There are two pathogenic mechanisms in diabetic cataracts….”
Pathophysiology of Diabetic Cataracts
Osmotic effectIn following sequence for Diabetic Cataracts:
increased Glucose level → increased sorbitol via aldose reductase (rapidly ) into cells
• swelling and rupture of cells
• opacification and cataract formation ( acute cataract cortical or subcapsular )
Direct damageIn the following sequence inDiabetic Cataracts:
• increases Glucose level directly interact with lens proteins
• protein aggregation and cataract formation ( chronic nuclear )
Diabetic Cataracts power point presentations :
Screening of Natural Phytoconstituents to combat Diabetic Cataract
- SCREENING OF NATURAL PHYTOCONSTITUENTS TO COMBAT DIABETIC CATARACT Abhinav Temani Rupesh Vishwakarma Dr. Sadhana Sathaye
- Diabetic Cataract Diabetes mellitus type 1 or juvenile diabetes and Diabetes mellitus type 2 or adult-onset diabetes lead to chronic diabetic complications like neuropathy, nephropathy, angiopathy and retinopathy. Hyperglycemia is known to instigate these diabetic complications. With the increased formation of advanced glycation end products (AGE’S). Enhanced activity of aldose reductase (AR). Formation of reactive oxygen species (ROS).
- Rationale behind DIABETIC CATARACT as therapeutic area Cataract is the most common cause of blindness, accounting for 51 % of world blindness, as of 2010. Although the major cause remains to be aging, it is closely related to diabetes as one of its major late complications. Diabetes mellitus is associated with a 5-fold higher prevalence of cataracts. Some 366 million people worldwide are estimated to have diabetes in 2011, and by 2030, some 552 million people, or every one adult in 10, will have diabetes. So will increase the incidence of diabetic complications like cataract. Hence, substances are required to prevent or treat cataractogenesis. RATIONALE BEHIND THE PROJECT
- Rationale behind choosing POLYOL PATHWAY as the target Although diabetic cataract is a consequence of cumulative effects of various metabolic processes linked to hyperglycaemia, increased activity of Aldose Reductase in the polyol pathway has been regarded as the initiator of the disease process For diabetics, maintaining normoglycaemia at all times is not possible. With drugs that decrease blood glucose levels, there is risk of hypoglycaemia. Hence, aldose reductase inhibitors(ARI’s), which keep these complications in check, and work in complete independence to body sugar levels, seem to be an attractive proposition.
- Focus on herbal substances Although many chemical substances showing potent AR inhibition have been reported, only one, epalrestat, is currently marketed . Toxicity, non-specific activity, limited efficacy, and poor pharmacokinetic properties are some of the severe limitations to therapeutic success of chemical substances. Shifting focus to herbal substances thus seems to be a good idea under such circumstances.
- Choosing Psoralen and Sesamin Coumarin derivatives like umbelliferone have already been reported for their AR inhibitory activity and as potential therapeutic agents against long term diabetic complications. The very fact that Psoralen is a coumarin derivative and its structural similarities with umbelliferone made it our subject of interest. Sesamin is already catered to be a nutritional supplement that confers antioxidant and anti-inflammatory effects or possibly being an estrogen receptor modulator and fat burner. The very fact that it is already used as a supplement coupled with its antioxidant activity encouraged us to test it for aldose reductase inhibition and its inhibition of diabetic cataract.
- Rat Eye Lens Pellet Resuspend in buffer Supernatant fraction Ammonium Sulphate centrifugeHomogenized buffer pH 6.6 with beta mercaptanol Preparation of crude Aldose reductase enzyme from Rat lens: AR enzyme inhibitory activity of different concentration of Psoralen & Sesamin was investigated by use of in vitro spectrophotometric analysis. Their anti-cataract activity was investigated by in-vitro cataract induction on goat lens culture. Protein estimation of goat lens culture was subsequently undertaken. Biochemical evaluation of goat lens culture was subsequently undertaken. Antioxidant activity of Psoralen & Sesamin was investigated. METHODS
- IN-VITRO SPECTROPHOTOMETRIC ANALYSIS OF AR INHIBITORY ACTIVITY AR activity and thereby AR inhibition on addition of different concentrations of Psoralen & Sesamin was determined using Continuous Spectrophotometric Rate Determination using a UV spectrophotometer. AR activity was indicated by loss of NADPH absorbancy due to consumption of NADPH in the reaction whereas AR inhibition was indicated by fall in AR activity on addition of drugs. The reaction mixture contained freshly prepared enzyme, varying concentration of Psoralen or Sesamin, 0.067 M buffer (pH 6.2), 0.125 mM NADPH, 400 mM LiSO4 and 45 mM xylose (substrate) in a 1 mL cuvette. Absorbance data was recorded every second for 3 minutes. Quercetin was used as standard inhibitor.The reference blank contained all the substances except the substrate. DMSO was used as control. Different concentrations of Psoralen & Sesamin were prepared with DMSO as solvent and its % inhibition values were recorded ; % inhibition being given by:
- In vitro ANTI CATARACT ACTIVITY OF PSORALEN A total of 36 lenses were divided in the following categories (n = 4 in each category)- Lens opacity was then judged by observing no of squares clearly visible through the lens when placed on a mesh. Each lens was graded for its integrity and degree of opacity and results were recorded. 72 h Cataract Goat Lens Incubation; 37°c
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Diabetic Cataract Surgery