The susceptibility of human CD4⁺ and CD8⁺ T cells to senesce differs, with CD8⁺ T cells acquiring an immunosenescent phenotype faster than the CD4⁺ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4⁺ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8⁺ T cells has knock‐on consequences for nutrient usage, metabolism and function. Senescent CD4⁺ T cells uptake more lipid and glucose than their CD8⁺ counterparts, leading to a greater metabolic versatility engaging either an oxidative or a glycolytic metabolism. The enhanced metabolic advantage of senescent CD4⁺ T cells allows for more proliferation and migration than observed in the senescent CD8⁺ subset. Mitochondrial dysfunction has been linked to both cellular senescence and aging; however, it is still unclear whether mitochondria play a causal role in senescence. Our data show that reducing mitochondrial function in human CD4⁺ T cells, through the addition of low‐dose rotenone, causes the generation of a CD4⁺ T cell with a CD8⁺‐like phenotype. Therefore, we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype.

The impact of cellular senescence during ageing is well established, however senescence is now recognised to play a role in a variety of age related and metabolic diseases, such as cancer, autoimmune and cardiovascular diseases. It is therefore crucial to gain a better understanding of the mechanisms that control cellular senescence. In recent years our understanding of the intimate relationship between cell metabolism, cell signalling and cellular senescence has greatly improved. In this review we discuss the differing roles of glucose and protein metabolism in both senescent fibroblast and CD8+ T-cells, and explore the impact cellular metabolism has on the senescence-associated secretory phenotype (SASP) of these cell types.

Purpose: Avacopan is a novel C5a receptor inhibitor which was recently licensed for treatment of severe granulomatosis with polyangiitis (GPA) in the European Union and the United Kingdom. To the best of our knowledge, this is the first described case on initial ophthalmic outcomes in a patient with severe GPA and concurrent refractory scleritis treated with avacopan. Case Description: We present a case of de novo scleritis in a 77-year-old male with a background of retinitis pigmentosa with Argus II implant in situ. Severe scleral inflammation occurred following a suture removal from the implant site. Remission was not maintained despite orbital floor injections and high dose oral prednisolone. The diagnostic work-up revealed GPA which quickly progressed to involve vital organs. In view of his systemic deterioration, he was started on avacopan alongside rituximab, cyclophosphamide and high dose oral prednisolone. Sustained remission of scleritis was noted after 7 months of treatment with avacopan and low dose oral prednisolone with no other maintenance immunosuppression. Conclusion: We observed a sustained benefit of avacopan in allowing for successful taper of systemic steroids. We report that avacopan used alongside other immunosuppressants may be a viable option in patients with GPA and concurrent refractory scleritis. Further studies are needed to establish the longer term impact of this agent on the control of scleral inflammation.

Diabetic retinopathy (DR) is a major cause of preventable blindness in working-age adults, yet the molecular mechanisms behind its vision-threatening complications remain not fully understood. Transcriptomics enables the study of these processes through active gene expression, providing a pathway to the discovery of new biomarkers and therapeutic targets. Vitreous humour is commonly affected in numerous retinal pathologies, including DR, and is accessible through pars plana vitrectomy, making it a good candidate for transcriptomics research. Following PubMed and Embase search, 18 articles on vitreous transcriptomics were included. They were subclassified into themes of non-coding RNA, RNA methylation, angiogenesis, inflammation and fibrosis. We concluded that vitreous transcriptomics has the potential to influence future DR diagnostics and therapeutics. However, current evidence is limited by underpowered studies and lack of standardised protocols.