Inhibition of corneal angiogenesis by ascorbic acid in the rat model.
OBJECTIVE
To evaluate the effect of topically administered ascorbic acid on experimentally induced corneal neovascularization in the rat model.


METHODS
Corneal chemical cauterization of 72 eyes in Long-Evans male rats was performed using silver nitrate/potassium nitrate sticks. Nine groups of eight eyes were used to evaluate eight concentrations of ascorbic acid with one group of eight eyes serving as a control. Topical instillation of 100 mg/ml non-pH-neutralized ascorbic acid was performed in one group while the remaining seven groups were evaluated using pH-neutralized ascorbic acid in concentrations of 100 mg/ml, 50 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, 500 microg/ml, and 250 microg/ml.


RESULTS
The percentage of corneal neovascularization and burn stimulus score was determined for all the eyes. The means of percent of corneal neovascularization in ascorbic acid 100 mg/ml (non-neutralized), 100 mg/ml, 50 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, 500 microg/ml, 250 microg/ml, and control group were 17.50 +/- 12.80 (p = 0.001), 17.00 +/- 19.30 (p = 0.001), 15.25 +/- 13.26 (p = 0.001), 17.62 +/- 11.89 (p = 0.001), 28.87 +/- 23.08 (p = 0.001), 29.62 +/- 16.91 (p = 0.001), 60.12 +/- 8.50 (p = 0.04), 65.62 +/- 2.26 (p = 0.185), and 68.25 +/- 4.06, respectively (Tables 1 and 2). All animals had a burn score of 2+ or higher (Table 1).


CONCLUSIONS
Ascorbic acid applied in a topical solution appears to inhibit corneal neovascularization in the rat model of inflammatory neovascularization in concentrations in a dose-dependent manner. The optimal dose-effect relation was in our model found in concentrations between 1 mg and 500 microg/ml. At concentrations below 500 microg/ml there was no statistically significant inhibition in the degree of corneal neovascularization compared to control.
Peyman
Gholam A
GA
Department of Ophthalmology, University of Arizona, Arizona Health Sciences Center, 655 N. Alvernon Way, Suite 108, Tucson, AZ 85711, USA. ccole@eyes.arizona.edu
Kivilcim
Muhamet
M
Morales
Ana Munoz
AM
DellaCroce
John T
JT
Conway
Mandi D
MD
D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006863:Hydrogen-Ion Concentration; D009566:Nitrates / Q000633:toxicity; D017680:Potassium Compounds / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D012835:Silver Nitrate / Q000633:toxicity
D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D004338:Drug Combinations; D009566:Nitrates; D017680:Potassium Compounds; D012835:Silver Nitrate; D001205:Ascorbic Acid; C023844:potassium nitrate