DIABETES AND RETINOPATHY

By Zahra Javed (BS Biochemistry)

DIABETES AND RETINOPATHY

Abstract

Hyperglycemia has adverse effects on all the cells of the body. It mostly affects the cornea and retina. About 70% of diabetic patients suffer from keratopathy. The modifiable factors are hyperglycemia, blood pressure (BP), plasma lipids, and coagulation factors. DR (diabetic retinopathy) is a micro-vasculopathy and also an inflammatory disease. It is the most common cause of blindness.  It is treated with various types of therapies such as systemic and ocular therapies.

Ø  Keywords: diabetes, retinopathy, cornea, inflammation.

Introduction

Hyperglycemia has toxic effects on almost all the cells in the body. Diabetic retinopathy (DR)is the leading cause of vision loss in older people. It is considered an inflammatory disease. DR causes vascular permeability and leukostasis. Leukostasis is the process in which leukocytes circulating in blood vessels leukocytes stick to cells of the endothelial lining of inflamed vessels, troll, and travel into the tissues(Bhat, Pouliot, Couture, & Vaucher, 2014). Anti-inflammatory drugs like aspirin, meloxicam, and etanercept reduces the leukostasis (Lutty,2013). DR is the 5^th most common cause of preventable blindness (Lee, 2015).

Risk Factors behind the Diabetic Retinopathy  

According to the estimation, out of 285 million people with diabetes mellitus worldwide, approximately one third have signs of the diabetic retina and of these, a further one-third of DR is vision-threatening DR, including diabetic macular edema (DME). Hypertension and hyperglycemia are the risk factors that need to be alleviated for controlling the progression of DR (Lee,2015).Lifestyle factors such as cigarette smoking may also be related to retinopathy risk. The other modifiable factors are blood pressure (BP), plasma lipids, and coagulation factors (Sjolie et al.,1997). The other factors of DR are hypertension, poor glycemic control and increasing duration of diabetes (Smith,2007; Lee, 2015).

Morphological Changes in Diabetic Retina

Diabetic retinopathy is a micro vasculopathy in that the microvasculature leaks serum; increased vascular permeability and capillaries are destroyed in the early stages. Hyperglycemia and mitochondrial and extracellular reactive oxygen species (ROS) are toxic to endothelial cells (ECs), pericytes, and neurons, resulting in their death early in DR. There is accumulating proof that low-grade inflammation underlies the vascular complications of DR(Lutty,2013).

Abnormalities of the coagulation factors, fibrinogen and von Willebrand factor are indicators of endothelial dysfunction and contribute to the capillary closure, tissue hypoxia, and disordered retinal blood flow occurring in diabetic retinopathy (Sjolie et al.,1997).

Fig; Changes in the retina associated with Diabetic Retinopathy (Bhat et al., 2014).

Pathological Mechanism

Development of retinopathy is carried out by different pathways including protein kinase C, polyol pathway, apoptosis of retina, protein kinase C, renin-angiotensin system. Small blood vessels are more susceptible to the excessive accumulation of glucose. The glucose flux via the polyol pathway coverts the glucose into sorbitol and fructose followed by the production of reactive oxygen species. This oxidative stress leads to damage of blood vessels. The retina being the most metabolically active affects highly by oxidative stress (Bhat et al., 2014).

 

Fig; Biochemical pathways involved in the Diabetic Retina (Bhat et al., 2014).

 Diabetes Cause the Vision Loss        

Hyperglycemia affects the eyes badly. In the cornea, it causes keratopathy which includes delayed wound healing, ulcer, and edema. In choroid and retina, it kills the neural and vascular cells.

Once the eye has been exposed to hyperglycemia for long-term, basement membranes cause accumulation of toxic advanced glycosylation end products and cell death has occurred. The retinal and choroid damage from hyperglycemia appears as local inflammation. Vascular endothelial growth factor(VEGF), interleukin (IL-1β), and tumor necrosis factor-alpha (TNF-α) are increased in the local milieu. The nuclear factor–κβ (NK-κβ light-chain–enhancer of activated B cells) is activated by TNF-α, which can up-regulate genes involved in ROS production and inflammation. This causes up-regulation of intracellular adhesion molecule-1 (ICAM-1), which binds activated leukocytes in diabetes. Leukocyte oxidative burst injures endothelial cells so that vascular leakage occurs at these sites. The sites may be repaired by adjacent cells but may also be the site of repeated occlusive events. Since a polymorphonuclear (PMN) leukocytes are so large and rigid in diabetics, it fills the lumen when firmly adherent. If the extracellular matrix is exposed, platelet fibrin thrombi will form, which can signal the end of flow in that vascular segment. This also occurs in the diabetic choriocapillaris(Lutty,2013).

 Fig; chronic exposure of the retina to hyperglycemia in Diabetic Retinopathy (Homme et al., 2018).

Therapy of Diabetic Retinopathy

1.      Systemic Therapies

The progression and development of DR can be reduced by systemic therapies. In type 2 diabetes, intensive glycemic control reduced the progression of DR.In addition to this blood pressure control also reduced the progression of DR.

2.       Ocular Therapies for Diabetic Retinopathy

Specific ocular therapies have evolved from destructive therapy using laser photocoagulation to the targeting of the vascular changes with antibodies against the vascular endothelial growth factor (VEGF).Vitrectomies are used to treat severe diabetic retinopathy with and tractional retinal detachment vitreous hemorrhage (Gardne,2016).

Conclusion

Diabetes is the leading cause of vision loss in older people. It mainly affects the retina and cornea where it causes retinal detachment and inflammation. It causes various morphological changes in the eyes. It can be treated by systemic as well as ocular therapies.

 Author's Details

Zahra Javed
BS Scholar

Department of Biochemistry, GC University, Faisalabad.

Reviewed & Edited by

M.Ahsan ul Haq 1*, Asmara Ahmed 2*

1 M.Phil Scholar,2 BS Scholar

*Department of Biochemistry, GC University, Faisalabad.

 References

Ø  Smith, T. S., Szetu, J., & Bourne, R. R. (2007). The prevalence and severity of diabetic retinopathy, associated risk factors and vision loss in patients registered with type 2 diabetes in Luganville, Vanuatu. British journal of ophthalmology, 91(4), 415-419.

Ø  Sjølie, A. K., Stephenson, J., Aldington, S., Kohner, E., Janka, H., Stevens, L., &Petrou, K. (1997). Retinopathy and vision loss in insulin-dependent diabetes in Europe: the EURODIAB IDDM Complications Study. Ophthalmology, 104(2), 252-260.

Ø  Lutty G. A. (2013). Effects of diabetes on the eye. Investigative ophthalmology & visual science, 54(14), ORSF81–ORSF87. https://doi.org/10.1167/iovs.13-12979

Ø  Lee, R., Wong, T. Y., &Sabanayagam, C. (2015). Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye and vision, 2(1), 1-25.

Ø  Gardner, T. W., & Chew, E. Y. (2016). Future opportunities in diabetic retinopathy research. Current opinion in endocrinology, diabetes, and obesity, 23(2), 91–96. https://doi.org/10.1097/MED.0000000000000238

Ø  Bhat, M., Pouliot, M., Couture, R., & Vaucher, E. (2014). The Kallikrein-Kinin system in diabetic retinopathy. In Progress in Drug Research (Vol. 69). https://doi.org/10.1007/978-3-319-06683-7_5

Ø  Homme, R. P., Singh, M., Majumder, A., George, A. K., Nair, K., Sandhu, H. S., ...&Tyagi, S. C. (2018). Remodeling of retinal architecture in diabetic retinopathy: disruption of ocular physiology and visual functions by inflammatory gene products and pyroptosis. Frontiers in physiology, 9, 1268.