| Presentation preference | Invited lecture |
| Title | Tissue inhibitor of metalloproteinase-3 ameliorates diabetes-induced retinal inflammation |
| Purpose | Endogenous tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) has powerful regulatory effects on inflammation and angiogenesis. We investigated the role of TIMP-3 in regulating inflammation in the diabetic retina. |
| Methods | Vitreous samples from patients with proliferative diabetic retinopathy (PDR) and non-diabetic patients were subjected to Western blot analysis. Streptozotocin-treated rats were used as a preclinical diabetic retinopathy (DR) model. Blood-retinal barrier (BRB) breakdown was assessed with fluorescein isothiocyanate-conjugated dextran. Rat retinas, human retinal microvascular endothelial cells (HRMECs) and human retinal Müller glial cells were studied. |
| Results | Intravitreal injection of TIMP-3 attenuated diabetes-induced BRB breakdown. This effect was associated with downregulation of diabetes-induced upregulation of the p65 subunit of NF-KB, intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF). In Müller cell cultures, TIMP-3 significantly attenuated VEGF upregulation induced by high-glucose (HG), the hypoxia mimetic agent cobalt chloride (CoCl2) and TNF-Alpha and attenuated MCP-1 upregulation induced by CoCl2 and TNF-Alpha. TIMP-3 attenuated HG-induced upregulation of phospho-ERK1/2, caspase-3 and the mature form of ADAM17 in Müller cells. TIMP-3 significantly downregulated TNF-Alpha-induced upregulation of ICAM-1 and VCAM-1 in HRMECs. TIMP-3 significantly decreased spontaneous and TNF-Alpha-and VEGF-induced adherence of monocytes to HRMECs. TIMP-3 significantly attenuated VEGF-induced migration, chemotaxis and proliferation of HRMECs. |
| Conclusion | In vitro and in vivo data point to the anti-inflammatory and anti-angiogenic effects of TIMP-3. |
| Conflict of interest | No |
Authors 1
| Last name | ABU EL-ASRAR |
| Initials of first name(s) | A |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 2
| Last name | AHMAD |
| Initials of first name(s) | A |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 3
| Last name | NAWAZ |
| Initials of first name(s) | M |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 4
| Last name | SIDDIQUEI |
| Initials of first name(s) | M |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 5
| Last name | ZUTTER |
| Initials of first name(s) | A |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 6
| Last name | VAN BRABANT |
| Initials of first name(s) | L |
| City | Leuven |
| Country | Belgium |
Authors 7
| Last name | GIKANDI |
| Initials of first name(s) | P |
| City | Riyadh |
| Country | Saudi Arabia |
Authors 8
| Last name | STRUYF |
| Initials of first name(s) | S |
| City | Leuven |
| Country | Belgium |
Authors 9
| Last name | OPDENAKKER |
| Initials of first name(s) | G |
| City | Leuven |
| Country | Belgium |
