Causes and Risk Factors
Diabetes is the increase in blood glucose as a result of inefficient glucose metabolism primarily due to poor insulin production or insulin resistance. Insulin, a hormone that metabolizes glucose so it can be absorbed by the body as glycogen and later used as an energy source, is an important blood sugar regulator. In type 1 diabetes, the body is incapable of producing insulin, where as in Type 2 diabetes, there is a reduced production of insulin and insulin resistance so the body is unable to metabolize glucose efficiently if at all.
Most patients of diabetic retinopathy (DR) have type 2 diabetes. In general, hyperglycaemia causes changes in the flow of blood and increased permeability of blood vessels. The exact mechanism by which diabetes causes DR is still a mystery. However, many experiments have suggested four different mechanisms that cause damage to the small blood vessels in the retina. These include "polyol pathway flux, increased advanced glycation end product (AGE), activation of protein kinase C, and increased hexosamine pathway flux" (Brownlee, 813).
The polyol pathway is not very active with normal glucose levels because aldose reductase has a low affinity for glucose. But during hyperglycaemia, aldose reductase affinity for glucose increases, which catabolizes the glucose to sorbitol also decreasing the NADPH concentration. Because sorbitol does not cross the cell membrane, it was once thought to cause osmotic stress in the bloo vessels. But the sorbitol levels are too low to increase osmotic stress. Low NADPH levels have been linked to a decreased reduction of another molecule called GSH which would actually increase osmotic stress and cause the blood vessels to swell and leak.
The increased AGE alters cell interactions by modifying gene expression, and matrix proteins that ultimately leads to an increase in vascular permeability. The increase in protein kinase C eventually leads to a decrease in vasodilation by reducing the levels of nitric oxide. The hexosamine pathway flux causes changes in gene expression and protein function. (Brownlee, 817) All four of these mechanisms are a result of mitochondrial superoxide overproduction.
The main risk factors for DR include: High blood pressure, pregnancy, smoking, high cholesterol levels, black or hispanic, and poor blood sugar control.