Objective: To study the protective effects of siponimod on the retina in experimental glaucoma model.

Background: Siponimod is indicated for the treatment of relapsing forms of multiple sclerosis (MS). Selective modulation of the sphingosine 1-phosphate receptor on lymphocytes by siponimod prevents their infiltration into the CNS and thereby functions through an anti-inflammatory mechanism. Apart from its immunosuppressive actions, siponimod is suggested to activate neuroprotective cellular signalling pathways. Chronic optic nerve injury in the form of experimental glaucoma leads to progressive loss of retinal ganglion cells and anterograde trans-synaptic degenerative changes in the higher visual centres. This study aimed to determine the potential protective effects of the drug on the retina in glaucoma conditions.

Methods: Intracameral microbead injections (Fluospheres, 10 µm, weekly) were performed into the anterior eye chamber of C57BL/6 mice that resulted in sustainably increased intraocular pressure (IOP) for 2 months (20-25 mmHg). Siponimod was administered through diet (10mg/kg) to a group of high IOP mice. Inner retinal functional assessment was performed using positive scotopic threshold responses (pSTRs, −4.3 log cd·s/m²) and amplitudes measured 100-120 ms after the initial stimulation. Histological analysis was performed in the retinal sections using hematoxylin and eosin staining.

Results: Mice fed on siponimod diet revealed 4-fold decrease in circulating lymphocytes counts compared to the control diet. No remarkable changes in biochemical analytes were detected in the serum of drug treated animals. Retinal pSTR confirmed that inner retinal function in glaucomatous eyes was decreased in glaucoma conditions. Drug treated animals demonstrated significant (p< 0.001) protection of about 61±6 % in pSTR amplitudes compared to the control high IOP exposed eyes. Histological assessment further supported these findings and revealed preservation of the ganglion cell layer in the siponimod treated group (p< 0.001).

Conclusion: We report that siponimod exhibited a protective effect on retinal electrophysiology and preserved inner retinal structure in experimental glaucoma. Our ongoing investigations will reveal potential biochemical mechanisms underlying these effects in the retina.

Disclosure: The authors have nothing to disclose. This study was supported by Novartis Australia.

Eating a plant-rich diet is considered essential for human and planetary health and the Mediterranean diet offers a realistic way to increase this. Gaining greater knowledge of the barriers and drivers to consuming the Mediterranean diet in residents of high-income countries was the aim of the current study. Semi-structured interviews were conducted with 16 adults residing in Australia who ate either an omnivore or plant-rich diet. Using reflexive thematic analysis (RTA) and the behaviour change wheel (BCW), an in-depth exploration of these barriers and drivers was conducted. Key barriers were: (1) changing ingrained meat habits, (2) lack of physical and mental availability, (3) household influences, (4) meat perceived as tasty and Mediterranean diet foods as bland and (5) minimal knowledge of the nutritional benefits of Mediterranean diet foods. Our findings emphasize the need to consider multiple individual and environmental barriers when designing behaviour change interventions to increase Mediterranean diet adoption.

Drug discovery is a process of recognizing the chemical moieties having the potential to serve as drugs. It involves the higher cost, low efficacy, and increased timelines for discovering a drug which have made it a complex process. Hence, there is an urge need of advancement in drug discovery process which can provide the revolutionary changes. In recent years, deep learning bears promise in the process of drug discovery. Deep learning plays a crucial role in various drug discovery processes namely drug monitoring, peptide synthesis, legend-based virtual screening, toxicity prediction, pharmacophore modeling, quantitative structural–activity relationship (QSAR), poly-pharmacology, drug repositioning, and physiochemical activities. This chapter presents an outline of these expanding topics related to drug discovery, the key concepts of prevalent deep learning algorithms, and motivation to investigate these techniques for their potential applications in computer-assisted drug discovery and design.

Mitochondrial dysfunction is involved in Alzheimer’s disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.

Area covered: Proteomics studies and their contribution to our understanding of mitochondrial dysfunction in AD pathogenesis.

Expert opinion: Proteomics has proven to be an efficient tool to uncover various aspects of this complex organelle, which will broaden our understanding of mitochondrial dysfunction in AD. Evidently, mitochondrial dysfunction is an early biochemical event that might play a central role in driving AD pathogenesis.