Mitochondrial decline in the ageing old world primate retina: Little evidence for difference between the centre and periphery DOI Creative Commons
Jaimie Hoh Kam,

Harpreet Shinhmar,

Michael B. Powner

et al.

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(5), P. e0273882 - e0273882

Published: May 2, 2023

Mitochondrial decline is a key feature of ageing. The retina has more mitochondria than any other tissue and ages rapidly. To understand human retinal ageing it critical to examine old world primates that have similar visual systems humans, do so across central peripheral regions, as there evidence for early decline. Hence, we mitochondrial metrics in young Macaca fascicularis retinae. In spite reduced ATP with age, primate complex activity did not But membrane potentials were significantly, concomitantly, permeability increased. marker Tom20 declined consistent number, while VDAC, voltage dependent anion channel diffusion pore associated apoptosis increased significantly. these clear age-related changes, was almost no regional differences between the centre periphery metrics. Primate cones die but many showed marked structural vacuous spaces proximal inner segments normally occupied by endoplasmic reticulum (ER), regulate autophagy. cones, ER displaced nucleus transposed outer limiting could become embedded populations. These data are significant changes provide little if aged suffer those periphery.

Language: Английский

Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration DOI Creative Commons
Diogo Trigo,

JoséJoão Vitória,

Odete A. B. da Cruz e Silva

et al.

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(5), P. 991 - 991

Published: Oct. 27, 2022

In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that a variety of functions in ensuring cellular health homeostasis. The plethora functionalities confers them an intrinsic susceptibility internal external stressors (such as mutation accumulation or environmental toxins), particularly so long-lived postmitotic cells such neurons. Thus, it is reasonable postulate involvement mitochondria aging-associated neurological disorders, notably pathologies including Alzheimer's disease Parkinson's disease. On the other hand, biological effects resulting from neurodegeneration can turn affect function, promoting feedback loop further contributing progression neuronal dysfunction death. This review examines state-of-the-art knowledge, focus current research exploring factor neuroregeneration, development therapeutic approaches aimed at restoring homeostasis pathological setting.

Language: Английский

Citations

15

A pupillary contrast response in mice and humans: Neural mechanisms and visual functions DOI
Michael J. Fitzpatrick, Jenna Krizan, Jen-Chun Hsiang

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(14), P. 2404 - 2422.e9

Published: May 1, 2024

Language: Английский

Citations

3

Microlens‐assisted microscopy for biology and medicine DOI

Anna Trukhova,

Marina D. Pavlova, О. В. Синицына

et al.

Journal of Biophotonics, Journal Year: 2022, Volume and Issue: 15(9)

Published: June 12, 2022

Abstract The addition of dielectric transparent microlens in the optical scheme is an effective and at same time simple inexpensive way to increase resolution a light microscope. For these purposes, spherical cylindrical microlenses with diameter 1–100 μm are usually used. focuses into narrow beam called photonic nanojet. An enlarged virtual image formed, which captured by objective In microscopy, successfully applied amplify signals, trapping force tweezers used microsurgery. This review considers design principle microlens‐assisted microscopes. Taking account advantages super‐resolution methods for research life science, examples use biomedical practice discussed detail.

Language: Английский

Citations

13

Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans DOI Creative Commons
Vivek J. Srinivasan, Aaron M. Kho, Pooja Chauhan

et al.

Translational Vision Science & Technology, Journal Year: 2022, Volume and Issue: 11(9), P. 3 - 3

Published: Sept. 2, 2022

Purpose: We employ visible light optical coherence tomography (OCT) to investigate the relationship between myoid, ellipsoid, and band 2 in living human retina. Rather than refute existing theories, we aim reveal new bands better delineate structures at hand. Methods: An upgraded spectral/Fourier domain OCT prototype, with 1.0-µm axial resolution, imaged 13 eyes of young adult subjects (23–40 years old) without a history ocular pathology. The external limiting membrane (band 1) edges were segmented. Reflectivity was examined along inner segment (IS), defined as extending from 1 center, within itself. Results: Images highlight nearly continuously resolved extrafoveal internal membrane, peripheral single-cell thick ganglion cell layer, photoreceptor axonal fiber division into 2a 2b, reflectivity-based IS "m" "e" zones. Discussion: Topography transverse intensity variations outermost 2b suggest an association rods. zone border is consistent myoid–ellipsoid boundary, even recapitulating well-documented distribution mitochondria throughout foveal center. Theories outer retinal reflectivity must adequately explain these observations. Translational Relevance: Findings support that does partially overlap ellipsoid transversally averaged images due length dispersion but argue be 2, suggested by prior quantitative measurements.

Language: Английский

Citations

13

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa DOI Creative Commons
Sang Joon Lee,

Douglas Emery,

Eric Vukmanic

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113054 - 113054

Published: Aug. 31, 2023

Most mutations in retinitis pigmentosa (RP) arise rod photoreceptors, but cone responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of disease. We used mass spectroscopy to follow 13C metabolites delivered outer retina single-cell RNA sequencing assess photoreceptor transcriptomes. The S metabolic transcriptome suggests engagement TCA cycle ongoing response ROS characteristic oxidative phosphorylation, which we link their histone modification transcriptome. Tumor necrosis factor (TNF) its downstream effector RIP3, drive generation via mitochondrial dysfunction, induced activated as cones undergo early apoptosis RP. long/medium-wavelength (L/M) shows enhanced glycolytic capacity, maintains function RP progresses. Then, extracellular glucose eventually diminishes, L/M sustained long-term dormancy by lactate metabolism.

Language: Английский

Citations

7

Using high-resolution microscopy data to generate realistic structures for electromagnetic FDTD simulations from complex biological models DOI
J M Ball, Wei Li

Nature Protocols, Journal Year: 2024, Volume and Issue: 19(5), P. 1348 - 1380

Published: Feb. 8, 2024

Language: Английский

Citations

2

Quantitative imaging and semiotic phenotyping of mitochondrial network morphology in live human cells DOI Creative Commons

Sophie Charrasse,

Victor Racine,

Charlotte Saint-Omer

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(3), P. e0301372 - e0301372

Published: March 28, 2024

The importance of mitochondria in tissue homeostasis, stress responses and human diseases, combined to their ability transition between various structural functional states, makes them excellent organelles for monitoring cell health. There is therefore a need technologies accurately analyze quantify changes mitochondrial organization variety cells cellular contexts. Here we present an innovative computerized method that enables accurate, multiscale, fast cost-effective analysis shape network architecture from confocal fluorescence images by providing more than thirty features. In order facilitate interpretation the quantitative results, introduced two innovations: use Kiviat-graphs (herein named MitoSpider plots) highly multidimensional data visualization mito-cellular configurations form morphospace diagrams (called MitoSigils). We tested our fully automated image tool on rich datasets gathered live normal skin cultured under basal conditions or exposed specific including UVB irradiation pesticide exposure. demonstrated proprietary software (named MitoTouch) sensitively discriminate control stressed dermal fibroblasts, fibroblasts other types (including cancer tissue-derived primary keratinocytes), showing captures subtle differences morphology. Based this novel algorithm, report identification protective natural ingredient mitigates deleterious impact hydrogen peroxide (H2O2) organization. Hence conceived wet-plus-dry pipeline combining cultures, imaging semiotic exhaustive morphology living adherent cells. Our has potential broader applications research areas such as biology medicine, high-throughput drug screening well predictive environmental toxicology.

Language: Английский

Citations

2

VDAC in Retinal Health and Disease DOI Creative Commons
Ying Xu, Shanti R. Tummala,

Xiong-Min Chen

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 654 - 654

Published: June 4, 2024

The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they sent to brain be interpreted images. retina unique in that continuously exposed has highest metabolic rate demand energy amongst all tissues body. Consequently, very susceptible oxidative stress. VDAC, pore outer membrane mitochondria, shuttles metabolites between mitochondria cytosol normally protects cells from damage, but when cell’s integrity greatly compromised initiates cell death. There three isoforms existing evidence indicates expressed retina. However, their precise localization function each type unknown. It appears most retinal express substantial amounts VDAC2 VDAC3, presumably protect them Photoreceptors VDAC2, HK2, PKM2—key proteins Warburg pathway also these cells. Consistent with role initiating death, VDAC overexpressed degenerative diseases retinitis pigmentosa, age related macular degeneration (AMD), glaucoma. Treatment antioxidants or inhibiting oligomerization reduced expression improved survival. Thus, may promising therapeutic candidate treatment diseases.

Language: Английский

Citations

2

Band Visibility in High-Resolution Optical Coherence Tomography Assessed With a Custom Review Tool and Updated, Histology-Derived Nomenclature DOI Creative Commons
Lukas Goerdt, Thomas A. Swain, Deepayan Kar

et al.

Translational Vision Science & Technology, Journal Year: 2024, Volume and Issue: 13(12), P. 19 - 19

Published: Dec. 13, 2024

Purpose: For structure-function research at the transition of aging to age-related macular degeneration, we refined current consensus optical coherence tomography (OCT) nomenclature and evaluated a novel review software for investigational high-resolution OCT imaging (HR-OCT; <3 µm axial resolution). Method: Volume electron microscopy, immunolocalizations, histology, devices informed custom ImageJ-based tool assess retinal band visibility. We examined effects on visibility automated real-time averaging (ART) 9 100 (11 eyes 10 healthy young adults), (10 vs 22 aged), degeneration (AMD; aged, 17 early (e)AMD, 15 intermediate (i)AMD). Intrareader reliability was assessed. Results: Bands not included in are now visible using HR-OCT: inner plexiform layer (IPL) 1-5, outer (OPL) 1-2, segment interdigitation zone 1-2 (OSIZ, including hyporeflective segments), pigment epithelium (RPE) 1-5. Cohen's kappa 0.54–0.88 0.67–0.83 bands subset eyes. IPL-3-5 OPL-2 benefitted from increased ART. OSIZ-2 RPE-1,2,3,5 worse aged than OSIZ-1-2, RPE-1, RPE-5 decreased eAMD iAMD compared Conclusions: reliably identified 28 HR-OCT. Image improved Aging AMD development impacted Translational Significance: Detailed knowledge anatomic structures will enhance precision research, AI training analyses.

Language: Английский

Citations

2

Is our retina really upside down? DOI Creative Commons
Tom Baden, Dan‐Eric Nilsson

Current Biology, Journal Year: 2022, Volume and Issue: 32(7), P. R300 - R303

Published: April 1, 2022

Language: Английский

Citations

10