Nanomechanical mapping helps explain differences in outcomes of eye microsurgery: A comparative study of macular pathologies

Many ocular diseases are associated with an alteration of the mechanical and the material properties of the eye. These mechanically-related diseases include macular hole and pucker, two ocular conditions due to the presence of abnormal physical tractions acting on the retina. A complete relief of these tractions can be obtained through a challenging microsurgical procedure, which requires the mechanical peeling of the internal limiting membrane of the retina (ILM). In this paper, we provide the first comparative study of the nanoscale morphological and mechanical properties of the ILM in macular hole and macular pucker. Our nanoscale elastic measurements unveil a different bio-mechanical response of the ILM in the two pathologies, which correlates well to significant differences occurring during microsurgery. The results here presented pave the way to the development of novel dedicated microsurgical protocols based on the material ILM properties in macular hole or pucker. Moreover, they contribute to clarify why, despite a common aetiology, a patient might develop one disease or the other, an issue which is still debated in literature

Macular impairment in fabry disease: A morpho-functional assessment by swept-source OCT angiography and focal electroretinography

PURPOSE. Fabry disease (FD) is a multiorgan X-linked condition characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in a progressive intralysosomal deposit of globotriaosylceramide. The aim of this study was to evaluate the macular ultrastructure of the vascular network using optical coherence tomography angiography (OCTA) and to evaluate macular function using focal electroretinography (fERG) in Fabry patients (FPs). METHODS. A total of 20 FPs (38 eyes, mean age 57 \ub1 2.12 SD, range of 27\u201380 years) and 17 healthy controls (27 eyes, mean age 45 years \ub1 20.50 SD, range of 24\u201365 years) were enrolled in the study. Color fundus photography, swept-source optical coherence tomography (SS-OCT), OCTA and fERG were performed in all subjects. The OCTA foveal avascular zone (FAZ), vasculature structure, superficial and deep retinal plexus densities (images of 4.5 X 4.5 mm) and fERG amplitudes were measured. Group differences were statistically assessed by Student\u2019s t-test and ANOVA. RESULTS. In the FP group, the FAZ areas of the superficial and deep plexuses were enlarged (P = 0.036, t = 2.138; P < 0.001, t = 3.889, respectively), the vessel density was increased in the superficial plexus, and the fERG amplitude was reduced (P < 0.001, t = 10.647) compared with those in healthy controls. No significant correlations were found between the structural and functional data. CONCLUSIONS. OCTA vascular abnormalities and reduced fERG amplitudes indicate subclinical signs of microangiopathy with early retinal dysfunction in FPs. This study highlights the relevance of OCTA imaging analysis in the identification of abnormal macular vasculature as an ocular hallmark of FD

Oxidised LDL (OxLDL) induces production of platelet derived growth factor AA (PDGF AA) from aortic smooth muscle cells

Objectives: Elevated concentrations of oxidised low density lipoproteins (OxLDL) are associated with accelerated atherogenesis. The aim of our study was to determine the effect of OxLDL on the proliferation rate and platelet derived growth factor (PDGF) AA production on aortic smooth muscle cells. High density lipoproteins (HDL), which are known to have a protective effect against atherosclerosis, were used as control. Materials and methods: Bovine aortic smooth muscle cells were grown in presence of increased concentrations of OxLDL and HDL and in presence of control medium culture (DMEM). Proliferation rate was assessed by 3H-thymidine uptake. PDGF AA production was determined by ELISA and Western Blot Analysis. Results: OxLDL increased the proliferation rate of aortic smooth muscle cells as compared to DMEM and HDL (p < 0.001). The mitogenic activity of OxLDL on smooth muscle cells was reduced adding anti-PDGF AA antibodies (p < 0.001). PDGF AA production by aortic smooth muscle cells was increased after exposure to OxLDL as compared to DMEM (p < 0.001). HDL significantly reduced the production of PDGF AA by aortic smooth muscle cells (p < 0.001). Conclusions: Part of the atherogenic effect of OxLDL is mediated through the autocrine production of PDGF AA from aortic smooth muscle cells

Shear stress induces transforming growth factor-beta 1 release by arterial endothelial cells

Myointimal hyperplasia is a common complication after vascular reconstruction. Increasing shear stress has been shown to reduce formation of myointimal hyperplasia. The aims of our study were (1) to analyze the correlation between shear stress and release of transforming growth factor (TGF)-beta 1 by endothelial cells and (2) to determine the effect of TGF-beta 1 on smooth muscle cell proliferation

Thioredoxin specifically cross-desensitizes monocytes to MCP-1

8nonenonePAGLIEI S; GHEZZI P; BIZZARRI C; SABBATINI V; FRASCAROLI G; S. SOZZANI; CASELLI G; BERTINI RPagliei, S; Ghezzi, P; Bizzarri, C; Sabbatini, V; Frascaroli, G; Sozzani, Silvano; Caselli, G; Bertini, R

Oxidised LDL (OxLDL) induces production of platelet derived growth factor AA (PDGF AA) from aortic smooth muscle cells.

OBJECTIVES: Elevated concentrations of oxidised low density lipoproteins (OxLDL) are associated with accelerated atherogenesis. The aim of our study was to determine the effect of OxLDL on the proliferation rate and platelet derived growth factor (PDGF) AA production on aortic smooth muscle cells. High density lipoproteins (HDL), which are known to have a protective effect against atherosclerosis, were used as control. MATERIALS AND METHODS: Bovine aortic smooth muscle cells were grown in presence of increased concentrations of OxLDL and HDL and in presence of control medium culture (DMEM). Proliferation rate was assessed by 3H-thymidine uptake. PDGF AA production was determined by ELISA and Western Blot Analysis. RESULTS: OxLDL increased the proliferation rate of aortic smooth muscle cells as compared to DMEM and HDL (p < 0.001). The mitogenic activity of OxLDL on smooth muscle cells was reduced adding anti-PDGF AA antibodies (p < 0.001). PDGF AA production by aortic smooth muscle cells was increased after exposure to OxLDL as compared to DMEM (p < 0.001). HDL significantly reduced the production of PDGF AA by aortic smooth muscle cells (p < 0.001). CONCLUSIONS: Part of the atherogenic effect of OxLDL is mediated through the autocrine production of PDGF AA from aortic smooth muscle cells

Thrombin induces production of growth factors from aortic smooth muscle cells.

Background. Myointimal hyperplasia is a common complication of arterial recontructive surgery. The serine protease thrombin has a major role in vessel wall healing and eventual myointimal hyperplasia formation. The aim of this study was to determine the effect of thrombin on the production of PDGF AA and bFGF by arterial smooth muscle cells. Materials and methods. Bovine smooth muscle cells were stimulated with thrombin in a serum-free culture. The release of PDGF AA and bFGF was assessed by ELISA. The effect of thrombin on the proliferation of confluent monolayers of bovine smooth muscle cells was determined by tritiated thymidine uptake. Results. Smooth muscle cells stimulated with thrombin released more PDGF AA (P < 0.001) and bFGF (P < 0.001) than the control. Addition of anti-PDGF AA and anti-bFGF antibodies to the medium of smooth muscle cell cultures neutralized the mitogenic effect of thrombin (P < 0.001). Conclusions. The findings of our study suggest that thrombin may lead to myointimal hyperplasia formation through induction of PDGF and bFGF production by smooth muscle cells