ascorbic-acid and Corneal-Neovascularization

Corneal neovascularization is a significant, sight-threatening complication of many ocular surface disorders. Various growth factors and proteinases are involved in corneal neovascularization. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of VEGF and MMPs is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has been demonstrated for reducing VEGF and MMPs secretion by various cells. Moreover, NM can inhibit endothelial cell migration and capillary tube formation. We herein note that topical application of NM is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations in animal models are needed to place NM alongside corneal neovascularization therapeutics.

Topics: Administration, Topical; Animals; Ascorbic Acid; Corneal Neovascularization; Depression, Chemical; Drug Combinations; Humans; Lysine; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Ophthalmic Solutions; Phytotherapy; Plant Extracts; Proline; Tea; Vascular Endothelial Growth Factor A

To determine the efficacy of the topical application of ascorbic acid for the treatment of corneal neovascularization.. Corneal neovascularization was induced in 16 rabbits with a silk suture in the corneal stroma (32 eyes). At 1 week after suturing, 15 rabbits were divided into 3 groups and were treated with topical ascorbic acid at 3 different concentrations: 10 mg/mL (group 1), 1 mg/mL (group 2), and 0.5 mg/mL (group 3). All treatments were added in the right eye twice a day. All left eyes (15 eyes) and both eyes of the 16th rabbit were used as experimental controls and a normal control, respectively. The area of corneal neovascularization was measured using light microscopy. The concentrations of vascular endothelial growth factor and matrix metalloproteinase-9 in the corneal tissue were measured.. The neovascularized area was decreased in the treated groups compared with the control group. There was a significant difference in the neovascularized areas between the control and groups 1 and 2. No significant difference was observed between the control and group 3. The concentration of vascular endothelial growth factor was significantly lower in the treated groups than in the control group, but there was no difference between the treated groups. The concentration of matrix metalloproteinase-9 showed a significant difference between the control and treated groups, but no difference between the treated groups.. Topical administration of ascorbic acid may be useful for the treatment of corneal neovascularization.

Topics: Administration, Topical; Animals; Antioxidants; Ascorbic Acid; Corneal Neovascularization; Disease Models, Animal; Female; Male; Matrix Metalloproteinase 9; Ophthalmic Solutions; Rabbits; Treatment Outcome; Vascular Endothelial Growth Factor A

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

Topics: Administration, Topical; Angiogenesis Inhibitors; Animals; Antioxidants; Ascorbic Acid; Corneal Neovascularization; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Hydrogen-Ion Concentration; Nitrates; Potassium Compounds; Rats; Rats, Long-Evans; Silver Nitrate

To establish an experimental model for sulfur mustard-induced acute and delayed ocular lesions in rabbits.. Rabbit eyes were exposed to sulfur mustard (HD) vapor (370, 420 microg/l) for a period of two minutes. A three months follow-up study was carried out, based on the evaluation of clinical, biochemical and histological parameters.. HD exposure initiated typical clinical symptoms within 2-6 hrs, characterized by eye closure, eyelid swelling, conjunctival hyperemia, corneal erosions and inflammation. The clinical signs were significantly dose-dependent and reached a peak at 24--72 hrs post exposure. Biochemical evaluation of the aqueous humor exhibited an inflammatory reaction and oxidative stress at 4 hrs after exposure, subsiding at 28 hrs after exposure. Histological examination of corneas at 48 hrs revealed epithelial denudation and marked stromal edema, accompanied by cellular infiltration. Epithelial regeneration started after 72 hrs, and recovery was almost completed within 1--2 weeks, depending on the HD dose. A second phase of pathological processes started as early as two weeks post exposure and was characterized by corneal edema, opacity, recurrent erosions and neovascularization. The delayed injuries were found in 25 and 40% of the eyes respectively, and when appearing, were more severe than the initial ones.. The development of HD-induced ocular lesions in rabbits is similar to the lesions described in human casualties. Quantitative analysis of the various clinical parameters emphasizes the contribution of each tissue to the overall toxic picture. Our experimental model is useful for studying the pathological mechanisms of HD-ocular lesions, and may serve for testing potential therapies.

Topics: Acute Disease; Animals; Ascorbic Acid; Cornea; Corneal Edema; Corneal Neovascularization; Corneal Opacity; Dermatologic Agents; Dose-Response Relationship, Drug; Eye Proteins; Female; Glutathione; Models, Animal; Mustard Gas; Rabbits; Time Factors

Topics: Ascorbic Acid; Cornea; Corneal Neovascularization; Vitamins