The impact of childhood glaucoma on psychosocial functioning and quality of life: a review of the literature

We present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL

A dual function of SnRK2 kinases in the regulation of SnRK1 and plant growth

[EN] Adverse environmental conditions trigger responses in plants that promote stress tolerance and survival at the expense of growth(1). However, little is known of how stress signalling pathways interact with each other and with growth regulatory components to balance growth and stress responses. Here, we show that plant growth is largely regulated by the interplay between the evolutionarily conserved energy-sensing SNF1-related protein kinase 1 (SnRK1) protein kinase and the abscisic acid (ABA) phytohormone pathway. While SnRK2 kinases are main drivers of ABA-triggered stress responses, we uncover an unexpected growth-promoting function of these kinases in the absence of ABA as repressors of SnRK1. Sequestration of SnRK1 by SnRK2-containing complexes inhibits SnRK1 signalling, thereby allowing target of rapamycin (TOR) activity and growth under optimal conditions. On the other hand, these complexes are essential for releasing and activating SnRK1 in response to ABA, leading to the inhibition of TOR and growth under stress. This dual regulation of SnRK1 by SnRK2 kinases couples growth control with environmental factors typical for the terrestrial habitat and is likely to have been critical for the water-to-land transition of plants.We thank J.-K. Zhu for the snrk2 mutants, M. Bennett for the SnRK2.2-GFP line, C. Koncz for the SnRK1-GFP line, X. Li for the SnRK2.3-FLAG OE line, J. Schroeder for the GFP-His-FLAG and SnRK2.6-His-FLAG OE lines, C. Mackintosh for the TPS5 antibody and the Nottingham Arabidopsis stock centre for T-DNA mutant seeds. The IGC Plant Facility (Vera Nunes) is thanked for excellent plant care. This work was supported by Fundacao para a Ciencia e a Tecnologia through the R&D Units UIDB/04551/2020 (GREEN-IT-Bioresources for Sustainability) and UID/MAR/04292/2019, FCT project nos. PTDC/BIA-PLA/7143/2014, LISBOA-01-0145-FEDER-028128 and PTDC/BIA-BID/32347/2017, and FCT fellowships/contract nos. SFRH/BD/122736/2016 (M.A.), SFRH/BPD/109336/2015 (A.C.), PD/BD/150239/2019 (D.R.B.), and IF/00804/2013 (E.B.G.). Work in P.L.R.'s laboratory was funded by MCIU grant no. BIO2017-82503-R. C.M. thanks the LabEx Paris Saclay Plant Sciences-SPS (ANR-10-LABX-040-SPS) for support. B.B.P. was funded by Programa VALi+d GVA APOSTD/2017/039. This project has received funding from the European Union Horizon 2020 research and innovation programme (grant agreement no. 867426-ABA-GrowthBalance-H2020-WF-2018-2020/H2020-WF-01-2018, awarded to B.B.P.). This work is dedicated to the memory of our beloved friend and colleague Americo Rodrigues.Belda-Palazón, B.; Adamo, M.; Valerio, C.; Ferreira, LJ.; Confraria, A.; Reis-Barata, D.; Rodrigues, A.... (2020). A dual function of SnRK2 kinases in the regulation of SnRK1 and plant growth. Nature Plants (Online). 6(11):1345-1353. https://doi.org/10.1038/s41477-020-00778-wS13451353611Huot, B., Yao, J., Montgomery, B. L. & He, S. Y. Growth-defense tradeoffs in plants: a balancing act to optimize fitness. Mol. Plant 7, 1267–1287 (2014).Baena-Gonzalez, E., Rolland, F., Thevelein, J. M. & Sheen, J. A central integrator of transcription networks in plant stress and energy signalling. Nature 448, 938–942 (2007).Baena-Gonzalez, E. & Sheen, J. Convergent energy and stress signaling. Trends Plant Sci. 13, 474–482 (2008).Nukarinen, E. et al. Quantitative phosphoproteomics reveals the role of the AMPK plant ortholog SnRK1 as a metabolic master regulator under energy deprivation. Sci. Rep. 6, 31697 (2016).Rodrigues, A. et al. ABI1 and PP2CA phosphatases are negative regulators of Snf1-related protein kinase1 signaling in Arabidopsis. Plant Cell 25, 3871–3884 (2013).Nakashima, K., Yamaguchi-Shinozaki, K. & Shinozaki, K. The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat. Front. Plant Sci. 5, 170 (2014).Fujii, H., Verslues, P. E. & Zhu, J. K. Identification of two protein kinases required for abscisic acid regulation of seed germination, root growth, and gene expression in Arabidopsis. Plant Cell 19, 485–494 (2007).Mustilli, A. C., Merlot, S., Vavasseur, A., Fenzi, F. & Giraudat, J. Arabidopsis OST1 protein kinase mediates the regulation of stomatal aperture by abscisic acid and acts upstream of reactive oxygen species production. Plant Cell 14, 3089–3099 (2002).Umezawa, T. et al. Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis. Proc. Natl Acad. Sci. USA 106, 17588–17593 (2009).Vlad, F. et al. Protein phosphatases 2C regulate the activation of the Snf1-related kinase OST1 by abscisic acid in Arabidopsis. Plant Cell 21, 3170–3184 (2009).Yoshida, R. et al. The regulatory domain of SRK2E/OST1/SnRK2.6 interacts with ABI1 and integrates abscisic acid (ABA) and osmotic stress signals controlling stomatal closure in Arabidopsis. J. Biol. Chem. 281, 5310–5318 (2006).Ma, Y. et al. Regulators of PP2C phosphatase activity function as abscisic acid sensors. Science 324, 1064–1068 (2009).Park, S. Y. et al. Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins. Science 324, 1068–1071 (2009).Bitrian, M., Roodbarkelari, F., Horvath, M. & Koncz, C. BAC-recombineering for studying plant gene regulation: developmental control and cellular localization of SnRK1 kinase subunits. Plant J. 65, 829–842 (2011).Jossier, M. et al. SnRK1 (SNF1-related kinase 1) has a central role in sugar and ABA signalling in Arabidopsis thaliana. Plant J. 59, 316–328 (2009).Lin, C. R. et al. SnRK1A-interacting negative regulators modulate the nutrient starvation signaling sensor SnRK1 in source-sink communication in cereal seedlings under abiotic stress. Plant Cell 26, 808–27 (2014).Lu, C. A. et al. The SnRK1A protein kinase plays a key role in sugar signaling during germination and seedling growth of rice. Plant Cell 19, 2484–2499 (2007).Radchuk, R. et al. Sucrose non-fermenting kinase 1 (SnRK1) coordinates metabolic and hormonal signals during pea cotyledon growth and differentiation. Plant J. 61, 324–338 (2010).Radchuk, R., Radchuk, V., Weschke, W., Borisjuk, L. & Weber, H. Repressing the expression of the SUCROSE NONFERMENTING-1-RELATED PROTEIN KINASE gene in pea embryo causes pleiotropic defects of maturation similar to an abscisic acid-insensitive phenotype. Plant Physiol. 140, 263–278 (2006).Tsai, A. Y. & Gazzarrini, S. AKIN10 and FUSCA3 interact to control lateral organ development and phase transitions in Arabidopsis. Plant J. 69, 809–821 (2012).Tsai, A. Y. & Gazzarrini, S. Trehalose-6-phosphate and SnRK1 kinases in plant development and signaling: the emerging picture. Front. Plant Sci. 5, 119 (2014).Zhang, Y. et al. Arabidopsis sucrose non-fermenting-1-related protein kinase-1 and calcium-dependent protein kinase phosphorylate conserved target sites in ABA response element binding proteins. Ann. Appl. Biol. 153, 401–409 (2008).Ramon, M. et al. Default activation and nuclear translocation of the plant cellular energy sensor SnRK1 regulate metabolic stress responses and development. Plant Cell 31, 1614–1632 (2019).Lopez-Molina, L., Mongrand, S. & Chua, N. H. A postgermination developmental arrest checkpoint is mediated by abscisic acid and requires the ABI5 transcription factor in Arabidopsis. Proc. Natl Acad. Sci. USA 98, 4782–4787 (2001).Garcia, D. & Shaw, R. J. AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol. Cell 66, 789–800 (2017).Dobrenel, T. et al. The Arabidopsis TOR kinase specifically regulates the expression of nuclear genes coding for plastidic ribosomal proteins and the phosphorylation of the cytosolic ribosomal protein S6. Front. Plant Sci. 7, 1611 (2016).Wang, P. et al. Reciprocal regulation of the TOR kinase and ABA receptor balances plant growth and stress response. Mol. Cell 69, 100–112 e106 (2018).Van Leene, J. et al. Capturing the phosphorylation and protein interaction landscape of the plant TOR kinase. Nat. Plants 5, 316–327 (2019).Dietrich, D. et al. Root hydrotropism is controlled via a cortex-specific growth mechanism. Nat. Plants 3, 17057 (2017).Wu, Q. et al. Ubiquitin ligases RGLG1 and RGLG5 regulate abscisic acid signaling by controlling the turnover of phosphatase PP2CA. Plant Cell 28, 2178–2196 (2016).Belin, C. et al. Identification of features regulating OST1 kinase activity and OST1 function in guard cells. Plant Physiol. 141, 1316–1327 (2006).Fujii, H. & Zhu, J. K. Arabidopsis mutant deficient in 3 abscisic acid-activated protein kinases reveals critical roles in growth, reproduction, and stress. Proc. Natl Acad. Sci. USA 106, 8380–8385 (2009).Fujita, Y. et al. Three SnRK2 protein kinases are the main positive regulators of abscisic acid signaling in response to water stress in Arabidopsis. Plant Cell Physiol. 50, 2123–2132 (2009).Nakashima, K. et al. Three Arabidopsis SnRK2 protein kinases, SRK2D/SnRK2.2, SRK2E/SnRK2.6/OST1 and SRK2I/SnRK2.3, involved in ABA signaling are essential for the control of seed development and dormancy. Plant Cell Physiol. 50, 1345–1363 (2009).Fujii, H. et al. In vitro reconstitution of an abscisic acid signalling pathway. Nature 462, 660–664 (2009).Shen, W., Reyes, M. I. & Hanley-Bowdoin, L. Arabidopsis protein kinases GRIK1 and GRIK2 specifically activate SnRK1 by phosphorylating its activation loop. Plant Physiol. 150, 996–1005 (2009).Cheng, C. et al. SCFAtPP2-B11 modulates ABA signaling by facilitating SnRK2.3 degradation in Arabidopsis thaliana. PLoS Genet. 13, e1006947 (2017).Harthill, J. E. et al. Phosphorylation and 14-3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose. Plant J. 47, 211–223 (2006).Song, Y. et al. Identification of novel interactors and potential phosphorylation substrates of GsSnRK1 from wild soybean (Glycine soja). Plant Cell Environ. 42, 145–157 (2018).Wang, X., Du, Y. & Yu, D. Trehalose phosphate synthase 5-dependent trehalose metabolism modulates basal defense responses in Arabidopsis thaliana. J. Integr. Plant Biol. 61, 509–527 (2019).Broeckx, T., Hulsmans, S. & Rolland, F. The plant energy sensor: evolutionary conservation and divergence of SnRK1 structure, regulation, and function. J. Exp. Bot. 67, 6215–6252 (2016).Wang, Y. et al. AKINbeta1, a subunit of SnRK1, regulates organic acid metabolism and acts as a global modulator of genes involved in carbon, lipid, and nitrogen metabolism. J. Exp. Bot. 71, 1010–1028 (2020).Yoshida, T. et al. The role of abscisic acid signaling in maintaining the metabolic balance required for Arabidopsis growth under nonstress conditions. Plant Cell 31, 84–105 (2019).Zheng, Z. et al. The protein kinase SnRK2.6 mediates the regulation of sucrose metabolism and plant growth in Arabidopsis. Plant Physiol. 153, 99–113 (2010).Cutler, S. R., Rodriguez, P. L., Finkelstein, R. R. & Abrams, S. R. Abscisic acid: emergence of a core signaling network. Annu Rev. Plant Biol. 61, 651–679 (2010).Kravchenko, A. et al. Mutations in the Arabidopsis Lst8 and Raptor genes encoding partners of the TOR complex, or inhibition of TOR activity decrease abscisic acid (ABA) synthesis. Biochem. Biophys. Res. Commun. 467, 992–997 (2015).Salem, M. A., Li, Y., Wiszniewski, A. & Giavalisco, P. Regulatory-associated protein of TOR (RAPTOR) alters the hormonal and metabolic composition of Arabidopsis seeds, controlling seed morphology, viability and germination potential. Plant J. 92, 525–545 (2017).Bakshi, A. et al. Ectopic expression of Arabidopsis target of rapamycin (AtTOR) improves water-use efficiency and yield potential in rice. Sci. Rep. 7, 42835 (2017).De Smet, I. et al. An abscisic acid-sensitive checkpoint in lateral root development of Arabidopsis. Plant J. 33, 543–555 (2003).Hrabak, E. M. et al. The Arabidopsis CDPK-SnRK superfamily of protein kinases. Plant Physiol. 132, 666–680 (2003).Hauser, F., Waadt, R. & Schroeder, J. I. Evolution of abscisic acid synthesis and signaling mechanisms. Curr. Biol. 21, R346–R355 (2011).Umezawa, T. et al. Molecular basis of the core regulatory network in ABA responses: sensing, signaling and transport. Plant Cell Physiol. 51, 1821–1839 (2010)

Comparación del tonómetro de Goldmann, neumotonómetro de contacto y el efecto del grosor corneal

Comparar la medición de la presión intraocular (PIO) usando el tonómetro de aplanación de Goldmann (GAT) y el neumotonómetro de contacto (NTC), y evaluar el efecto del grosor corneal central (CCT) en las mediciones. Estudio prospectivo, clínico observacional. Se incluyeron 96 ojos de 49 pacientes 40 glaucomatosos, 29 hipertensos oculares y 27 controles. La PIO se midió con cada uno de los tonómetros. Además se midió el CCT. Se observó un coeficiente de correlación fuerte entre GAT y el NTC (Pearson = 0,922, p < 0,001). La media de las diferencias pareadas entre GAT y el NTC fue de 0,72 ± 2,82 mmHg. La media de las diferencias entre GAT y el NTC fue menor a valores bajos de PIO y más alta a valores mayores de PIO. Las mediciones con GAT demostraron un aumento medio de la PIO de 0,47 mmHg por cada 10 μm de CCT, y el NTC 0,34 mmHg por cada 10 μm, aunque la diferencia no fue estadísticamente significativa. La neumotonometría de contacto es un método fiable en el diagnóstico y seguimiento de nuestra población. El efecto del CCT fue mayor para el tonómetro de Goldmann. To compare the intraocular pressure (IOP) measurements using the Goldmann applanation tonometer (GAT) and contact pneumotonometer (NTC), and to evaluate the effects of central corneal thickness (CCT) on the readings. This was a prospective, observational clinical study, which included 96 eyes of 49 patients, 40 glaucomatous, 29 ocular hypertensive and 27 normal subjects. The IOP measurements were performed with each tonometer. The CCT was also measured. A strong correlation coefficient between GAT and the NTC was found (Pearson = 0.922, p < 0.001). The mean of paired differences between GAT and NTC was 0.72 ± 2.82 mmHg. The mean difference between GAT and NTC was low at lower levels of PIO and higher at higher levels of IOP. Readings with the GAT showed a mean increase in IOP of 0.47 mmHg for every 10 μm of CCT, and the NTC 0.34 mmHg for every 10 μm, the diference was not statistically significant. The contact pneumotonometer is a reliable method in diagnosis and follow up of our population. The effect of the central corneal thickness was more important for the Goldmann applanation tonometer

Retinal Infarcts in a Patient with an Acute Confusional Syndrome

A 46-year-old man presented with acute confusional syndrome, ataxia, dysarthria, and right hemiparesthesia. Brain MRI showed small bilateral infarcts and fluorescein angiography revealed multiple peripheral retinal infarcts bilaterally. No visual loss was present, and no other organs were involved. The diagnosis of Susac syndrome (microangiopathy of the brain, retina and cochlea) was made and immunosuppressive therapy begun

A Novel Technique for Anterior Segment Imaging Using B-scan Ultrasonography When Ultrasound Biomicroscopy Is Unavailable

Ultrasound biomicroscopy offers high-resolution images of anterior segment anatomy, essential for determining surgical intervention in special circumstances, yet is sometimes unavailable. The authors describe a novel technique to obtain gross anterior segment visualization using a commonly available instrument, B-scan ultrasonography, and compare it to ultrasound biomicroscopy imaging from two pediatric cases

Placement and Extension of Glaucoma Drainage Devices Using Polypropylene Suture in Pediatric Patients

Glaucoma drainage device tube placement and extension in pediatric patients may be complicated by abnormal anterior segment anatomy and corneal opacities. The authors describe two techniques for placement and extension of non-valved glaucoma drainage device tubes using polypropylene suture as a guidewire and stabilizer, respectively

Pathological findings in the lens capsules and intraocular lens in chronic pseudophakic endophthalmitis: An electron microscopy study

Purpose The aim of this study was to describe the pathological findings in lens capsules and intraocular lens (IOL) studied by scanning and/or transmission electron microscopy (SEM and TEM, respectively) in a series of four eyes with chronic pseudophakic endophthalmitis (CPE). Patients and methods We performed a retrospective study of four patients presenting CPE in whom surgical treatment with pars plana vitrectomy, capsulectomy with extraction of the IOL, and intravitreous antibiotic therapy was thereafter performed. The extracted IOL and the capsular remains were studied by SEM and/or TEM and microbiologic analysis of aqueous humour and vitreous aspirate was also carried out in all the cases. Results The presence of microorganisms was observed in the material analysed in all the cases studied. The use of TEM identified bacterial contamination by Staphylococcus spp and mixed contamination with microorganisms presenting a bacillar morphology suggestive of infection by Propionibacterium acnes in addition to the presence of cocci in the capsular remains. In another two cases, SEM localized colonies of Staphylococcus spp on the surface of the IOL in one case and mixed bacterial colonization with cocci plus filamentous bacteria in the other. The presence of macrophages associated with bacteria was observed in the capsular remains. Conclusions Microorganisms were found in the IOL or the capsular material in the four cases studied, thereby explaining the refractoriness and severity of infection. The possible presence of polymicrobial infections, especially in the cases with filamentous bacteria, also explains the recurrence of infection

The impact of childhood glaucoma on psychosocial functioning and quality of life: a review of the literature

We present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL