The role of oxidative stress in glaucoma

Glaucoma has long been considered exclusively a disease of the eye. Today it is known that glaucoma is an occular manifestation of systemic diseases. The pathomechanisms of glaucoma seem to be similar to those observed in other neurodegenerative disorders such as Alzheimer’s disease where nerve cell death, oxidative damage and inflammatory response are observed. The one known and proved glaucoma risk factor – elevated intraocular pressure (IOP), is neither necessary nor sufficient for the development and progression of glaucoma. What is more, IOP normalization does not always prevent disease progression. The data on oxidative stress in glaucomatous disturbances seem not only to conflict other observations but rather complement the mechanical, vascular, genetic and immunologic theories of glaucoma pathogenesis. The aim of the work is a summary of the latest research on the role of oxidative stress in glaucoma.Do niedawna jaskra była uważana za schorzenie wyłącznie okulistyczne. Dzisiaj wiadomo, że jest ona oczną manifestacją ogólnoustrojowych zaburzeń. Patomechanizmy występujące w jaskrze wydają się podobne do obserwowanych w pozostałych chorobach neurodegeneracyjnych, takich jak np. choroba Alzheimera, gdzie obserwuje się śmierć komórek nerwowych, uszkodzenia związane z szokiem tlenowym, azotowym i odpowiedzią zapalną. Jedyny znany i potwierdzony czynnik ryzyka jaskry – podwyższone ciśnienie wewnątrzgałkowe (CWG) nie jest ani wystarczający, ani konieczny do rozwoju i progresji jaskry. Normalizacja CWG często nie zapobiega postępowi choroby. Obserwacje związku stresu oksydacyjnego z jaskra zdają się nie tylko nie zaprzeczać innym teoriom rozwoju jaskry (mechanicznym, naczyniopochodnym, genetycznym i immunologicznym), ale je uzupełniać. Celem pracy jest zestawienie najnowszych wyników badań nad rolą stresu oksydacyjnego w patogenezie jaskry

The influence of elastin degradation products, glucose and atorvastatin on metalloproteinase-1, -2, -9 and tissue inhibitor of metalloproteinases-1, -2, -3 expression in human retinal pigment epithelial cells

Purpose: Hyperglycemia and increased concentrations of elastin degradation products (EDPs) are common findings in patients with diabetes, atherosclerosis and hypertension. The aim of this study was to assess the influence of high glucose, EDPs and atorvastatin on MMP-1, MMP-2, MMP-9 and TIMP1-3 gene expression in human retinal pigment epithelial cells (HRPE) in vitro. Method: HRPE were cultured for 24 hours with the substances being tested (glucose, EDPs), alone or in combination. Additionally, the cells were treated with atorvastatin in two different concentrations (1 or 10 μM). After incubation, total cellular RNA was extracted and used for gene expression evaluation. Gene expression was measured using the real-time RT-PCR technique. Results: Glucose, EDPs and atorvastatin had no impact on TIMP-1 and TIMP-3 expression. HRPE cells treated with glucose or EDPs with the addition of atorvastatin had a statistically significant decrease of TIMP-2 expression; glucose alone decreased MMP-1 expression. Atorvastatin decreased expression of all assessed genes, except TIMP-1 and TIMP-3 in a dose-dependent manner. Conclusions: Our results confirm the importance of MMPs and TIMPs in retinal vascular biology. Atorvastatin-induced MMPs gene expression can deeply affect extracellular matrix turnover, which may play an important role in the progression of ocular diseases

Gene Expression of IGF1, IGF1R, and IGFBP3 in Epiretinal Membranes of Patients with Proliferative Diabetic Retinopathy: Preliminary Study

The molecular mechanism formation of secondary epiretinal membranes (ERMs) after proliferative diabetic retinopathy (PDR) or primary idiopathic ERMs is still poorly understood. Therefore, the present study focused on the assessment of IGF1, IGF1R, and IGFBP3 mRNA levels in ERMs and PBMCs from patients with PDR. The examined group comprised 6 patients with secondary ERMs after PDR and the control group consisted of 11 patients with idiopathic ERMs. Quantification of IGF1, IGF1R, and IGFBP3 mRNAs was performed by real-time QRT-PCR technique. In ERMs, IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects. In PBMCs, there were no statistically significant differences of IGF1, IGF1R, and IGFBP3 expression between diabetic and nondiabetic patients. In conclusion, our study indicated IGF1 and IGF1R differential expression in ERMs, but not in PBMCs, of diabetic and nondiabetic patients, suggesting that these factors can be involved in the pathogenesis or progression of proliferative vitreoretinal disorders. This trial is registered with NCT00841334