As mentioned, oxidative stress is considered one of the major contributors to the development of diabetic retinopathy. The use of antioxidants in animal models of diabetic retinopathy has provided promising results. Prevention studies using two different models of diabetic retinopathy (streptozotocin-induced or experimentally galactosemic rats) have shown that long-term administration of vitamins C and E (10-g/kg and 1-g/kg diet, respectively) ameliorates the development of early signs of retinopathic acellular capillaries and pericyte ghosts in diabetic rats, but not in experimentally galactosemic rats.
40 Vitamin C supplementation decreases the leukostasis and increases iris blood flow perfusion in diabetic rats,
66 suggesting that it has potential in preventing leukostasis, which precedes the development of diabetic retinopathy. However, when vitamins C+E are supplemented with other antioxidants (multiantioxidants: vitamin C 1 g/kg, trolox 500 mg/kg, α-tocopherol acetate 250 mg/kg,
N-acetyl cysteine 200 mg/kg, β-carotene 45 mg/kg, and selenium 0.1 mg/kg of diet), the formation of acellular capillaries and pericyte ghosts is ameliorated in both diabetic rats and experimentally galactosemic rats.
40 This antioxidant mixture also prevents other abnormalities implicated in the development of diabetic retinopathy, including abnormalities in the retinal antioxidant defense mechanism and activation of retinal protein kinase C, nuclear transcriptional factor, and the apoptosis execution enzyme, caspase-3.
67–68 Furthermore, others have shown that administration of green tea, rich in polyphenolic compounds with potent antioxidant activity, to diabetic rodents improves the histopathology characteristic of diabetic retinopathy.
69 Zeaxanthin supplementation in diabetic rodents significantly inhibits oxidative damage and protects the retina from the inflammatory mediators associated with the pathogenesis of diabetic retinopathy.
70 Lutein decreases the total retinal thickness and loss of ganglion cells and protects impairment in the ERGs.
71,72 Curcumin, a polyphenol with potent antioxidant and anti-inflammatory effects, decreases oxidative stress and proinflammatory markers in the retina of diabetic rodents.
73 In addition, curcumin significantly decreases histone acetyl transferase activity and cytokine production, possibly via an epigenetic mechanism,
74 and deacetylation of histone is considered important in the development of diabetic retinopathy.
75 These animal studies have raised the possibility that the natural compounds have the potential to inhibit the development of retinopathy in diabetic patients.