tacrolimus and Vitreoretinopathy--Proliferative

The transforming growth factor β (TGFβ) family plays an important role in the pathogenesis of many diseases, including fibrotic pathologies of the eyes. The difficulties of surgical procedures contribute to the search for new treatment strategies for proliferative vitreoretinopathy. Therefore, the aim of this study was to investigate the expression profile of TGFβ isoforms, their receptors, and TGFβ-related genes in human retinal pigment epithelial cells (RPE) after tacrolimus (FK-506) treatment in the presence or absence of lipopolysaccharide (LPS)-induced inflammation.. The expression profile was analyzed using oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) techniques.. Analysis using oligonucleotide microarrays revealed 20 statistically significant differentially expressed TGFβ-related genes after LPS treatment in relation to control cells, and after tacrolimus and LPS treatment in relation to LPS-treated cells. Moreover, our results showed that mRNA levels for TGFβ2 and TGFβR3 after tacrolimus treatment, and for TGFβR3 after tacrolimus and LPS treatment in RPE cells were decreased. In turn, in the presence of LPS-induced inflammation, TGFβ2 mRNA level was increased.. These results can be important in regard to the treatment of proliferative vitreoretinopathy, pathogenesis of which is associated with processes regulated by TGFβ, such as inflammation, proliferation, epithelial-mesenchymal transition (EMT), and fibrosis.

Topics: Cells, Cultured; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Inflammation; Retinal Pigment Epithelium; RNA, Messenger; Signal Transduction; Tacrolimus; Transforming Growth Factor beta; Vitreoretinopathy, Proliferative

To investigate the effect of intravitreal tacrolimus on an animal model of proliferative vitreoretinopathy (PVR) and on growth factors implicated in its pathogenesis.. Twenty-one guinea pigs were randomly assigned to one of three groups of seven animals each: no-PVR/saline group (no PVR/intravitreal saline-injected group), PVR/saline group (dispase-induced PVR group, treated with control injections of intravitreal saline), and PVR/tacrolimus group (treatment group, dispase-induced PVR group treated with intravitreal tacrolimus injections). At the end of the experiment, eyes were enucleated and the identification of the stages of PVR was carried out. While a halves of the enucleated globes were evaluated histopathologically for PVR formation, the retinas of the other halves of globes were used for the preparation of retinal homogenates. The transforming growth factor-β, platelet-derived growth factor, and fibroblast growth factor levels in homogenized retina tissues were measured by the enzyme-linked immunosorbent assay method.. When assessing the average PVR stages in terms of severe PVR rates, the PVR/tacrolimus group had significantly improved when compared with the PVR/saline group. The PVR/tacrolimus group demonstrated significantly decreased levels of transforming growth factor-β, platelet-derived growth factor, and fibroblast growth factor when compared with the PVR/saline group and also demonstrated significant improvement in epiretinal membrane formation and retinal fold in the presence of histopathologic levels. The difference in degradation of photoreceptor cells between the PVR/tacrolimus and the PVR/saline groups was not statistically significant.. This study suggests that intravitreal tacrolimus application may suppress PVR development and that tacrolimus may merit investigation for the prophylaxis of PVR.

Topics: Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibroblast Growth Factor 2; Guinea Pigs; Immunosuppressive Agents; Intercellular Signaling Peptides and Proteins; Intravitreal Injections; Platelet-Derived Growth Factor; Tacrolimus; Transforming Growth Factor beta; Vitreoretinopathy, Proliferative