Search bioRxiv⌕ Search

Biology subjects

Feigl, B.

Publications and source records attributed to Feigl, B..

2 recordsLinked to original sources

The gut microbiome in early age-related macular degeneration

The gut microbiome is implicated in the development of advanced age-related macular degeneration (AMD) but no study has investigated microbial composition in early AMD nor controlled for important microbiome modulators such as diet and light. This is crucial as diet can change the microbiome rapidly as well as affects disease progression. In addition, the light signalling photoreceptors are dysfunctional in AMD. Here we determined the gut microbiota by conducting 16S DNA metagenomic sequencing of 40 faecal samples from 20 participants with and without early AMD. We normalised both groups to the same diet over 5 days and determined gut microbial composition before and after the diet. To control for light, we assessed habitual light exposure with actigraphy and the post-illumination pupil light response (PIPR) quantified photoreceptor signalling. Clostridium termitidis, Bacteroides gallinarum, and Bacteroides finegoldii were significantly abundant in early AMD compared to controls at both time points. Interestingly, pro-inflammatory species such as Sutterella were only significantly abundant in AMD before the diet. After the diet, the gut microbiome shifted to a significantly greater abundance of commensal bacteria in AMD. Controls and AMD patients had a similar ambient light exposure, however the PIPR was significantly reduced in AMD suggesting impaired light signalling. We are the first to show a distinct gut microbiome in early AMD and infer that dietary changes may positively affect the gut microbiome at early stage of the disease.

neuroscience↗

Intrinsically photosensitive retinal ganglion cell mediated pupil function is impaired in Parkinson’s disease

Parkinsons disease is characterised by non-motor symptoms including sleep and circadian disruption, but the underlying aetiology is not well understood. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals from the eye to brain areas controlling circadian rhythms and the pupil light reflex. Here we evaluate the hypothesis that these non-motor symptoms in people with Parkinsons disease may be linked to ipRGC dysfunction. Using chromatic pupillometry, we measured intrinsic (melanopsin-mediated) ipRGC and extrinsic (rod/cone photoreceptor-mediated) inputs to the pupil control pathway in a group of optimally medicated participants with a diagnosis of Parkinsons disease (PD, n = 17) compared to controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. The PD participants underwent additional clinical assessments using the Unified Parkinsons disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (H&Y).\n\nCompared to controls, the PD group demonstrated an attenuated pupil constriction amplitude in response to long wavelength pulsed stimulation, and reduced post-illumination pupil response (PIPR) amplitude in response to both short wavelength pulsed and sinusoidal stimulation. In the PD group, PIPR amplitude did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, UPDRS or H&Y score, or medication dosage. Both groups exhibited similar pupillary unrest in darkness.\n\nWe show that melanopsin and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage Parkinsons disease. Given that the deficits are independent of clinical assessment severity and are observed despite optimal medication, the melanopsin-mediated PIPR may be a biomarker for the detection of Parkinsons disease and its continued monitoring in both medicated and unmedicated individuals.

neuroscience↗