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1. Role of Aldose Reductase in Diabetic Retinopathy Presented to : Dr. Shagufta Naz Roll no: Class: MS-I Department of Zoology 2. Aldose Reductase In enzymology, aldose…
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  • 1. Role of Aldose Reductase in Diabetic Retinopathy Presented to : Dr. Shagufta Naz Roll no: Class: MS-I Department of Zoology
  • 2. Aldose Reductase In enzymology, aldose reductase (or aldehyde reductase) is a cytosolic NADPH- dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides. It is primarily known for catalyzing the reduction of glucose to sorbitol, the first step in polyol pathway of glucose metabolism. https://en.wikipedia.org/wiki/Aldose_reducta se
  • 3. Pathway  Cells use glucose for energy; however, unused glucose enters the polyol pathway when aldose reductase reduces it to sorbitol.  The reduction of glucose to sorbitol(a six carbon sugar alcohol obtained by the reduction of the aldehyde group of glucose) is accompanied by the oxidation of NADPH to NADP+.
  • 4. Pathway Then sorbitol is oxidized to fructose by the enzyme sorbitol dehydrogenase(SDH) The oxidation of sorbitol to fructose is paralleled by the reduction of NAD+ to NADH. Then after the enzyme called HEXOKINASE can return the fructose molecule to glycolytic pathway by phosphorylating to form FRUCTOSE- 6-PHOSPHATE.
  • 5. Pathway
  • 6. RING FORM REPRESENTATION
  • 7. PATHOLOGY In a hyperglycemic state, o the affinity of aldose reductase for glucose rises. o causing much sorbitol to accumulate, and using much more NADPH. o leaving less NADPH for other processes of cellular metabolism. Deficiency of NADPH results in less production of nitric oxide which is one of the important vasodilators in blood vessel.
  • 8. Hyperglycemia-induced polyol pathway hyperactivity has an important role in the etiology of late-onset diabetic complications. Once sorbitol has been produced, it does not easily diffuse across cell membranes; this intracellular accumulation of sorbitol may be a factor in the etiology of diabetic complications. Polyol pathway and Diabetes mellitus
  • 9.  Some of the complications include neuropathy, retinopathy, nephropathy, keratopathy, cataract-formation, possibly infection and atherosclerosis.  The inhibition of aldose reductase (AR), a rate-limiting enzyme of the pathway, could become a key element in the prevention and reversal of diabetic complications. COMPLICATIONS
  • 10. Diabetic Retinopathy
  • 11. Diabetes is the major cause of blindness in adults ages 20-74. Diabetic Retinopathy is the largest example of diabetic eye disease. Up to 24,000 Americans lose their sight yearly due to diabetic retinopathy. Facts About Diabetic Retinopathy
  • 12. Four Stages of Diabetic Retinopathy  Mild Nonproliferative Retinopathy  Moderate Nonproliferative Retinopathy  Severe Nonproliferative Retinopathy  Proliferative Retinopathy (National Eye Institute, 2006)
  • 13. Mild Nonproliferative Retinopathy Microaneurysms are the first occurrences of diabetic retinopathy. This happens when the tiny blood vessels of the retina begin to swell. http://www.slideshare.net/drmathewjohn/dia betic-microvascular-complications-2222895
  • 14. Moderate Nonproliferative Retinopathy This is a progressive eye disease and damage to the blood vessels grows. The blood vessels become blocked. http://www.slideshare.net/sushantagarwal98 /diabetic-retinopathyppt
  • 15. Severe Nonproliferative Retinopathy Blood supply is blocked causing the eye to signal the need for new blood vessels. Parts of the retina are deprived of blood and nourishment. http://www.slideshare.net//diabetic-retinopathyppt
  • 16. Proliferative Retinopathy The retina sends signals so new blood vessels are created. These blood vessels are abnormal and more likely to hemorrhage due to the thin walls of the vessel. The walls of these vessels are weak and soon begin to hemorrhage. http://www.drcarmelinagordon.com/conditio ns/diabetic
  • 17. Cotton wool spots Cotton wool spots are an abnormal finding on fundoscopic exam of the retina of the eye. They appear as fluffy white patches on the retina. They are caused by damage to nerve fibers and are a result of accumulations of axoplasmic material within the nerve fiber layer. Cotton wool spots http://www.slideshare.net/wurity/retinal- lesions-pathophysiology
  • 18. In the latest stage of diabetic retinopathy, vision loss is characterized by blurriness, spots, and sometimes blindness. (National Eye Institute, 2003)
  • 19. Functional Implications  Difficulty with fine details  Visual fluctuations  Seeing rippled images  Blurred, hazy or double vision  Some loss of field vision  Difficulty seeing at night or in low light  Sensitivity to light or glare  Trouble focusing images
  • 20. Treatment  Patient Education It is NOT inevitable. Diabetic Retinopathy has few symptoms but can be treated if diagnosed early.  Controlling blood sugar  Laser photocoagulation---laser beams seal vessels and stop new blood vessel growth  Vitrectomy---removes blood and scar tissue to allow light refraction (Juvenile Diabetes Research Foundation International, 2007)
  • 21. Thank You!
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