anti–angiogenic effects from direct local intravitreal administration.

Methods: : We tested the antiproliferative effects of CAI on human microvascular endothelial cells (HMECs) by determining changes in BrdU incorporation. HMECs were seeded in 96–well plates and allowed to recover for 24 hours prior to being placed in reduced serum medium for an additional 24 hours. Cells were then exposed to a range of CAI concentrations (10–8 M; 10–7 M; 10–6; and 10–5 M). The controls were reduced serum media without drug supplementation, vehicle only supplemented media, as well as serum–free media and the BrdU incorporation was measured with an ELISA kit. CNV was induced in mice by laser treatment with Bruch’s membrane rupture. Immediately following lesion induction the mice received an intravitreal injection of CAI and then a second intravitreal injection one week later. Flat mounts of the posterior pole were used for quantitation of lesion size (volume) by confocal microscopy.

Results: : CAI treatment of HMECs decreased BrdU incorporation in a dose dependent manner. At concentrations up to 18 mg/mL, intravitreal CAI showed no toxicity. The efficacy data showed a reduction in CNV lesion size compared to vehicle treated animals with the injection of 18 mg/mL CAI, the highest drug concentration, significantly decreasing CNV lesion volumes (P = 0.009) compared to 8 mg/ml.

Conclusions: : CAI demonstrates dose dependent inhibition of endothelial cell proliferation and dose dependent reduction in CNV lesion size following laser rupture of the Bruch’s membrane. With the current established data to support CAI as an ocular clinical candidate drug, these studies further support the development of high local concentration–low systemic dose dosage forms of CAI for the treatment of human proliferative retinopathies.

Keywords: choroid: neovascularization • pharmacology • drug toxicity/drug effects 

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