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The Y1 receptor of neuropeptide Y (NPY) has been demonstrated in glial cells of astrocytic lineage in vitro. We have studied the immunohistochemical expression of Y1 receptors in the glia of the diseased human retina, in tissue samples obtained after surgery for proliferative vitreoretinopathy. In this condition, glia and other cell types migrate and form epi- or subretinal membranes. Both diseased retinas (n = 8) and PVR membranes (n = 43) contained numerous Y1-immunoreactive cells. In the diseased retina, the Y1 antiserum labeled cells with the morphological radial pattern characteristic of Müller cells, whereas in the membranes, label appeared in a large population of elongate cells, measuring up to 250 microm. In both retina and membranes, double labeling demonstrated that the vast majority of Y1-immunoreactive cells were also labeled by a glial fibrillary acidic protein (GFAP) antibody, indicating their glial origin. Retinal regions devoid of GFAP immunoreactivity also lacked the Y1 label. None of these markers was detected in Müller cells of normal retina. Y1 immunoreactivity did not co-localize with smooth muscle actin immunoreactivity, a marker of myofibroblasts. Expression of Y1 receptors would characterize reactive and proliferating glial cells of the diseased retina and could perhaps be involved in the proliferation of injured glial cells causing regrowth of PVR membranes and the consequent secondary retinal detachments.

Autologous limbal epithelial cell transplantation improved the corneal surface in eyes with LSCD. Photocoagulation of neovessel ingrowth was effective over the 1-year follow-up. Results may facilitate the application of this technique in patients.

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Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.Electronic supplementary materialThe online version of this article (doi:10.1186/0717-6287-47-58) contains supplementary material, which is available to authorized users.

Diabetes produces several changes in the body triggered by high glycemia. Some of these changes include altered metabolism, structural changes in blood vessels and chronic inflammation. The eye and particularly the retinal ganglion cells (RGCs) are not spared, and the changes eventually lead to cell loss and visual function impairment. Understanding the mechanisms resulting in RGC damage and loss from diabetic retinopathy is essential to find an effective treatment. This review focuses mainly on the signaling pathways and molecules involved in RGC loss and the potential therapeutic approaches for the prevention of this cell death. Throughout the manuscript it became evident that multiple factors of different kind are responsible for RGC damage. This shows that new therapeutic agents targeting several factors at the same time are needed. Alpha-1 antitrypsin as an anti-inflammatory agent may become a suitable option for the treatment of RGC loss because of its beneficial interaction with several signaling pathways involved in RGC injury and inflammation. In conclusion, alpha-1 antitrypsin may become a potential therapeutic agent for the treatment of RGC loss and processes behind diabetic retinopathy.

BackgroundThe contemporary peak of diabetes seems to be related to obesity, sedentary lifestyle and diet. Diabetic retinopathy is the most leading cause of blindness in adulthood in industrialized countries. Our purpose was to evaluate the effect of a high-fat-diet (HFD) on the retina of diabetic rats.MethodsTwo groups of Wistar rats were injected with streptozotocin (STZ) two days after birth using 45 and 90 mg/kg, respectively. At 8 weeks the group on lower doses started to be fed on a HFD. Animals were sacrificed at 37 weeks of diabetes. A control group was made up of non-diabetic rats. Retinal flat mounts were examined using the trypsin digestion technique. Pericytes counts were compared between diabetic and control rats. Cross retinal sections were analyzed by histological techniques and immunohistochemistry and immunofluorescent technique. Primary antibodies against inflammatory and proangiogenic mediators such as RAGE, GFAP, 5-LO, VEGF and TNF-α were used for immunohistochemistry and Western Blot (WB) analyses.ResultsIn the two diabetic groups we observed GFAP-positive cells with a morphology and spatial organization similar to those seen in Müller cells. Both diabetic groups had a significantly lower number of pericytes than non-diabetic animals.Increased retinal immunoreactivity of GFAP, RAGE, TNF-α, VEGF and 5-LO was seen in diabetic animals fed on HFD compared to the other groups of animals. WB analysis revealed a higher expression of 5-LO, VEGF, TNF-α and RAGE in the retina of diabetic rats on HFD than in controls and diabetics fed on a normal diet. The percentage of RAGE-stained ganglion cells and ganglion cells was found to be significantly lower in animals on a HFD than in the other animals.ConclusionsDiabetic animals fed on a HFD showed an increased upregulation of inflammatory and proangiogenic markers. This animal model may be useful to study mechanisms of diabetic retinopathy and therapeutic targets.