Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson’s disease’s (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female, n = 15–29 per group). In vivo retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) were recorded, and retinal immunohistochemistry and western blot assays were performed to examine retinal α-SYN and tyrosine hydroxylase. Compared to WT controls, A53T mice exhibited reduced light-adapted (cone photoreceptor and bipolar cell amplitude, p < 0.0001) ERG responses and outer retinal thinning (outer plexiform layer, outer nuclear layer, p < 0.0001) which correlated with elevated levels of α-SYN. These retinal signatures provide a high throughput means to study α-SYN induced neurodegeneration and may be useful in vivo endpoints for PD drug discovery.

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson’s disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7–13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning (p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7–13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.

Background Prison-based hepatitis C treatment is safe and effective, however many individuals are released untreated due to time or resource constraints. On community re-entry individuals face a number of immediate competing priorities, and in this context, linkage to hepatitis C care is low. Interventions targeted at improving healthcare continuity following prison release have yielded positive outcomes for other health diagnoses, however data regarding hepatitis C transitional care are limited. Methods We conducted a prospective randomised controlled trial comparing a hepatitis C care navigator intervention with standard of care for individuals released from prison with untreated hepatitis C infection. The primary outcome was prescription of hepatitis C direct-acting antivirals (DAA) within six months of release. Results Forty-six participants were randomised. The median age was 36 years and 59% were male. Ninety percent (n = 36/40) had injected drugs within six months prior to incarceration. Twenty-two were randomised to care navigation and 24 to standard of care. Individuals randomised to the intervention were more likely to commence hepatitis C DAAs within six months of release (73%, n = 16/22 vs 33% n = 8/24, p &lt; 0·01), and the median time between re-entry and DAA prescription was significantly shorter (21 days [IQR 11-42] vs 82 days [IQR 44-99], p = 0·049). Conclusions Care navigation increased hepatitis C treatment uptake amongst untreated individuals released from prison. Public policy should support similar models of care to promote treatment in this high-risk population. Such an approach will help achieve hepatitis C elimination as a public health threat.