The Protective Effect of Topical Antiglaucoma Eyedrops, Systemic Neuroprotective Drugs and Nutritional Antioxidant Supplements on High Intraocular Pressure Injury in Rat Retina
Date Issued
2012
Date
2012
Author(s)
Chen, Yi-Ing
Abstract
Glaucoma, a group of diseases characterized by progressive optic nerve degeneration, is the leading cause of irreversible blindness worldwide. The initiation of the disease and its progression involve an ischaemic-like insult to the ganglion cell axons. Thus, we use a rat model of retinal ischemia–reperfusion (IR) injury in the present study as an acute model of glaucoma.
The purpose of this study was to evaluate the retinal protective effect of topical brinzolamide (AZ) and timolol (TI)；intravenous (IV) lidocaine (LI) and methylprednisolone (ME)；intraperitonium (IP) minocycline (MI)；nutritional antioxidant supplements antioxidant A (mixed antioxidants with 18 ingredients), antioxidant B (mixed antioxidants with 17 ingredients, without lutein), antioxidant C (mixed antioxidants with 17 ingredients, without bilberry). The study was separated into two parts.
PartⅠ：Adult Sprague-Dawley rats were divided into 7 groups, the normal control (n=6), IR injury (n=6), AZ (n=6), TI (n=6), LI (n=6), ME (n=6) and MI (n=6). In AZ and TI groups, brinzolamide and timolol were administered topically three times a day for 7 days after the IR injury. In LI group, lidocaine bolus (1.5 mg/kg) was IV injected 30 minutes before ischemia and then a constant rate infusion (CRI) with 2 mg/kg/hr was given until 60 minutes after reperfusion. In ME group, methylprednisolone bolus (30 mg/kg) was IV administered twice at 2 minutes before and immediately after ischemia, respectively. In MI group, minocycline at 22 mg/kg was intraperitoneally administered daily for 7 days after the IR injury. Protection of the retina was determined by electroretinogram (ERG) 1 day before and 1, 3, 7 day(s) after the IR injury and by morphometrical histology analysis 7 days after the IR injury. In addition, oxidative stress, the activity of antioxidant enzymes and proteomic analysis were used to investigate the possible mechanisms of the protective effect against IR injury. Our electroretinographic data indicated that topical timolol, methylprednisolone IV and minocycline IP attenuated the effects of retinal ischaemia/reperfusion injury. The retinal histopathology results presented protective effect of topical brinzolamide and lidocaine IV in inner and outer retina. The activity of antioxidant enzymes were higher and the level of oxidative stress was lower in methylprednisolone and minocycline treated groups. The protein expression altered by methylprednisolone include: oxidative stress proteins, glycolysis proteins, immunomodulatary proteins and cytoskeletal proteins.
Part Ⅱ：Adult Sprague-Dawley rats were divided into 5 groups, the normal control (n=6), IR injury (n=6), antioxidant A (n=6), antioxidant B (n=6) and antioxidant C (n=6). The antioxidant A, B, C groups were treated by feeding unknown mixed antioxidants daily for 56 days (28 days before and 28 days after the IR injury). The electroretinography of all groups were assessed at 1 day before and 7, 14, 21, 28, 35, 42, 49, 56 days after feeding unknown mixed antioxidants. In addition, oxidative stress and the activity of antioxidant enzymes were used to investigate the antioxidative effect against the IR injury. After IR injury, both the a- and b-waves in the ERG decreased; however, antioxidant A and C treated groups reduced these effects. The activity of antioxidant enzymes was higher and the level of oxidative stress was lower in antioxidant A and C treated groups.
These findings suggest that timolol, methylprednisolone, minocycline, antioxidant A and antioxidant C possessed good antioxidative activity and protective effect for the retina. Brinzolamide and lidocaine provided protective effect to preserve the thickness of retina, but not in retinal function. Methylprednisolone had anti-oxidation, anti-apoptotic, neovascularization and inflammatory regulation effects proved by proteomic analysis. Based on these investigations, neuroprotective efficacy of treated groups is listed as follows. Drugs：methylprednisolone > minocycline > timolol > lidocaine > brinzolamide. Antioxidants treated: Lutein + bilberry ≥ lutein >> bilberry.
Subjects
glaucoma
retinal ischemia
neuroprotection
antioxidation
Type
thesis
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