Effect of retinal laser photocoagulation on the activity of metalloproteinases and the á2-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathaty

SÁNCHEZ MC; LUNA JD; BARCELONA PF; GRAMAJO AL; JUAREZ PC; RIERA CM; CHIABRANDO GA

EXPERIMENTAL EYE RESEARCH

ELSEVIER

Año: 2007 vol. 85 p. 644 - 650

0014-4835

Panretinal photocoagulation (PRP) reduces the incidence of severe visual loss in proliferative diabetic retinopathy (PDR). The aim of the study was to determine the effect of PRP on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, and also on the á2-Macroglobulin (á2M) proteolytic state in the vitreous of eyes with PDR. Vitreous samples were obtained from patients undergoing vitrectomy for the treatment of retinal diseases: 17 with PDR and 8 with idiopathic macular hole (MH). Qualitative evaluation of the MMP-2 and MMP-9 activation status was performed by gelatin zymography and quantitative assay was carried out for vitreous total protein content and á2M. The proteolytic state of á2M was evaluated by Western blotting. Although all vitreous samples contained proMMP-2, increased proMMP-9 and active MMP-9 were detected in PDR samples without PRP. In addition, after PRP the proMMP-9 activity was significantly decreased, whereas the proMMP-2 activity was not affected. Enhanced total protein and á2M concentrations were observed in all vitreous samples from PDR patients with and without previous PRP compared with samples from patients with MH. However, a differential proteolytic state of á2M, expressed as 180/85-90 kDa ratio, was detected among PDR patients with and without PRP treatment. Whereas a low 180/85–90 kDa ratio of a2M in vitreous of PDR patients without PRP was observed, a high proportion of 180 kDa subunit was principally detected in PDR with PRP. These results demonstrate that PDR occurs with an enhanced activity of MMP-9 and activation of á2M by proteinases, which is reversed after PRP. In addition, we suggest that a2M plays a key role in the control and regulation of the ocular neovascularization involved in the pathogenesis of ischemic retinal diseases such as PDR.