Inhibition of Experimental Proliferative Vitreoretinopathy with Protein Kinase C Inhibitor (Chelerythrine Chloride) and Melatonin

Abstract

Purpose: To investigate whether a protein kinase C (PKC) inhibitor and melatonin prevent proliferative vitreoretinopathy (PVR). Methods: Twentypigmented rabbits were used in this study. All rabbits except controls received an intravitreal injection of 0.15 ml (75,000 units) of platelet-rich plasma into their left eye. The animals were divided into four groups: group I was treated with intravitreal injection of 0.1 ml (100 µmol/ml) of PKC inhibitor (chelerythrine chloride), group II received 1 ml (4 mg/kg) of intraperitoneal melatonin for 3 days, group III received nothing (blank group), and group IV (control group) received only 0.5 ml of 1% ethanol intraperitoneally for 3 days. Proliferative changes were graded in a masked fashion by indirect ophthalmoscopy for a 15-day follow-up period. The malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite levels were measured in the vitreous humor. Results: The grades of PVR were A and B in group I and II, treated with PKC inhibitor and melatonin, respectively. The PVR grade in the blank group was C-D. The mean MDA level in group I (4.2 ± 0.9 µmol/l) was significantly lower than in the blank group (6.0 ± 1.0 µmol/l; p < 0.05). The mean GSH level in group I (66.3 ± 8.8 µmol/l) was not significantly different from that in the blank group (p > 0.05). The MDA and GSH levels in group II were 3.2 ± 0.7 and 70.1 ± 13.3 µmol/l, respectively. Both these levels were significantly different from those of the blank group (p < 0.05). The NO levels in both treatment groups were significantly lower than in the blank group (p < 0.001). Conclusion: These findings suggest an inhibitory effect of PKC inhibitor and melatonin on PVR. The inhibition of PVR development was associated with lower MDA and NO levels with higher GSH levels in the treatment groups.

Ocular disorders and the utility of animal models in the discovery of melatoninergic drugs with therapeutic potential

“…Moreover, this effect is in agreement with the protective action of melatonin previously observed in other types of damaged RPE cells such as in ischemic and oxidative stress injury [101,114,115]. In addition, proliferative vitreoretinopathy (PVR) development has been inhibited by melatonin treatment in pigmented rabbits previously injected with platelet-rich plasma [116]. This inhibition was due to the antioxidant actions of melatonin [116].…”

“…Myopia Chicken [36] Diabetes Sprague-Dawley rat diabetic induced [21,22] Wistar rat diabetic induced [42] Radiation-induced OD Rabbit [23] Cataracts Sprague-Dawley rat cataracts induced by GSH inhibition [24] UV B irradiation [44] Gamma irradiation [46] Selenite injection [47] Glaucoma Chronic, moderately elevated IOP rat Hypertonic solution microinjection [75] Episcleral veins cauterization [76] Hyaluronic acid injections [79,80] Glaucomatous induced CS rat [83] New Zeeland normotensive rabbit [62,91,92] Laser-induced glaucomatous monkey [86] Chicken [89] Optic nerve transection mouse [82] Uveitis Cat Intravitreal Injections of Bacterial lipopolysaccharide [94,96] Hamster Pig Bovine serum albumin [95] Hypoxia-ischemia Rat and Pig retinal ischemia model [98][99][100] Retinitis pigmentosa (rds/rds) mouse [110] P23H rat [111] Dystrophic rat RCS [112] Retinal detachment Hyaluronic acid-induced retinal detachment mouse [113] Proliferative vitreoretinopathy Pre-injected platelet-rich plasma pigmented rabbit [116] OD: Ocular disorders.…”

Controlling Retinal Pigment Epithelium Injury after Experimental Detachment of the Retina

“…This hormone is a well-known antioxidant and free radical scavenger 35 that protects human RPE cells against ischemic 36 and oxidative stress, 37 and it can reduce cardiac infarct size 38 and the effects of experimental proliferative vitreoretinopathy. 39 These results are usually attained after prolonged treatment 37 or the administration of 4-to 10-mg/kg doses of melatonin, 38,39 whereas much smaller doses (0.05 mg/kg) for just 1 hour suffice to induce RPE dye exclusion.…”

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

“…Most of the existing studies were made many years ago and usually combined an anti-proliferative agent and a corticosteroid (Chen et al, 1992;Hui and Hu, 1999;Pastor et al, 2000;Salah-Eldin et al, 1994;Tung et al, 2001). There is also one study that combined a protein kinase C inhibitor and melatonin in an experimental model of PVR in rabbits, using grades A and B of the original classification of PVR (Er et al, 2006).…”