Abstract
Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.
Highlights
Diabetic retinopathy (DR) is a common microvascular complication associated with diabetes mellitus, which leads to vision impairment and blindness [1]
The anti-angiogenic properties of tocotrienol-rich fraction (TRF) have been attributed to its ability to suppress several signaling pathways, such as Ras-Raf-MEK-ERK and Fyn/HIF-1a pathways, leading to downregulation of vascular endothelial growth factor (VEGF) expression [25]. Considering these beneficial properties of TRF, in this study, we investigated the effect of TRF on retinal morphology and expression of VEGF in a rat model of streptozotocin (STZ)-induced DR
This study demonstrated the protective effect of TRF against DR in STZ-induced diabetic rats
Summary
Diabetic retinopathy (DR) is a common microvascular complication associated with diabetes mellitus, which leads to vision impairment and blindness [1]. Retinal microvascular changes are the characteristic feature of DR; it has been observed that retinal neurodegeneration may appear even ahead of microvascular changes [8]. Diabetic retinal neurodegeneration involves retinal cell apoptosis, leading to thinning of retinal layers and loss of neuronal functions [9]. Hyperglycemia-induced oxidative stress, one of the important mechanisms involved in microvascular complications of diabetes mellitus [10], triggers cellular events that result in activation of various inflammatory cytokines and growth factors. Increased expression of vascular endothelial growth factor (VEGF), an angiogenic protein, is associated with diabetes-induced oxidative stress and neurodegeneration [12,13]
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