Inhibition of corneal angiogenesis by ascorbic acid in the rat model

Graefes Arch Clin Exp Ophthalmol. 2007 Oct;245(10):1461-7. doi: 10.1007/s00417-007-0542-4. Epub 2007 Feb 21.

Abstract

Purpose: To evaluate the effect of topically administered ascorbic acid on experimentally induced corneal neovascularization in the rat model.

Materials and 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).

Conclusion: 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.

MeSH terms

  • Administration, Topical
  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Antioxidants / administration & dosage*
  • Ascorbic Acid / administration & dosage*
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / pathology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Hydrogen-Ion Concentration
  • Nitrates / toxicity
  • Potassium Compounds / toxicity
  • Rats
  • Rats, Long-Evans
  • Silver Nitrate / toxicity

Substances

  • Angiogenesis Inhibitors
  • Antioxidants
  • Drug Combinations
  • Nitrates
  • Potassium Compounds
  • Silver Nitrate
  • Ascorbic Acid
  • potassium nitrate