Sirpa Loukovaara

Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFβ1 in diabetic eyes undergoing vitrectomy.

Purpose:  Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia‐induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 (MMP‐2 and MMP‐9), angiopoietin‐1 and angiopoietin‐2 (Ang‐1 and Ang‐2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor‐β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker.

Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients.

Initial triggers for diabetic retinopathy (DR) are hyperglycemia-induced oxidative stress and advanced glycation end-products. The most pathological structural changes occur in retinal microvasculature, but the overall development of DR is multifactorial, with a complex interplay of microvascular, neurodegenerative, genetic/epigenetic, immunological, and secondary inflammation-related factors. Although several individual factors and pathways have been associated with retinopathy, a systems level understanding of the disease is lacking. To address this, we performed mass spectrometry based label-free quantitative proteomics analysis of 138 vitreous humor samples from patients with nonproliferative DR or the more severe proliferative form of the disease. Additionally, we analyzed samples from anti-VEGF (vascular endothelial growth factor) (bevacizumab)-treated patients from both groups. In our study, we identified 2482 and quantified the abundancy of 1351 vitreous proteins. Of these, the abundancy of 230 proteins was significantly higher in proliferative retinopathy compared with nonproliferative retinopathy. This specific subset of proteins was linked to inflammation, complement, and coagulation cascade proteins, protease inhibitors, apolipoproteins, immunoglobulins, and cellular adhesion molecules, reflecting the multifactorial nature of the disease. The identification of the key molecules of the disease is critical for the development of new therapeutic molecules and for the new use of existing drugs.

Elevated protein carbonyl and HIF-1α levels in eyes with proliferative diabetic retinopathy.

Purpose:  To evaluate the role of protein carbonyls and hypoxia inducible factor‐1α (HIF‐1α) in diabetic eyes with proliferative diabetic retinopathy (PDR).

NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy

Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide‐binding domain and Leucine‐rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro‐inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight‐threatening forms of diabetic retinopathy (DR).

Progression of Retinopathy in Type 1 Diabetic Women During Pregnancy

Progression of diabetic retinopathy (DR) occurs at least temporarily during pregnancy and postpartum. The pathogenetic mechanisms of DR progression during pregnancy are not fully understood. Several factors related to metabolic changes (hyperglycaemia), diabetes itself (duration of diabetes before conception, baseline status of DR), pregnancy physiology (hypervolaemia and hypercoagulation, impaired retinal autoregulation) and pregnancy complications (pre-eclampsia) seem to play important roles in the progression of DR during pregnancy. On the other hand, systemic angiopoietic and vasoactive factors seem to have minor role in the deterioration of DR during that time period. Good glycaemic control, normotension, lack of nephropathy as well as lack of pre-proliferative/proliferative changes of DR are good prognostic factors as regards the progression of DR during pregnancy. However, pregnancy seems to have no long-term detrimental effects as regards the progression of DR unless it has proceeded to pre-proliferative and proliferative phases.

Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) is characterized by ischaemia‐ and inflammation‐induced neovascularization, but the pathological vascular differentiation in PDR remains poorly characterized. Here, endothelial progenitor and growth properties, as well as potential lymphatic differentiation, were investigated in the neovascular membrane specimens from vitrectomized patients with PDR.

Low intravitreal angiopoietin‐2 and VEGF levels in vitrectomized diabetic patients with simvastatin treatment

To investigate the intravitreal levels of potent vasoactive, angiogenic and extracellular matrix remodelling factors in the diabetic patients with simvastatin treatment.

Increased intravitreal adenosine 5′‐triphosphate, adenosine 5′‐diphosphate and adenosine 5′‐monophosphate levels in patients with proliferative diabetic retinopathy

Extracellular purines play important role in ocular physiology, diabetes, vascular remodelling and adaptation to inflammation. This study was aimed to evaluate intravitreal purine levels in patients with diabetic retinopathy (DR) and other non‐vascular vitreoretinal eye diseases.

Improved outcome after primary vitrectomy in diabetic patients treated with statins.

Purpose To evaluate the effect of preoperative statin treatment on the outcome of primary vitrectomy in type 1 and 2 diabetic patients. Methods In this open, observational institutional study, a total of 192 eyes of 171 type 1 and 2 adult diabetic patients admitted for primary vitrectomy for management of sight-threatening forms of diabetic retinopathy were divided according to the use of lipid-lowering therapy: those with statin treatment (79 eyes of 73 patients) and those taking no statin medication (113 eyes of 98 patients). One-month best-corrected visual acuity (BCVA) gain and cumulative 12-month revitrectomy frequency were analyzed. Results In multivariate linear regression, diabetic patients with statin treatment had a better 1-month BCVA improvement than did those without statin treatment (absolute difference 0.26, 95% confidence interval [CI] 0.02-0.50, p = 0.028). Subgroup analysis revealed that diabetic patients on statin had better postoperative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p = 0.042 and p = 0.049) and anti-vascular endothelial growth factor therapy (p = 0.011). Moreover, diabetic patients with preoperative macular edema (p = 0.009), vitreous hemorrhage (p<0.001), proliferative retinopathy (p<0.001), or tractional retinal detachment (p = 0.010) had better BCVA recovery if receiving statin. In Cox proportional hazards regression model, revitrectomies in our 12-month follow-up were less frequent in diabetic patients on statin treatment (hazard ratio 0.28, 95% CI 0.08-0.93, p = 0.037). Conclusions These data provide novel insight into the potential clinical benefit for patients with sight-threatening diabetic retinopathy undergoing vitrectomy treated with statin.

Poor glycemic control associates with high intravitreal angiopoietin‐2 levels in patients with diabetic retinopathy

and wanted the mass removed. In view of the presented symptoms and risk of corneal endothelium injury due to the continuously touch with the cyst, surgical removal was suggested. Prior to surgery, 2% pilocarpine drops (tid) was administered to keep the pupil constricted. Surgery was performed under topical anesthesia. A limbal paracentesis of 1.2 mm was performed at 2 o’clock position, and a small volume of viscoelastic was injected into the anterior chamber. Then, amajor limbal incision of 2.8 mm was made at 12 o’clock position. The iris cyst moved through themajor incision with aqueous right away, when viscoelastic was injected slowly through the major incision. The sample of cyst was collected immediately and fixed in 10% formaldehyde solution. The incisions were then sealed by hydration. The surgery was completed in 10 min. Therewasminimal inflammation in the anterior chamber for a few days and had no signs of any lenticular changes. The best-corrected visual acuity was 20/20 in day 1 after the operation. The pathohistological examinationof the cyst demonstrated a folded epithelium lining composed of mature pigment epithelium (Fig. 1D). This was consistent with the clinical diagnosis of a cyst of the iris pigment epithelium. No recurrence of cyst and any other ocular complications were observed during the succeeding 6-month followup. Our case suggested that surgical removal of free-floating iris cyst in anterior chamber could be an effective choice of treatment.