Diabetic retinopathy

Role of Aldose Reductase in Diabetic RetinopathyPresented to : Dr. Shagufta NazRoll no:Class: MS-IDepartment of Zoology

Aldose ReductaseInenzymology,aldose reductase(oraldehyde reductase) is a cytosolic NADPH-dependentoxidoreductasethat catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides. It is primarily known for catalyzing the reduction ofglucosetosorbitol, the first step inpolyol pathway of glucose metabolism.

https://en.wikipedia.org/wiki/Aldose_reductase

PathwayCells 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+.

PathwayThen 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.

Pathway

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RING FORM REPRESENTATION

PATHOLOGYIn a hyperglycemic state,the affinity of aldose reductase for glucose rises.causing much sorbitol to accumulate, and using much more NADPH.

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.

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

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

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Diabetic Retinopathy

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

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Four Stages of Diabetic RetinopathyMild Nonproliferative Retinopathy

Moderate Nonproliferative Retinopathy

Severe Nonproliferative Retinopathy

Proliferative Retinopathy(National Eye Institute, 2006)

Mild Nonproliferative RetinopathyMicroaneurysms 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/diabetic-microvascular-complications-2222895

Moderate Nonproliferative RetinopathyThis is a progressive eye disease and damage to the blood vessels grows. The blood vessels become blocked.

http://www.slideshare.net/sushantagarwal98/diabetic-retinopathyppt

Severe Nonproliferative RetinopathyBlood 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

Proliferative RetinopathyThe 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/conditions/diabetic

Cotton wool spotsCotton wool spotsare 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 spotshttp://www.slideshare.net/wurity/retinal-lesions-pathophysiology

In the latest stage of diabetic retinopathy, vision loss is characterized by blurriness, spots, and sometimes blindness.(National Eye Institute, 2003)

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Functional ImplicationsDifficulty with fine detailsVisual fluctuationsSeeing rippled imagesBlurred, hazy or double visionSome loss of field visionDifficulty seeing at night or in low lightSensitivity to light or glareTrouble focusing images

TreatmentPatient 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)

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