Hyperglycemia may influence ROP through its signifi- cant effect on retinal blood flow [21]. In diabetic rats, reduction of glucose levels resulted in an improvement in retinal blood flow when compared to diabetic rats who remained hyperglycemic [22]. Additionally, hyperglycemia has been shown to increase the formation of diacylglycerol, which in turn increases activation of protein kinase C. Protein kinase C has been shown to have an effect on many different growth factors, such as vascular endothelial growth factor (VEGF), which impacts angiogenesis and vascular permeability [23]. Hyperglycemia, in hypoxic culture conditions, has also been shown to increase VEGF production in retinal Müller cells [24]. Additionally, in an in vitro assay of VEGF production in cultured bovine retinal pigmented epithelial cells, it was shown that those cells that were exposed to a prolonged period of hypergly- cemia had significantly elevated level of VEGF production
Page 4 of 5
when compared to controls [25]. While the factors that lead to the progression of ROP are not well understood, it is possible that the duration of hyperglycemia is a factor in the initiation of ROP, but other factors such as oxygen exposure and genetics have a more critical role in influencing the factors that are involved in the progression of the disease. As such, duration of hyperglycemia could potentially be more of a risk factor for the development of mild (Stage I) or moderate (Stage II) ROP rather than severe (Stage III) ROP.
Hyperglycemia may influence ROP through its signifi- cant effect on retinal blood flow [21]. In diabetic rats, reduction of glucose levels resulted in an improvement in retinal blood flow when compared to diabetic rats who remained hyperglycemic [22]. Additionally, hyperglycemia has been shown to increase the formation of diacylglycerol, which in turn increases activation of protein kinase C. Protein kinase C has been shown to have an effect on many different growth factors, such as vascular endothelial growth factor (VEGF), which impacts angiogenesis and vascular permeability [23]. Hyperglycemia, in hypoxic culture conditions, has also been shown to increase VEGF production in retinal Müller cells [24]. Additionally, in an in vitro assay of VEGF production in cultured bovine retinal pigmented epithelial cells, it was shown that those cells that were exposed to a prolonged period of hypergly- cemia had significantly elevated level of VEGF productionPage 4 of 5when compared to controls [25]. While the factors that lead to the progression of ROP are not well understood, it is possible that the duration of hyperglycemia is a factor in the initiation of ROP, but other factors such as oxygen exposure and genetics have a more critical role in influencing the factors that are involved in the progression of the disease. As such, duration of hyperglycemia could potentially be more of a risk factor for the development of mild (Stage I) or moderate (Stage II) ROP rather than severe (Stage III) ROP.
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