Biomedicines. 2022 Jun 30;10(7):1557. doi: 10.3390/biomedicines10071557. PMID: 35884862
Abstract: Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role
in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have
demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10-/- mice developed smaller
laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.
in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have
demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10-/- mice developed smaller
laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.
Funding: The present work was partially funded by Thea Laboratoires (01/2019), Fundación Jesús Gangoiti Barrera (2020–2021) and a collaborative project with Multiópticas (CUN 2019). Moreover, the work was partially supported by Red Temática de Investigación Cooperativa en Salud: ‘Prevention, Early Detection and Treatment of the Prevalent Degenerative and Chronic Ocular Pathology’ (RD16/0008/0011), Redes de Investigación Cooperativa Orientadas al Resultado en Salud (RICORS) de Terapias avanzadas (RD21/0017/0027), Enfermedades Inflamatorias (RD21/0002/0010) y Enfermedades vasculares cerebrales (RD21/0006/0008), Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, 28029 Madrid, Spain.