EXPRESSION OF MMPS AND TIMPS ARE DIFFERENTIALLY REGULATED IN CATARACT TISSUE OF PATIENTS WITH CKD AND DIABETES OR BOTH

C CHONG1, I FRANCIS1, Z ENDRE1, M CORONEO1, J ERLICH1
1Renal Research Laboratory, Department of Nephrology, and Department of Opthalmology Prince of Wales Hospital and Prince of Wales Clinical School, Faculty of Medicine, UNSW Sydney, Randwick, Australia

Aim: To investigate the effect of diabetes and CKD on the expression of MMPs and TIMPs from patients undergoing routine cataract surgery.
Background: Cataract is common preventable cause of blindness. It is common amongst patients with diabetes with some recent reports suggesting an increased incidence in patients with chronic kidney disease (CKD). Matrix metalloproteinases MMPs and their inhibitors tissue inhibitors of MMPs (TIMPs) are variably expressed in lens tissue and have been suggested to play a role in the genesis of cataract formation.
Methods: This prospective study comprised 123 patients (age range, 46-93 years; mean, 71 years) who had phacoemulsification cataract surgery with intraocular lens implantation. Patients were categorised according to presence or absence of a diagnosis of diabetes mellitus and the presence or absence of CKD. mRNA was extracted, and real time PCR (RT-PCR) performed for MMPs 1,2,3,9,14 and 15 and TIMPs 1,2,3 and 4. All samples were corrected for the housekeeping gene 18S.
Results: MMPs 1,3,14 and TIMPs 1,2,3 were readily quantifiable by RT-PCR. Levels of MMP2 and 9 were low and could only be detected as present or not. MMP15 and TIMP 4 were not detectable. Non-diabetic patients with CKD EGFR < 60 ml/ml had relatively increased expression of MMPs 1,3,14 and TIMPs 1,2,3. There were no detectable differences in MMP2 and 9. The presence of DMII abrogated many of these differences with MMPs 1,3 and 14 and TIMPs 2 and 3 being higher in patients without CKD compared to the with CKD and DMII.
Conclusion: CKD and diabetes differentially regulate the expression of MMPs and TIMPs in cataracts and this may be important in the pathogenesis of the cataracts.


Biography:
Senior Lecturer in Medicine, Prince of Wales Clinical School, UNSW

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