Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha2-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy?.

SANCHEZ MC; LUNA JD; BARCELONA PF; GRAMAJO L; JUAREZ CP; RIERA CM; CHIABRANDO GA

EXPERIMENTAL EYE RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

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 studywas to determine the effect of PRP on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, and also on the a2-Macroglobulin (a2M)proteolytic state in the vitreous of eyes with PDR. Vitreous samples were obtained from patients undergoing vitrectomy for the treatment ofretinal diseases: 17 with PDR and eight with idiopathic macular hole (MH). Qualitative evaluation of the MMP-2 and MMP-9 activation statuswas performed by gelatin zymography and quantitative assay was carried out for vitreous total protein content and a2M. The proteolytic state ofa2M was evaluated by Western blotting. Although all vitreous samples contained proMMP-2, increased proMMP-9 and active MMP-9 weredetected 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 a2M 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 a2M, expressed as 180/85e90 kDaratio, was detected among PDR patients with and without PRP treatment. Whereas a low 180/85e90 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 demonstratethat PDR occurs with an enhanced activity of MMP-9 and activation of a2M by proteinases, which is reversed after PRP. In addition, we suggestthat a2M plays a key role in the control and regulation of the ocular neovascularization involved in the pathogenesis of ischemic retinal diseasessuch as PDR