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Abstract: TH-PO1114

Expression of MMPS and TIMPS Is Differentially Regulated in Cataract Tissue of Patients with CKD and Diabetes Mellitus (DM) or Both

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials


  • Chong, Calum Wai Kit, Prince of Wales Hospital, Bellevue Hill, New South Wales, Australia
  • Coroneo, Minas Theodore, UNSW, Randwick, New South Wales, Australia
  • Francis, Ian C., Prince of Wales hospital, Randwick, New South Wales, Australia
  • Endre, Zoltan H., Prince of Wales Hospital, Bellevue Hill, New South Wales, Australia
  • Erlich, Jonathan H., UNSW, Randwick, New South Wales, Australia

Cataract is a common preventable cause of blindness particularly amongst diabetics and recent reports suggest an increased incidence in patients with CKD. Matrix metalloproteinases MMPS and their regulators, including tissue inhibitors of MMPS (TIMPS) are variably expressed in lens tissue and may play a role in the genesis of cataract formation. This may result from direct modulation of extracellular matrix or be secondary to cell cycle events or other pathways


We prospectively evaluated 270 patients (age range, 46-93 years; mean, 71 years) who had phacoemulsification cataract surgery with intraocular lens implantation. Cataracts were graded at time of surgery, noting the presence of renal impairment (eGFR<60ml/min), type 2 diabetes mellitus and use of hypolipidemic drugs. For analysis, subjects were categorized according to presence of absence of diabetes mellitus and the presence or absence of CKD. mRNA was extracted from 123 patients, and real time PCR performed for MMPs 1,2,3,9,14 and 15 and TIMPS 1,2,3 and 4. All samples were corrected for the housekeeper gene 18S


Age and CKD but not DM were associated with higher grade cataracts. MMPs 1,3,14 and TIMPS 1,2, and 3 were readily quantifiable by RT PCR. Only low levels of MMP 2 and 9 were observed and could only be quantified as present or absent. MMP15 and TIMP 4 were not detected.
Non-diabetic patients with CKD EGFR < 60 ml/ml had relatively increased expression of MMP1,3,14 and TIMPs 1,2, and 3. There were no detectable differences in MMP 2 and 9. The presence of DM eliminated many differences, with higher levels of MMP 14 and TIMPs 2 and 3 in patients without CKD compared to those with CKD and DM. Hypolipidemic agents modified MMP and TIMP expression in patients with eGFR> 60 ml/min but not CKD. In non-diabetic patients, the product of TIMP 1 or 2 and MMP-3 alone were highly predictive of renal impairment with ROCs of 0.88 and 0.89 respectively. In patients with DM and CKD only TIMP-2 x MMP3 was predictive of CKD with an AUC of 0.74


CKD, diabetes and hypolipidemic agents differentially regulate the expression of MMPS and TIMPs in cataracts. These regulators may be important in the pathogenesis and relevant to potential therapeutic interventions for slowing cataract formation


  • Clinical Revenue Support