SUMMARYThe diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch. Functional studies of targets, such as klumpfuss (ERG/WT1 family) and pebbled/hindsight (RREB1 homologue), show that Notch acts both to prevent the cells adopting alternate cell fates and to promote morphological characteristics associated with crystal cell differentiation. Inappropriate activity of Klumpfuss perturbs the differentiation programme, resulting in melanotic tumours. Thus, by acting as a master regulator, Lz directs Notch to activate selectively a combination of target genes that correctly locks cells into the differentiation programme.

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Lumbar puncture in ocular syphilis patients should continue to be a routine part of the investigation of these patients; a large proportion of ocular syphilis patients show cerebrospinal fluid findings suggestive of neurosyphilis, are at risk of the complications of neurosyphilis, and should be managed accordingly.

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the “steady state” on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases.

Day 1 review detected adverse events in 0.5% of study patients. No long-term complications were reported in the 22% of patients who received treatment for early postoperative IOP elevation. This observation has led to the removal of routine day 1 review from the surgical care pathway following routine uncomplicated vitrectomy at the study institution.

Purpose: To review the outcomes of pars plana vitrectomy, internal limiting membrane (ILM) peel, and gas tamponade in the management of traumatic paediatric macular holes. Methods: Retrospective case series of children undergoing vitrectomy, ILM peel, and gas tamponade for traumatic macular hole between March 2007 and July 2014. Main outcome measures were postoperative visual acuity at 3 and 12 months, anatomic closure rate, and surgical complications. Results: Anatomic macular hole closure was achieved in 12 (92.3%) of 13 cases. Mean preoperative logMAR visual acuity was 0.91 (95% CI 0.65-1.17) with improvement postoperatively to 0.54 (95% CI 0.43-0.64) at 3 months (p = 0.002) and 0.50 (95% CI 0.39-0.60) at 12 months (p = 0.002). There were no perioperative complications. Conclusion: Pars plana vitrectomy and ILM peel is an effective management option for paediatric macular holes.

This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome.

Fibrotic conditions are a significant global disease burden. While some therapies delay disease progression, none reverse fibrosis. To gain insights into how fibrosis might resolve, we developed a comparative single cell atlas of frozen shoulder capsule tissue; a chronic inflammatory fibrotic human disease that resolves spontaneously. We identified both a population of pro-inflammatory MERTKlowCD48+ macrophages (Mφ) and a population of MERTK+LYVE1+MRC1+Mφ enriched for negative regulators of inflammation. Micro-cultures of patient-derived cells identified cell-matrix interactions between MERTK+Mφ and DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in the resolution of frozen shoulder. Cross-tissue analysis revealed a shared gene expression cassette between MERTK+Mφ in the shoulder capsule and a similar cell population enriched in synovial tissues from rheumatoid arthritis patients in disease remi ssion, supporting the concept that MERTK+Mφ provide a cellular basis for the resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identified MERTK+LYVE1+MRC1+Mφ and DKK3+ and POSTN+ fibroblast populations analogous to those identified in adult shoulder capsule, suggesting that the template to resolve fibrosis is established during development. Therapeutic enhancement of crosstalk between MerTK+Mφ and pro-resolving DKK3+ and POSTN+ fibroblasts could accelerate resolution of frozen shoulder and resolve persistent inflammatory fibrotic disease in other tissues.