Matrix metalloproteinase in diabetic retinopathy

The inflammatory processes in diabetic retinopathy (DR) are executed by leukocytes and their molecules. An important class of leukocyte effector molecules are the matrix metalloproteinases (MMPs), which are used by leukocytes to penetrate sites of inflammation. More than 20 MMPs are counteracted by 4 natural tissue inhibitors of metalloproteinases (TIMPs). By analysis of vitreous fluids of patients with diabetic retinopathy and ophthalmological controls, MMP-9 has been detected as a disease marker of eye inflammations. MMP-9 is a gelatinase and cleaves denatured and not intact collagens. For collagenolysis, one of the collagenases (MMP-1, MMP-8 and MMP-13) need to be present. In DR, MMP-1 levels are increased in the vitreous and may execute collagenolysis. In addition, MMP-9 also cleaves the neuroprotective factor prominin-1/CD133, abundantly present in photoreceptors. The fact that MMP-9 gene knockout mice are resistant to the development of DR suggests MMP-9 inhibition may be beneficial. The techniques to detect various forms of MMPs and the relevance of inhibitors will be discussed.

References

(1) PLoS One (2013) 8: e85857; (2) Progress in Retinal and Eye Research (2014) 43: 76–91; (3) Nature Methods (2013) 10: 211–220.