**1. Introduction**

Despite remarkable advances in diagnosis and treatment, diabetic retinopathy (DR), the most frequently occurring complication causing vision loss in working population, is becoming the burning social problem. Two landmark studies have established that hyperglycemia is the principal contributing factor to the development of the disease, though a reasonable portion of diabetic subjects develops this complication in spite of good control of blood sugar [1–3]. In a large densely populated country like India, where strict control of hyperglycemia is far from reality due to lack of clinic adherence, bad economy and illiteracy. Here, principal diet is carbohydrate since childhood. Enormous intracellular glucose in tissues including retina where glucose transport is insulin independent, overwhelms the glycolysis and citric acid cycle owing to gradual deficiency of oxidized cofactors i.e. nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD), thiamine pyrophosphate (TPP), Coenzyme A and lipoate. The essential vitamins, the precursors of these factors could not be provided with only carbohydrates [4]. Unutilized glucose is diverted to anomalous biochemical pathways like sorbitol pathway, and advanced glycation end products formation [5]. Hexose monophosphate shunt (HMP-shunt) or pentose phosphate pathway (PPP) take-up glucose-6-phosphate for its catabolism and produces specialized products like pentose ribose 5-phosphate to make RNA, DNA, and NADPH for reductive synthesis e.g. reduced glutathione peroxidase and fatty acids, the building blocks of lipid structure.

Beside reductive biosynthesis, NADPH carries life-saving roles to counter the damaging effects of oxygen radicals on erythrocytes, cells of lens, cornea and retina. Retina is a tissue where renewal of outer segment of photoreceptors is continuously going on in one side and other side shows light and oxygen induced death of cells as an inevitable phenomenon caused by oxidative stress.

Poorly controlled glycemia and lack of proper metabolism of glucose mainly result in formation and accumulation of advanced glycation end products (AGEs) and reactive oxygen species (ROS) which in turn cause microvascular endothelial cell dysfunction by oxidative modifications of membrane proteins and lipids [6]. Production of advanced lipoxidation end products (ALEs) during peroxidative damage of lipids may be the important source of protein modification by covalent bonding with catalytic site. Circulating AGEs and ALEs exert their detrimental effects through interactions with their cell surface receptor for AGE (RAGE) leading to post receptor activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial cells, mesangial cells and macrophases [7]. Activation and subsequent uncoupling of NADPH oxidase is coupled with increased formation of intracellular reactive oxygen species. Activation of this system also follows the other pathways which suggest increased production of intermediate of faster glycolysis e.g. glycerol 3-phosphate derived inositol triphosphate and diacylglycerol. Inositol triphosphate mediates a transient increase in the level of cytosolic Ca++ which is essential for activation of NADPH oxidase and induction respiratoy burst e.g. generation of large amounts of superoxide anion, hydroxyl anion, and hydrogen peroxide [8].

Diacylglycerol (DAG) induces the translocation of protein kinase C (PKC) into plasma membrane from cytosol, where it catalyzes the phosphorylation of various proteins including the components of NADPH oxidase, and thus activates this system [9].

Beside structural modifications of retinal membrane, AGEs and ALEs invite up regulation of inflammatory mediators and adhesion molecules in capillary beds which cause apoptosis of endothelial cell and breakdown of tight junctions *Role of Lipid, Protein-Derived Toxic Molecules, and Deficiency of Antioxidants… DOI: http://dx.doi.org/10.5772/intechopen.99904*

of blood-retinal barrier [10]. Active vitamin C is ascorbic acid and acts as a donor of reducing equivalents which is capable of reducing compounds as molecular oxygen, nitrate and cytochromes a and c. This ascorbic acid acts as a water soluble antioxidant reduce oxidized tocopherol in lipid membranes [11]. Such vitamin is also required for hydroxylation of amino acids, proline and lysine in the synthesis of collagen [12]. So, deficiency of vitamin C leading to defective collagen synthesis and accumulation of reactive carbonyl compounds due to oxidative stress results in fragility of retinal capillary membranes and enhancement of break-down of inner blood-retinal barrier. In this study we attempted to determine the accompanying role of different lipid derived toxic molecules and deficiency of antioxidant in the pathogenesis of an inflammatory disease, DR.
