ABSTRACT
Alpha-2-macroglobulin (α2-MG) is a multifunctional protein involved in neurodegeneration, inflammation and neovascularization, which are key processes in the pathogenesis of age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). AMD and PDR are two of the main causes of vision loss and blindness, are difficult to treat, and are generally diagnosed at the stage of irreversible changes. PURPOSE: This study estimates the activity of α2-MG in the blood serum and tears of patients with AMD and PDR in order to reveal the relation of its levels with the intensity of the pathological process in the retina. MATERIAL AND METHODS: The study included 17 patients (34 eyes) with AMD, 15 patients (30 eyes) with PDR, and 15 healthy adults (30 eyes) of the similar age. The activity of α2-MG in serum and tears was measured enzymatically using the specific substrate N-benzoyl-DL-arginine-p-nitroanilide (BAPNA). RESULTS: The activity of α2-MG in tears of patients with AMD was on the average 3.5 times higher than in healthy controls, and in patients with PDR - 1.5 times higher. Patients with AMD at the submacular fibrosis stage showed decreased α2-MG activity in tears. The activity of α2-MG in serum of patients with AMD and PDR was on the average 25% higher than in healthy persons. No correlation was revealed between serum and tear levels of α2-MG activity. CONCLUSION: This study revealed for the first time that in AMD and PDR the activity of α2-MG in tears is increased, and that in AMD the increase is higher than in PDR. An increase of α2-MG activity in serum confirms the presence of systemic inflammation. Absence of correlation between the serum and tear activity of α2-MG confirms its local origin. The high level of α2-MG activity in tears reflects the presence of an active destructive process in the retina, justifying its further investigation as a predictor of AMD and PDR course, as well as an indicator of therapy effectiveness.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Degeneration , Humans , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/etiology , Diabetic Retinopathy/metabolism , Inflammation , Macroglobulins , Macular Degeneration/diagnosis , Macular Degeneration/etiology , Retina , Serum/metabolismABSTRACT
Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.