Morphologic and Functional Assessment of Photoreceptors in Laser Induced Retinopathy Using Adaptive Optics-SLO and Microperimetry.

PURPOSE: To assess the cone photoreceptors morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics Scanning Laser Ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN: Cohort study. METHODS: This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion and regularity in AO-SLO were assessed and correlated with visual function. RESULTS: In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478µm², ranging from 6,705 to 673,348µm². Compared to the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all four quadrants at 3° eccentricity (all P values <0.05). Lesion morphology in AO-SLO correlated with EZ defects observed in OCT, showing a positive correlation in size (r = 0.84, P<0.001) but not with retinal sensitivities (P = 0.09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = 0.13). CONCLUSIONS AND RELEVANCE: The study provides crucial insights into the morphological and functional impacts of LIR on cone photoreceptors, revealing significant morphological changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration.

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations. Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes. Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Outcomes of revision surgery for idiopathic macular hole after failed primary vitrectomy.

Persistent idiopathic macular hole (PIMH), the occurrence of idiopathic macular holes that have failed to close after standard pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, has become a global health threat to the aging population. Because postoperative anatomic closure or restoration of visual acuity is more difficult to achieve in PIMH, surgical approaches that would yield the best outcomes remain to be elucidated. On paper, extended ILM peeling combined with silicone oil (SiO) tamponade is believed to be a feasible option for excellent macular hole closure. However, no studies on this combined treatment for PIMH is compared with simple air tamponade have been conducted. Thus, in this retrospective case series, we used spectral-domain optical coherence tomography (SD-OCT) and other technologies to investigate real-world evidence for the anatomical and functional outcomes of revisional PPV with either SiO or air tamponade for failed primary idiopathic macular hole surgery. We included the records of 76 patients with PIMH who had SD-OCT examinations and best-corrected visual acuity (BCVA). Regression analysis was performed to find factors affecting PIMH fracture closure. Seventy-six participants were allocated to a SiO group (n = 21, with an extended ILM peeling and SiO tamponade) or an air group (n = 55, with extended ILM peeling and air tamponade). Anatomical success was achieved in 18 (85.7%) and 40 (72.7%) eyes in the SiO and air groups, respectively (p = 0.37). BCVA was significantly improved in both subgroups of closed PIMH (SiO group: p = 0.041; air group: p < 0.001). Minimum linear diameter (MLD) was closely related to the closure rate (OR, 1.0; 95% CI (0.985-0.999); p = 0.03). MLD = 650 µm seemed like a cut-off point for closure rate (MLD ≤ 650 µm vs. MLD > 650 µm; 88.4% vs. 52%, p = 0.002). In conclusion, we demonstrated that extended ILM peeling combined with SiO or air tamponade is effective in PIMH treatment. Moreover, though not statistically significant herein, the anatomic closure rate was better for silicone-operated eyes than for air-operated eyes. MLD is the best predictor of PIMH closure; MLD ≤ 650 µm could achieve a significantly higher closure rate.

MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway.

Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.

Slit2 suppresses endotoxin-induced uveitis by inhibiting the PI3K/Akt/IKK/NF-κB pathway.

Uveitis is a devastating intraocular inflammatory disease. The secreted leucine-rich repeat protein slit homologue 2 (Slit2) has been found to be an essential regulator of inflammation. This study aimed to analyse the anti-inflammatory effects and the underlying mechanisms of Slit2 in an endotoxin-induced uveitis (EIU) rat model. In this study, rats with EIU pretreated recombinant human Slit2 (rhSlit2) or a control vehicle by intravitreal injection. The clinical scores were graded under a slit lamp. The protein concentrations and total number of cells in the aqueous humour (AqH) were examined, and the retinal expression of various inflammatory mediators was detected. The levels of nuclear factor-kappa B (NF-κB), phosphorylated NF-κB, IkappaB-a (IκB-a), phosphorylated IκB-a, IKK, phosphorylated IKK, PI3Kp85, phosphorylated PI3Kp85, Akt and phosphorylated Akt were evaluated by western blotting. Treatment with rhSlit2 dramatically diminished the clinical scores of EIU, with significant decreases in inflammatory cell infiltration, protein concentrations, cellulose-like exudates, the production of ICAM-1, MCP-1, TNF-α and IL-6 in the AqH; and adhesion of leucocytes. The PI3K/Akt/IKK/NF-κB pathway was found to be activated in EIU. However, the pre-treatment of rhSlit2 significantly inhibited the production of ICAM-1, MCP-1, TNF-α, and IL-6, and inhibited leucocyte adhesion by modulating the PI3K/Akt/IKK/NF-κB pathway. In conclusion, the intravitreal injection of rhSlit2 alleviated EIU-related inflammation in Sprague-Dawley rats by reducing the proinflammatory cytokines and leucocyte adhesion; in particular, rhSlit2 may inhibit LPS-induced inflammation by inhibiting the activation of PI3K/Akt/IKK/NF-κB signalling pathway. Therefore, rhSlit2 shows significant potential for effectively alleviating immune inflammatory responses in vivo.

Chaperonin-Containing TCP1 Subunit 5 Protects Against the Effect of Mer Receptor Tyrosine Kinase Knockdown in Retinal Pigment Epithelial Cells by Interacting With Filamentous Actin and Activating the LIM-Kinase 1/Cofilin Pathway.

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)-which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)-plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.

Multimode imaging characteristics and treatment of uveal schwannoma.

AIM: To delineate the different imaging characteristics of uveal schwannoma from melanoma and discuss the optimal treatment strategy for intraocular schwannoma. METHODS: Case series of three patients diagnosed with intraocular schwannoma was collected at Zhongshan Ophthalmic Center, Guangzhou, China from July 2014 to December 2020. All the study patients underwent ultrasonography and magnetic resonance imaging (MRI). The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. RESULTS: Ultrasonography of all three patients (all females, mean age, 39y, age range, 23-54y) showed low to medium reflectivity with a homogeneous internal structure. MRI of all three patients demonstrated isointensity on T1-weighted imaging spin-echo (T1WI SE) images and hypointense on fast spin-echo T2-weighted images (FSE T2WI) images with respect to the brain. Minimally invasive pars plana vitrectomy (PPV) and local resection of the tumor was performed for all patients, and the diagnosis of schwannoma was confirmed by histopathological examination. CONCLUSION: The present study indicates that ultrasonography and MRI features of uveal schwannoma may contribute to the differentiation of uveal schwannoma from melanoma, and the optimal therapy for intraocular schwannoma is minimally invasive PPV and local resection.

HMGB1 downregulation in retinal pigment epithelial cells protects against diabetic retinopathy through the autophagy-lysosome pathway.

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus and currently one of the major causes of blindness. Several previous studies have demonstrated that autophagy, which is regulated by HMGB1 (high mobility group box 1), is involved in DR development. However, the role of autophagy in DR is quite complicated in that it promotes pericyte survival in early DR, whereas excessive autophagy causes excess stress and leads to necrosis. Therefore, this study aimed to investigate the relationship between HMGB1, the macroautophagy/autophagy-lysosome pathway, and DR, as well as their underlying molecular mechanisms. In brief, the relationship between high glucose (HG) and the autophagy-lysosome pathway was examined in retinal pigment epithelial (RPE) cells. The relationship was studied by detecting classical autophagic features, and siRNAs targeting HMGB1 and pharmacological regulators were used to explore the role of the autophagy-lysosome pathway in DR development. The results demonstrated that HG inhibited autophagy and diminished the degradative capacity of autophagy due to lysosome membrane permeabilization (LMP). In addition, HMGB1 was found to be involved in LMP via the CTSB (cathepsin B)-dependent pathway, but not the CTSL (cathepsin L)-dependent pathway. Knockdown of HMGB1 expression rescued LMP, restored the degradative capacity of autophagy, decreased the expression of inflammatory factors and VEGF (vascular endothelial growth factor), and protected against apoptosis in RPE cells in the early stages of DR.

Intraoperative choroidal detachment during small-gauge vitrectomy: analysis of causes, anatomic, and visual outcomes.

INTRODUCTION: To investigate the incidence and causes of intraoperative choroidal detachment (CD) during small-gauge vitrectomy, as well as the anatomic and visual outcomes. METHODS: We retrospectively reviewed the medical records of 1026 consecutive patients who underwent small-gauge vitrectomy from June 2017 to December 2018 at Zhongshan Ophthalmic Centre, Guangzhou, China. Data on the presence, location, and extent of intraoperative CD and its relationship to the infusion cannula were collected. Patient demographic characteristics and postoperative anatomic and visual outcomes were also assessed. RESULTS: A total of six cases were found to have intraoperative CD, including two with serous CD, three with limited haemorrhagic CD, and one with CD caused by inadvertent perfusion of gas during air/fluid exchange. Retraction of the infusion cannula and acute ocular hypotony were found to be the main causes of intraoperative CD in five out of the six cases. The best-corrected visual acuity of all cases significantly improved after the surgery. CONCLUSION: The incidence of intraoperative CD during small-gauge vitrectomy is low; the predominant causes are retraction of the infusion cannula and acute ocular hypotony. Immediate awareness and timely closure of the incision may contribute to a better surgical prognosis.

Disulfiram Exerts Antiadipogenic, Anti-Inflammatory, and Antifibrotic Therapeutic Effects in an In Vitro Model of Graves' Orbitopathy.

Background: Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves' orbitopathy (GO). We hypothesized that disulfiram (DSF), an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism, would have therapeutic effects on orbital fibroblasts (OFs) in GO. This study aimed at determining the therapeutic effects and underlying mechanisms of DSF on these parameters. Methods: Primary cultures of OFs from six GO patients and six control subjects were established. The OFs were allowed to differentiate into adipocytes and treated with various concentrations of DSF. Lipid accumulation within the cells was evaluated by Oil Red O staining. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to measure the expression of key adipogenic transcription factors, ALDH1A1, ALDH2, and mitogen-activated protein kinase (MAPK) signaling proteins. Apoptosis assays and reactive oxygen species levels were evaluated by flow cytometry. HA production was measured by using an enzyme-linked immunosorbent assay (ELISA) kit. The mRNA levels of proinflammatory molecules were measured by using RT-PCR after interleukin (IL)-1ß stimulation with or without DSF. The mRNA expression of markers associated with fibrosis was examined by using RT-PCR after transforming growth factor (TGF)-ß1 stimulation with or without DSF. The wound-healing assay was assessed by phase-contrast microscopy. Results: Under identical adipogenesis conditions, GO OFs effectively differentiated, while normal control (NC) OFs did not. DSF dose dependently suppressed lipid accumulation during adipogenesis in GO OFs. The expression of key adipogenic transcription factors, such as perilipin-1 (PLIN1), PPARγ (PPARG), FABP4, and c/EBPα (CEBPA), was downregulated. Further, DSF inhibited the phosphorylation of ERK by inhibiting ALDH1A1. In addition, DSF attenuated HA production and suppressed inflammatory molecule expression induced by IL-1ß in GO OFs and NC OFs. The antifibrotic effects of DSF on TGF-ß1 were also observed in GO OFs. Conclusions: In the current study, we provide evidence of the inhibitory effect of DSF on GO OFs adipogenesis, HA production, inflammation, and fibrosis in vitro. The results of this study are noteworthy and indicate the potential use of DSF as a therapeutic agent for the treatment of GO.

Decreased microRNA-155 in Behcet's disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production.

BACKGROUND: Earlier, we reported that the microRNA (miR)-155 expression in dendritic cells (DCs) from Behcet's disease (BD) patients was decreased and affected cytokine production of DCs. In this study, we investigated the mechanisms whereby miR-155 regulates cytokine production by DCs. METHODS: The formation of autophagosomes in DCs was detected by transmission electron microscopy. Western blotting was used to detect the protein levels of LC3, Beclin-1, P62, p-mTOR, and p-Akt in DCs. TNF-α, IL-6, and IL-1ß expression were investigated by ELISA. MiR-155 mimics were transfected to DCs to evaluate its effects on autophagy and cytokine production. RNA interference was used to downregulate the expression of TAB2. RESULTS: The formation of autophagosomes was found in DCs of active BD patients. The expressions of LC3-II, Beclin-1, and P62 were significantly increased in DCs of active BD patients compared to that of inactive BD patients and healthy controls. The expressions of IL-6, IL-1ß, and TNF-α were significantly increased in DCs of active BD patients compared to that of healthy controls. The autophagy promoter (3-MA) and inhibitor (rapamycin) significantly decreased or increased the expression of TNF-α, IL-6, and IL-1ß by DCs. The expression of LC3-II and Beclin-1 was significantly increased, but the expression of P62 proteins was decreased in DCs transfected with miR-155 mimics or after TAB2 was downregulated. The expression of TNF-α, IL-6, and IL-1ß was decreased in DCs after miR-155 was upregulated or TAB2 was downregulated. The ratios of p-Akt/Akt and p-mTOR/mTOR were decreased in DCs after miR-155 was upregulated. CONCLUSIONS: These results suggest that miR-155 affects the production of TNF-α, IL-6, and IL-1ß by DCs through activation of the Akt/mTOR signaling pathway and by affecting the process of autophagy.

Rapid identification of tsunamigenic earthquakes using GNSS ionospheric sounding.

The largest tsunamis are generated by seafloor uplift resulting from rupture of offshore subduction-zone megathrusts. The rupture of the shallowest part of a megathrust often produces unexpected outsize tsunami relative to their seismic magnitude. These are so called 'tsunami earthquakes', which are difficult to identify rapidly using the current tsunami warning systems, even though, they produce some of the deadliest tsunami. We here introduce a new method to evaluate the tsunami risk by measuring ionospheric total electron content (TEC). We examine two Mw 7.8 earthquakes (one is a tsunami earthquake and the other is not) generated in 2010 by the Sunda megathrust, offshore Sumatra, to demonstrate for the first time that observations of ionospheric sounding from Global Navigation Satellite System (GNSS) can be used to evaluate the tsunamigenic potential of earthquakes as early as 8 min after the mainshock.

Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease.

Purpose: To investigate the role of G-protein-coupled bile acid receptor-1, Gpbar1 (TGR5) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.Methods: The mRNA level of TGR5, iNOS, Arg1, CD16, and CD206 in macrophages was assayed by real-time PCR. ELISA was used to detect the production of cytokines in cell culture supernatants. The frequencies of CD4+IFN-γ+ and CD4+ IL-17+ T cells were tested by flow cytometry.Results: A decreased expression of TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls. TGR5 stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 toward the anti-inflammatory M2 macrophage subtype. TGR5 activation of macrophages co-cultured with CD4+ T cells inhibited Th1 and Th17 polarization, as well as the release of IFN-γ and IL-17 in the culture supernatant.Conclusion: Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.

Transient rheology of the Sumatran mantle wedge revealed by a decade of great earthquakes.

Understanding the rheological properties of the upper mantle is essential to develop a consistent model of mantle dynamics and plate tectonics. However, the spatial distribution and temporal evolution of these properties remain unclear. Here, we infer the rheological properties of the asthenosphere across multiple great megathrust earthquakes between 2004 and 2014 along the Sumatran subduction zone, taking advantage of decade-long continuous GPS and tide-gauge measurements. We observe transient mantle wedge flow following these earthquakes, and infer the temporal evolution of the effective viscosity. We show that the evolution of stress and strain rate following these earthquakes is better matched by a bi-viscous than by a power-law rheology model, and we estimate laterally heterogeneous transient and background viscosities on the order of ~1017 and ~1019 Pa s, respectively. Our results constitute a preliminary rheological model to explain stress evolution within earthquake cycles and the development of seismic hazard in the region.

Imaging the distribution of transient viscosity after the 2016 Mw 7.1 Kumamoto earthquake.

The deformation of mantle and crustal rocks in response to stress plays a crucial role in the distribution of seismic and volcanic hazards, controlling tectonic processes ranging from continental drift to earthquake triggering. However, the spatial variation of these dynamic properties is poorly understood as they are difficult to measure. We exploited the large stress perturbation incurred by the 2016 earthquake sequence in Kumamoto, Japan, to directly image localized and distributed deformation. The earthquakes illuminated distinct regions of low effective viscosity in the lower crust, notably beneath the Mount Aso and Mount Kuju volcanoes, surrounded by larger-scale variations of viscosity across the back-arc. This study demonstrates a new potential for geodesy to directly probe rock rheology in situ across many spatial and temporal scales.

Asthenosphere rheology inferred from observations of the 2012 Indian Ocean earthquake.

The concept of a weak asthenospheric layer underlying Earth's mobile tectonic plates is fundamental to our understanding of mantle convection and plate tectonics. However, little is known about the mechanical properties of the asthenosphere (the part of the upper mantle below the lithosphere) underlying the oceanic crust, which covers about 60 per cent of Earth's surface. Great earthquakes cause large coseismic crustal deformation in areas hundreds of kilometres away from and below the rupture area. Subsequent relaxation of the earthquake-induced stresses in the viscoelastic upper mantle leads to prolonged postseismic crustal deformation that may last several decades and can be recorded with geodetic methods. The observed postseismic deformation helps us to understand the rheological properties of the upper mantle, but so far such measurements have been limited to continental-plate boundary zones. Here we consider the postseismic deformation of the very large (moment magnitude 8.6) 2012 Indian Ocean earthquake to provide by far the most direct constraint on the structure of oceanic mantle rheology. In the first three years after the Indian Ocean earthquake, 37 continuous Global Navigation Satellite Systems stations in the region underwent horizontal northeastward displacements of up to 17 centimetres in a direction similar to that of the coseismic offsets. However, a few stations close to the rupture area that had experienced subsidence of up to about 4 centimetres during the earthquake rose by nearly 7 centimetres after the earthquake. Our three-dimensional viscoelastic finite-element models of the post-earthquake deformation show that a thin (30-200 kilometres), low-viscosity (having a steady-state Maxwell viscosity of (0.5-10) × 1018 pascal seconds) asthenospheric layer beneath the elastic oceanic lithosphere is required to produce the observed postseismic uplift.

Upper-mantle water stratification inferred from observations of the 2012 Indian Ocean earthquake.

Water, the most abundant volatile in Earth's interior, preserves the young surface of our planet by catalysing mantle convection, lubricating plate tectonics and feeding arc volcanism. Since planetary accretion, water has been exchanged between the hydrosphere and the geosphere, but its depth distribution in the mantle remains elusive. Water drastically reduces the strength of olivine and this effect can be exploited to estimate the water content of olivine from the mechanical response of the asthenosphere to stress perturbations such as the ones following large earthquakes. Here, we exploit the sensitivity to water of the strength of olivine, the weakest and most abundant mineral in the upper mantle, and observations of the exceptionally large (moment magnitude 8.6) 2012 Indian Ocean earthquake to constrain the stratification of water content in the upper mantle. Taking into account a wide range of temperature conditions and the transient creep of olivine, we explain the transient deformation in the aftermath of the earthquake that was recorded by continuous geodetic stations along Sumatra as the result of water- and stress-activated creep of olivine. This implies a minimum water content of about 0.01 per cent by weight-or 1,600 H atoms per million Si atoms-in the asthenosphere (the part of the upper mantle below the lithosphere). The earthquake ruptured conjugate faults down to great depths, compatible with dry olivine in the oceanic lithosphere. We attribute the steep rheological contrast to dehydration across the lithosphere-asthenosphere boundary, presumably by buoyant melt migration to form the oceanic crust.