Biology subjects

Milea, D.

Publications and source records attributed to Milea, D..

8 recordsLinked to original sources

bioRxiv2025

Morphological and functional alteration of light perception circuits in AD patients

Disruption of sleep and circadian rhythms is one of the earliest symptoms of Alzheimers disease (AD). Circadian entrainment and modulation of alertness are non-visual responses to light driven by intrinsically photosensitive retinal ganglion cells (ipRGCs). To explore structural and functional changes of ipRGCs and ipRGC circuits in AD, we analyzed the retinas and brains of 13 elderly patients ranging from normal cognition to AD and performed ex vivo extracellular electrophysiological recordings on freshly harvested retinas. While rods and cones were moderately impaired, there was a severe loss of ipRGCs in AD donors. Importantly, the remaining ipRGCs exhibited morphological alterations, hyperexcitability, and were not able to sustain high levels of activation. These changes may be ipRGC subtype-specific and correlated with disease progression. Altered ipRGC circuits and function could contribute to the disruption of sleep and circadian rhythms reported in AD patients. Measuring ipRGC-dependent responses to light could be a promising way to predict or monitor pathological changes in the brain.

neuroscience↗

bioRxiv2025

A spiking LIF model captures the role of Somatostatin and Parvalbumin neurons in generating oscillations in V1

PurposeOscillations in the primary visual cortex of the mammalian brain have been demonstrated to arise from the balance between excitatory and inhibitory activity. Experimental studies suggest that different inhibitory neuron populations might make specific contributions to such oscillations, but the underlying mechanism has not yet been assessed. MethodsWe modified a standard excitatory-inhibitory spiking neuron model of layer 4 of the primary visual cortex and we investigated the effects on oscillations of the differentiation of inhibitory neurons in somatostatin and parvalbumin neurons. ResultsOur model reproduced the hypothesis that somatostatin and parvalbumin neurons are responsible for beta (15-25)Hz and gamma (40-70)Hz band oscillations, respectively. ConclusionTo date, this is the simplest model accounting for this phenomenon and could therefore be suited to study pathologies in which the two populations have specific roles, such as migraine.

neuroscience↗

bioRxiv2022

A duration-dependent interaction between high-intensity light and optical refocus in the drive for myopia control

PURPOSETo evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and optical refocus (RF) on lens-induced myopia (LIM) development in chickens. METHODSMyopia was induced in one eye in chicks (10 groups, n=126) from day 1 post- hatching (D1) until D8 using -10D lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to continuous 2 hours (h), 4h, or 6h of either HL (15,000 lux); RF (removal of -10D lens); or both (HL+RF). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as inter-ocular difference (IOD= experimental - control eye) {+/-}SEM. RESULTSBy D8, LIM increased AL (0.36{+/-}0.04 mm), myopic refraction (-9.02{+/-}0.37D), and choroidal thinning (-90.27{+/-}16.44 {micro}m) in the LIM group (all, P<0.001). Compared to the LIM group, exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced myopic refraction in a duration-dependent manner, with RF being more effective than HL (P<0.05). Only 6h of HL+RF (not 2h or 4h) prevented LIM and was more effective than RF (P=0.004) or HL (P<0.001) in reducing myopic refraction, and more effective than HL (P<0.001) in reducing axial elongation. CONCLUSIONDaily exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6h of HL+RF completely stopped LIM development. The synergetic effect of HL and RF is dependent on the duration of the interventions.

neuroscience↗

bioRxiv2021

Adduction Induces Large Optic Nerve Head Deformations in Subjects with Normal Tension Glaucoma

Purpose: To assess optic nerve head (ONH) deformations and strains during adduction, abduction, and intraocular pressure (IOP) elevation in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Design: Clinic-based cross-sectional study. Participants: 114 HTG subjects and 114 NTG subjects. Methods. We recruited 228 subjects (114 subjects with HTG [pre-treatment IOP > 21mmHg] and 114 with NTG [pre-treatment IOP < 21mmHg]). For each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degree adduction, (3) 20 degree abduction, and (4) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the prelaminar tissue (PLT), the choroid, the sclera and the lamina cribrosa (LC) using a deep learning algorithm. We also digitally aligned the OCT volumes obtained from (2)-(4) to the primary gaze volume (1) before performing digital volume correlation (DVC) analysis to quantify IOP- and gaze-induced ONH tissues three-dimensional displacements and effective strain (a local measure of tissue deformation) for all scenarios. Main Outcome Measures: Three-dimensional ONH displacements and strains. Results: Across all subjects, adduction generated high effective strain (4.2 {+/-} 1.4%) in the ONH tissues with no significant difference (p>0.05) with those induced by IOP elevation (4.5 {+/-} 1.5%); while abduction generated significantly lower (p = 0.014) effective strain (3.8 {+/-} 1.1%). Interestingly, the LC of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG:4.6 {+/-} 1.7% vs NTG:4.1 {+/-} 1.5%, p = 0.047). Conversely, the LC tissue of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9 {+/-} 1.9% vs HTG: 4.0 {+/-} 1.4%, p = 0.041). Conclusion: We found that adduction produced comparable strains and displacements as IOP elevation. We also found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects - and that these differences were most pronounced in the LC tissue.

bioengineering↗

bioRxiv2021

Recovery from form-deprivation myopia in chicks is dependent upon the fullness and correlated colour temperature of the light spectrum

BackgroundTo evaluate the impact of full-spectrum light-emitting diodes (LEDs) mimicking sunlight on ocular axial elongation and refractive error development in a chicken model of myopia. MethodsA total of 39 chicks (Lohmann brown), 1 day-old, were randomly distributed into 3 groups. Animals were housed for 28 days in a temperature-controlled enclosure, under a 12/12h light/dark cycle of isoluminant ([~]285 Lux) fluorescent [n = 18, (4000K, FL-4000)] or Sunlike-LED [n=12, (4000K, SL-4000); n = 9, (6500K, SL-6500)] white lights. Myopia was induced monocularly in all chicks by random occlusion of one eye with a frosted diffuser, from day 1 post-hatching (D1) until D14. On D14, diffusers were removed, and recovery from myopia was monitored under the same experimental light condition. Axial length (AL), refractive status, choroidal thickness and anterior chamber depth were recorded on days 1, 7, 14, 22 and 28. Ex vivo scleral collagen fibre thicknesses were measured from scanning electron microscopy images. Differences in outcome measures between eyes and groups were compared using 2-way repeated-measures ANOVA. ResultsThere was no significant difference between groups in the AL and refraction of form-deprived (FD) eyes during form-deprivation (D1 to D14). FD eyes of animals raised under SL-4000 and SL-6500 recovered more rapidly from excessive axial elongation than those of animals raised under FL-4000, by D22 and D28. Correspondingly, the refractive status of FD eyes exposed to SL-4000 and SL-6500 was close to that of control eyes by D28. The choroid became thicker during recovery in FD eyes compared to control eyes, in all groups. Choroidal thickness was significantly greater in FD eyes of chickens raised under SL-6500 than in animals raised under FL-4000 (P < 0.01). The diameter of scleral collagen fibrils was significantly greater in recovering FD eyes of chickens raised under SL-6500, than in those raised under FL-4000 (P = 0.04) and SL-4000 (P = 0.002). ConclusionsCompared to fluorescent light, moderate intensities of full-spectrum Sunlike-LEDs can accelerate recovery from form-deprivation myopia in chickens, potentially through choroid-mediated pathways increasing the diameter of scleral collagen fibrils. This study highlights an important implication of the spectral content of white light on ocular growth and emmetropization.

neuroscience↗

bioRxiv2020

Gaze-evoked deformations of the optic nerve head in thyroid eye disease

PurposeTo assess gaze evoked deformations of the optic nerve head (ONH) in thyroid eye disease (TED), using computational modelling and optical coherence tomography (OCT). MethodsMultiple finite element models were constructed: One model of a healthy eye, and two models mimicking effects of TED; one with proptosis and another with extraocular tissue stiffening. Two additional hypothetical models had extraocular tissue softening or no extraocular tissue at all. Horizontal eye movements were simulated in these models. OCT images of the ONH of 10 healthy volunteers and 1 patient with TED were taken in primary gaze. Additional images were recorded in the same subjects performing eye movements in adduction and abduction. The resulting ONH deformation in the models and human subjects was measured by recording the tilt angle (relative antero-posterior deformation of the Bruchs membrane opening). Effective stress was measured in the peripapillary sclera of the models. ResultsIn our computational models the eyes with proptosis and stiffer extraocular tissue had greater gaze-evoked deformations than the healthy eye model, while the models with softer or no extraocular tissue had lesser deformations, in both adduction and abduction. Scleral stress correlated with the tilt angle measurements. In healthy subjects, the mean tilt angle was 1.46{degrees} {+/-} 0.25 in adduction and -0.42{degrees} {+/-} 0.12 in abduction. The tilt angle measured in the subject with TED was 5.37{degrees} in adduction and -2.21{degrees} in abduction. ConclusionsComputational modelling and experimental observation suggest that TED can cause increased gaze-evoked deformations of the ONH.

bioengineering↗

bioRxiv2019

Nicotinamide Deficiency In Primary Open-Angle Glaucoma

PurposeTo investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG).\n\nMethodsPlasma of 34 POAG individuals were compared to that of 30 age-and sex-matched controls using a semi-quantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls.\n\nResultsUsing the semi-quantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 {micro}M (median: 0.12 {micro}M; range: 0.06-0.28 {micro}M) in the POAG group (-30 %; p = 0.022), and 0.19 {micro}M (median: 0.18 {micro}M; range: 0.08-0.47 {micro}M) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (-33 %; p = 0.011) in the replicative cohort with mean concentrations of 0.14 {micro}M (median: 0.14 {micro}M; range: 0.09-0.25 {micro}M) in the POAG group, and 0.19 {micro}M (median: 0.21 {micro}M; range: 0.09-0.26 {micro}M) in the control group.\n\nConclusionsGlaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.

biochemistry↗

bioRxiv2018

Optic Nerve Tortuosity and Globe Proptosis in Normal and Glaucoma Subjects

PurposeTo assess the difference in optic nerve tortuosity during eye movements and globe proptosis between primary open angle glaucoma and normal subjects using orbital magnetic resonance imaging.\n\nMethods10 Chinese subjects matched for age, ethnicity and refractive errors were recruited, including five normal controls and five patients with primary open angle glaucoma. All subjects underwent magnetic resonance imaging to assess their optic nerves and globes for three eye positions: primary gaze, adduction and abduction. Optic nerve tortuosity (optic nerve length divided by the distance between two ends) and globe proptosis (maximum distance between cornea and interzygomatic line) were measured from magnetic resonance imaging images.\n\nResultsIn adduction, the tortuosity of normal eyes was significantly larger than that of the glaucomatous eyes. Optic nerve tortuosity in adduction in the control and glaucoma groups were 1.004{+/-}0.003 (mean {+/-} standard deviation) and 1.001{+/-}0.001, respectively (p=0.037). Globe proptosis (primary gaze) in glaucoma subjects (19.14{+/-}2.11 mm) was significantly higher than that in control subjects (15.32{+/-}2.79 mm; p = 0.046).\n\nConclusionsIn this sample, subjects with glaucoma exhibited more taut optic nerves and more protruding eye globes compared to normal eyes. This may impact optic nerve head deformations in anatomically predisposed patients.\n\nPrecisEyes with glaucoma have tauter optic nerves compared with normal eyes, which may exert more force on the optic nerve head tissues during eye movements.

pathology↗