Biochemical scenario behind initiation of diabetic retinopathy in type 2 diabetes mellitus

Purpose: Despite the disease having similar glycemic status and duration microangiopathy in some patients develop within few years whereas it doesn't appear as a health complication in some diabetics for a considerable period. This study is undertaken to assess the hyperglycemia-induced biochemical background behind the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (DM). Methods: Following proper diagnosis, 100 patients of type 2 DM of 10–12 years duration having no DR, and 42 patients of type 2 DM of the same duration and glycemic status as the second group, with mild retinopathy were recruited in the study. Lactic acid, glutamate, malondialdehyde (MDA), nitrate, advanced glycation end-products (AGEs), peripheral blood mononuclear cell reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), and its receptor 2 (VEGFR2) in these two groups were produced in an assay following standard methodology. Results: Biochemical markers of anaerobic glycolysis, lipid peroxidation, AGEs, glutamate concentration, oxidative stress, and expression of VEGF and its VEGFR2 with significantly elevated markings were found in them who developed earliest stage of DR rather than them who had not. Conclusion: Hyperglycemia-induced anomalous glucose metabolism, lipid peroxidation, advanced glycation, glutamate toxicity, and oxidative stress create a background where apoptosis of retinal capillary endothelial cells invite increased expression of VEGF and VEGFR2, these being the crucial factors behind the development of diabetic microangiopathy.

Alteration of timing of secretion of vascular endothelial growth factors is responsible for progression of diabetic retinopathy.

Diabetic retinopathy is one of the most common complications in diabetes mellitus due to persistent hyperglycaemia. Various biochemical mechanisms have been suggested to cause this complication. The authors' present study which included 100 patients of type-2 diabetes mellitus with different stages of diabetic retinopathy and without retinopathy shows that initiation of diabetic retinopathy is associated with increased anaerobic glycolysis and accelerated oxidative stress. Progression of this complication is guided by increased secretion of vascular endothelial growth factors. It is our assumption that increased secretion of vascular endothelial growth factors in early part of this disease e.g. before occurrence of morphological abnormality may modify this complication.

Unilateral loss of vision following snakebite.

A 14- year-old boy presented at the outpatients' department with the complaint of visual loss in the right eye of 1 1/2 months duration. He had the history of snakebite for which he was admitted to hospital. The diminution of vision started next day after snakebite. On examination, he had no perception of light in his right eye. USG B scan showed vitreous haemorrhage in his right eye. He was given IV methylpredinisolone. At follow-up after one month he still had no perception of light in his right eye with the haemorrhage in the vitreous subsided.

Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy.

In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2 (4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P< 0.001).

The efficacy of topical administration of brimonidine to reduce ischaemia in the very early stage of diabetic retinopathy in good controlled type-2 diabetes mellitus.

It is now proved that diabetic micro-angiopathy is caused by ischaemia at the capillary bed of retina due to reduced capillary blood flow in long standing type-2 diabetes mellitus. Deranged metabolic process due to chronic hypoxia at the tissue level produces visual and vascular dysfunction. Brimonidine tartrate, an alpha-2 agonist which is commonly used in glaucoma to protect retinal ganglion cells from pressure related ischaemia induced cell apoptosis, is administered in very early stage of non-proliferative diabetic retinopathy to reduce ischaemia at the capillary bed of retina. Improved visual acuity and decreased micro-aneurysm formation, which indicate elimination of ischaemic stimulus at the tissue level, are seen in long standing type-2 diabetes mellitus.