Aldose reductase is an enzyme that catalyzes the reduction of glucose to sorbitol in the polyol pathway. Under hyperglycemic conditions seen in diabetes, increased aldose reductase activity leads to sorbitol accumulation which is implicated in diabetic complications like retinopathy. Diabetic retinopathy progresses through mild, moderate, and severe nonproliferative stages before reaching the proliferative stage where new abnormal blood vessels form that can hemorrhage. It is a leading cause of blindness and its treatment involves controlling blood sugar, laser photocoagulation, and vitrectomy.

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!