MMP targeting in the battle for vision: Recent developments and future prospects in the treatment of diabetic retinopathy

• Published in: Life sciences (1973) 2019-07, Vol.229, p.149-156
• Main Authors: Drankowska, Justyna, Kos, Michał, Kościuk, Andrzej, Marzęda, Paweł, Boguszewska-Czubara, Anna, Tylus, Magdalena, Święch-Zubilewicz, Anna
• Format: Article
• Language: English
• Subjects: Aging; Aging (natural); Alzheimer's disease; Animals; Arteriosclerosis; Atherosclerosis; Blindness; Complications; Diabetes; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - enzymology; Diabetic Retinopathy - pathology; Extracellular matrix; Extracellular matrix degradation; Gelatinase A; Gelatinase B; Humans; Matrix metalloproteinase; Matrix Metalloproteinase Inhibitors - therapeutic use; Matrix metalloproteinases; Matrix Metalloproteinases - chemistry; MMP inhibitor; Neurodegenerative diseases; Retina; Retinopathy; Stromelysin 2; Target; Tissue inhibitor of metalloproteinases
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.05.038

Matrix metalloproteinases (MMPs) are enzymes capable of degrading nearly all types of extracellular matrix. They perform a wide range of roles in physiological processes, which is the reason for their strict regulation by numerous mechanisms including natural tissue inhibitors of metalloproteinases (TIMP). Research only started to shed light on more troublesome aspects of MMPs function, like cancer progression, Alzheimer's disease, atherosclerosis, ageing. Moreover, their profound role in diabetes is being carefully investigated including one of its most debilitating complications - diabetic retinopathy (DR), the leading cause of acquired blindness worldwide. Traditional treatment of this condition seems to be only mildly satisfactory, which elicited substantial interest in the field of new therapeutic methods including MMP targeting. So far, significant roles of MMP-2 and MMP-9 in the development of retinopathy have been established, with special attention given to the process of blood-retinal barrier impairment. Further exploration revealed MMP-10 and MMP-14 involvement as well as changes in MMP/TIMP ratio. In this review, we provide insight into MMPs role in diabetic retinopathy with a clarification of various mechanisms regulating MMP activity in the light of the recent studies. We conclude with an overview of novel DR therapies targeting MMPs and point to the need of further examination of their usefulness in clinical setting, with an eye towards future research. [Display omitted]