Author(s):
1. Dragan Vukovic, Specijalna bolnica za oftalmologiju , Serbia

Abstract:
Medical profession used to awaits the appearance of retinal vascular changes before establishing the diagnosis of diabetic retinopathy (DR). Modern understanding of DR recognizes that the visible vascular changes are the result of a long process of biochemical derangement [1]. The cellular and biochemical processes from diabetes cause dysfunction in retinal neurons, glia,and vascular cells, resulting in capillary loss and subsequently hypoxia, which causes production of vascular endothelial growth factor -VEGF(2). Diabetes through hyperglycemia triggers increase in superoxide production from mitochondria. Superoxide inhibits GAPDH, causing accumulation of glycolysis metabolites. One central consequence is glycation of proteins (AGE), with myriad downstream effects including extracellular matrix alteration, infl ammation, vascular occlusion, cytokine production, and cell death(2). Glycosylated proteins can rearrange and dehydrate further to produce brown and fl uorescent pigments,which also act as cross-links between proteins ( 3 ). These oxidized,dehydrated, cross-linked protein compounds are irreversibly altered and are collectively termed advanced glycation end products (AGE) ( 4 ). The glycated precursors of AGE have pathological effects by altering protein structure and function within cells, as well as altering extracellular matrix (ECM) components and ECM interactions with cell receptors such as integrins [ 5 ]. The more complex interlinked AGE can also make long-term alterations to the function of long-lived structural proteins in the ECM, in particular collagen, resulting in a chronic functional change and creating a depot of pathological signaling at RAGE ( 4 ). Collagen cross-linking also increases vascular stiffness and provides a molecular link between diabetes and hypertension ( 6 , 7). Many studies demonstrate that the neural retina may be affected by diabetes before vascular changes appear( 8 ). Neural degeneration from diabetes results in release of vascular permeability factors which lead to damage to retinal capillary endothelium and pericytes causing breakdown in the integrity of blood-retina barrier leading to the accumulation of macrophages and damage to retinal neurons. That is quite obvious that derangements in physiology predate the visible histopathology.(2).We can understand that venous dilatation, perhaps the earliest funduscopic change,is a physiologic adaptation to the altered physiology of insufficient oxygen supply called hypoxia. Apoptosis of capillary pericytes which leads to microaneurysms, is a physiologic adaptation to lost of capillaries and ischemia. At advanced stages, severe ischemia results in high levels of VEGF and abnormal new vessel proliferation. We can realize the limitations of these concepts and develop new methods to assess ocular biochemistry and physiology,so as to diagnose diabetic retinopathy in the stage of physiopathology and not await the more advanced stages of clinically evident histopathology. The earlier diagnosis afforded by this approach will enable intervention at an earlier stage in the natural history of disease when abnormalities are more likely to be reversible, and disease progression can more effectively be mitigated.(2).

Key words:
diabetes,retinal vascular changes,neural degeneration,ocular biochemistry and physiology

Thematic field:
Retina

Date of abstract submission:
23.04.2017.

Conference:
Drugi kongres oftalmologa Republike Srpske sa međunarodnim učešćem