Abstract Background: To investigate whether macular structure could be affected by axial elongation and to determine the association between macular intraretinal thickness and the microstructure of β-zone parapapillary atrophy (PPA) in myopic eyes. Methods: The study recruited 113 healthy myopic subjects (113 eyes). Images of the macula, subfoveal choroid, and optic nerve head were acquired using spectral-domain optical coherence tomography (SD-OCT). An automatic segmentation algorithm was used to segment the macular images into 7 intraretinal layers. PPA widths with and without Bruch’s membrane (PPA+BM and PPA-BM, respectively) were evaluated. Linear regression analysis was performed to evaluate the association between macular intraretinal thickness and axial length and the microstructure of PPA. Results: An increase in axial length was associated with a decrease in whole macular thickness of the peripheral region and an increase in whole macular thickness of the central region. Thickness alterations of the macular intraretinal layers were most apparent in the peripheral region. A significant correlation was found between PPA-BM width and macular intraretinal layer thickness, whereas no significant correlation was found between PPA+BM width and macular intraretinal layer thickness. Moreover, both PPA+BM and PPA-BM widths significantly correlated with subfoveal choroidal thickness. Conclusions: Macular intraretinal layer thickness may be affected by PPA-BM width. These findings indicate that the microstructure of PPA should be considered when evaluating the macula in patient with myopia and glaucoma.
Abstract We investigated the relationship between microstructure of β-parapapillary atrophy (β-PPA) and morphologic features of optic nerve head (ONH) and posterior pole in highly myopic eyes. Eighty-nine highly myopic eyes were included in this study. Bruch’s membrane opening (BMO) area, lamina cribrosa (LC) thickness, anterior laminar depth, peripapillary and subfoveal choroidal thickness (CT), macular Bruch’s membrane (BM) length, and width of β-PPA with and without Bruch’s membrane (PPA +BM and PPA −BM ) were evaluated. The mean age and axial length of the included subjects were 26.88 ± 2.44 years and 27.03 ± 0.88 mm, respectively. The width of PPA −BM was larger with increasing BMO area ( P = 0.001), whereas the BMO area was not associated with the width of PPA +BM . The large PPA +BM was significantly related to a thinner LC ( P = 0.003), deeper anterior lamina surface ( P < 0.001), longer macular BM length ( P = 0.008), and thinner temporal peripapillary CT ( P = 0.034). We found that the morphologic features of the ONH and posterior pole in highly myopic eyes were different based on the microstructure of β-PPA. Whether these features are linked to the development of glaucoma in myopic eyes should be investigated in future studies.
Abstract This study explored the association between foveal avascular zone (FAZ) parameters and high myopia using optical coherence tomography angiography. We divided 106 eyes of 106 patients into quartiles based on the axial length. The upper quartile was then defined as the high myopia group (n = 27), while the lower quartile was the non-high myopia group (n = 26). The areas and minor axis lengths of superficial and deep FAZ, the perimeters and major axis lengths of deep FAZ were significantly larger in eyes with high myopia than in eyes with non-high myopia ( P < 0.05). Inversely, the subfoveal choroidal thickness was significantly thinner in eyes with high myopia than in those with non-high myopia. Linear regression analyses showed that no significant correlation was observed between FAZ areas and acircularity and circularity indexes of FAZ in non-high myopia group. Conversely, FAZ areas strongly correlated with acircularity and circularity indexes of FAZ in high myopia group. We found that an increase in the FAZ area in highly myopic eyes was accompanied by a significant variation in FAZ acircularity and circularity indexes. Further research should address whether these findings are associated with future disease development in highly myopic eyes.
Phosphorylation is one of the most common post-translational modifications. The phosphorylation of the kinase-inducible domain (KID), which is an intrinsically disordered protein (IDP), promotes the folding of KID and binding with the KID-interacting domain (KIX). However, the regulation mechanism of the phosphorylation on KID is still elusive. In this study, the structural ensembles and binding process of pKID and KIX are studied by all-atom enhanced sampling technologies. The results show that more hydrophobic interactions are formed in pKID, which promote the formation of the special hydrophobic residue cluster (HRC). The pre-formed HRC promotes binding to the correct sites of KIX and further lead the folding of pKID. Consequently, a flexible conformational selection model is proposed to describe the binding and folding process of intrinsically disordered proteins. The binding mechanism revealed in this work provides new insights into the dynamic interactions and phosphorylation regulation of proteins.
The free energy landscapes of 4E-BP2 and its variants were obtained by replica-exchanged molecular dynamics, which elucidate the regulation mechanism of phosphorylation and mutations on the intrinsically disordered protein.
Abstract Background To investigate whether macular structure could be affected by axial elongation and to determine the association between macular intraretinal thickness and the microstructure of β-zone parapapillary atrophy (PPA) in myopic eyes. Methods The study recruited 113 healthy myopic subjects (113 eyes). Images of the macula, subfoveal choroid, and optic nerve head were acquired using spectral-domain optical coherence tomography (SD-OCT). An automatic segmentation algorithm was used to segment the macular images into 7 intraretinal layers. PPA widths with and without Bruch’s membrane (PPA +BM and PPA -BM , respectively) were evaluated. Linear regression analysis was performed to evaluate the association between macular intraretinal thickness and axial length and the microstructure of PPA. Results An increase in axial length was associated with a decrease in whole macular thickness of the peripheral region and an increase in whole macular thickness of the central region. Thickness alterations of the macular intraretinal layers were most apparent in the peripheral region. A significant correlation was found between PPA -BM width and macular intraretinal layer thickness, whereas no significant correlation was found between PPA +BM width and macular intraretinal layer thickness. Moreover, both PPA +BM and PPA -BM widths significantly correlated with subfoveal choroidal thickness. Conclusions Macular intraretinal layer thickness may be affected by PPA -BM width. These findings indicate that the microstructure of PPA should be considered when evaluating the macula in patient with myopia and glaucoma.
As a member of the fatty acids transporter family, the heart fatty acid binding proteins (HFABPs) are responsible for many important biological activities. The binding mechanism of fatty acid with FABP is critical to the understanding of FABP functions. The uncovering of binding-relevant intermediate states and interactions would greatly increase our knowledge of the binding process. In this work, all-atom molecular dynamics (MD) simulations were performed to characterize the structural properties of nativelike intermediate states. Based on multiple 6 μs MD simulations and Markov state model (MSM) analysis, several “open” intermediate states were observed. The transition rates between these states and the native closed state are in good agreement with the experimental measurements, which indicates that these intermediate states are binding relevant. As a common property in the open states, the partially unfolded α2 helix generates a larger portal and provides the driving force to facilitate ligand binding. On the other side, there are two kinds of open states for the ligand-binding HFABP: one has the partially unfolded α2 helix, and the other has the looser β-barrel with disjointing βD-βE strands. Our results provide atomic-level descriptions of the binding-relevant intermediate states and could improve our understanding of the binding mechanism.
Purpose The current study was undertaken to investigate whether Brazilian green propolis (BGP) can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and examined the possible mechanisms underlying this neuroprotection.Materials and Methods C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to establish retinal ischemia-reperfusion injury. Mice then received saline or BGP (200 mg/kg) intraperitoneally once daily until sacrifice. The expression of hypoxia-inducing factor (HIF)-1α and glial fibrillary acidic protein (GFAP) and the level of histone acetylation were assessed at 1, 3, and 7 days after injury. The expression of Bax, Bcl-2, p53, NF-κB, Nrf2, and HO-1 were also analyzed at 3 days after injury. The neuroprotective effect of BGP treatment on RGC survival was evaluated using Brn3a immunohistochemical staining.Results The expression of HIF-1α and GFAP was increased and the level of histone acetylation decreased in saline-treated ischemic retinas within 7 days. BGP treatment effectively attenuated the elevated expression of HIF-1α, GFAP, Bax, NF-κB and p53. The expression of Bcl-2, Nrf2, HO-1 and the level of histone acetylation increased by BGP treatment, resulting in a significant difference between BGP-treated and saline-treated retinas. Immunohistochemical staining for Brn3a also revealed that BGP treatment protected against RGC loss in ischemic retina.Conclusions Our results suggest that BGP has a neuroprotective effect on RGCs through the upregulation of histone acetylation, downregulation of apoptotic stimuli, and suppression of NF-κB mediated inflammatory pathway in ischemic retina. These findings suggest that BGP is a potential neuroprotective agent against RGC loss under oxidative stress.
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