Centre for Eye Research Australia (CERA) - Research Publications

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    Multi-focal electro-retinogram response following sub-threshold nano-second laser intervention in age-related macular degeneration
    Luu, CD ; Makeyeva, G ; Caruso, E ; Baglin, E ; Sivarajah, P ; Wu, Z ; Guymer, RH (WILEY, 2020-09)
    IMPORTANCE: The effect of sub-threshold nano-second laser (SNL) treatment on retinal function remains unknown. BACKGROUND: SNL treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the longitudinal effect of SNL treatment on retinal function. DESIGN: This was a sub-study of the LEAD trial; a 36-month, multi-centre, randomized and sham-controlled trial. PARTICIPANTS: Subjects with iAMD. METHODS: Eligible participants were assigned randomly to receive SNL or sham treatment to the study eye at 6-monthly visits. Multi-focal electro-retinography (mfERG) was performed at each study visit from a study site. The mfERG responses were grouped into three regions (central, middle and outer rings) and compared between the SNL and sham group. MAIN OUTCOME MEASURES: mfERG P1 response amplitude and implicit time. RESULTS: Data were collected from 50 subjects (26 in the SNL group, 24 in the sham group). At baseline, the P1 amplitudes of both the study eyes and the fellow eyes were similar between the groups at all rings. In the sham group, the P1 amplitude gradually decreased over time (P < .05). In the SNL group, there was an improvement in P1 amplitude which became statistically significant at the 36-month visit, detected in both the treated and fellow eyes at the central (P = .005) and middle ring (P = .007) but not at the outer ring (P = .070). No difference in P1 implicit time detected between the groups (P > .05). CONCLUSIONS AND RELEVANCE: SNL treatment improved electro-physiological function. mfERG could be useful for monitoring AMD progression and evaluating the efficacy of SNL treatment.
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    The linear ubiquitin chain assembly complex: a new function in thymic T cell differentiation and regulatory T cell homeostasis
    Teh, C ; Lalaoui, N ; Jain, R ; Policheni, A ; Heinlein, M ; Alvarez-Diaz, S ; Rieser, E ; Deuser, S ; Koay, H-F ; Hu, Y ; Kupresanin, F ; O'Reilly, L ; Godfrey, D ; Smyth, G ; Bouillet, P ; Strasser, A ; Walczak, H ; Silke, J ; Gray, D (WILEY-BLACKWELL, 2016-08)
    The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3+ regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation.
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    Long-term effects of homelessness on mortality: a 15-year Australian cohort study
    Seastres, RJ ; Hutton, J ; Zordan, R ; Moore, G ; Mackelprang, J ; Kiburg, KV ; Sundararajan, V (WILEY, 2020-12)
    OBJECTIVE: To examine the effect of homelessness on mortality. METHODS: This 15-year retrospective longitudinal cohort study compared mortality outcomes of homeless and non-homeless adults attending the emergency department of an inner-city public hospital in Melbourne, Victoria between 1 January 2003 and 31 December 2004. Homeless individuals had ≥1 recorded episodes of homelessness within the recruitment period, categorised by type: primary, secondary, tertiary, marginally housed. Non-homeless individuals were stably housed throughout. RESULTS: Over 15 years, homeless individuals had a higher mortality rate (11.89 vs. 8.10 per 1,000 person-years), significantly increased mortality risk (rate ratio 1.47, 95% confidence interval [CI] 1.26-1.71) and younger median age at death (66.60 vs. 78.19 years) compared to non-homeless individuals. Using adjusted Cox proportional hazards models, primary (hazard ratio [HR] 2.05, 95%CI 1.67-2.50), secondary (HR 1.60, 95%CI 1.23-2.10) and tertiary (HR 1.72, 95%CI 1.16-2.56) homelessness were independent risk factors for premature mortality. CONCLUSION: At least one recorded episode of primary, secondary, or tertiary homelessness was associated with premature mortality and younger age at death over a 15-year period. Implications for public health: Accurately identifying individuals experiencing primary, secondary or tertiary homelessness at the emergency department may enable targeted interventions that could potentially reduce their risk of premature mortality.