Design and Characterization of Model Systems that Promote and Disrupt Transparency of Vertebrate Crystallins In Vitro DOI Creative Commons

Michael R. Bergman,

Sophia A. Hernandez,

Caitlin Deffler

и другие.

Advanced Science, Год журнала: 2023, Номер 10(35)

Опубликована: Окт. 28, 2023

Positioned within the eye, lens supports vision by transmitting and focusing light onto retina. As an adaptive glassy material, is constituted primarily densely-packed, polydisperse crystallin proteins that organize to resist aggregation crystallization at high volume fractions, yet details of how crystallins coordinate with one another template maintain this transparent microstructure remain unclear. The role individual subtypes (α, β, γ) paired subtype compositions, including they experience crowding-induced turbidity in solution, explored using combinations spectrophotometry, hard-sphere simulations, surface pressure measurements. After assaying combinations, β-crystallins emerged as a principal component all mixtures enabled dense fluid-like packing short-range order necessary for transparency. These findings helped inform design lens-like hydrogel systems, which are used monitor manipulate loss transparency under different crowding conditions. When taken together, illustrate characterization materials made from can be better understand mechanisms regulating

Язык: Английский

Aging of the eye: Lessons from cataracts and age-related macular degeneration DOI Creative Commons
Aleš Cvekl, Jan Vijg

Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102407 - 102407

Опубликована: Июль 6, 2024

Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand effects of aging process on these genetic, molecular, and cellular mechanisms that underlie increased disease over lifetime. Understanding increases general knowledge physiology impacted by processes at various biological extremes. Two major age-related cataract macular degeneration (AMD) are caused dysfunction lens retina, respectively. Lens transparency light refraction mediated fiber cells lacking nuclei other organelles, which provides a unique opportunity study single hallmark, i.e., loss proteostasis, within an environment limited metabolism. In AMD, local photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in macula leads photoreceptors eventually central vision, driven nearly all hallmarks shares features with Alzheimer's disease, Parkinson's cardiovascular diabetes. The can function as model studying basic and, vice versa, well-defined be used tools disease.

Язык: Английский

Процитировано

16
BCLA CLEAR presbyopia: Mechanism and optics DOI

Leon N. Davies,

Sayantan Biswas,

Mark Bullimore

и другие.

Contact Lens and Anterior Eye, Год журнала: 2024, Номер 47(4), С. 102185 - 102185

Опубликована: Май 24, 2024

Язык: Английский

Процитировано

10
Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions DOI
Nobuyuki Hamada

Radiation Research, Год журнала: 2023, Номер 200(2)

Опубликована: Июль 6, 2023

For radiation protection purposes, noncancer effects with a threshold-type dose-response relationship have been classified as tissue reactions (formerly called nonstochastic or deterministic effects), and equivalent dose limits aim to prevent occurrence of such reactions. Accumulating evidence demonstrates increased risks for several late occurring at doses rates much lower than previously considered. In 2011, the International Commission on Radiological Protection (ICRP) issued statement recommend threshold 0.5 Gy lens eye cataracts heart brain diseases circulatory system (DCS), independent rate. Literature published thereafter continues provide updated knowledge. Increased below reported in cohorts (e.g., including those receiving protracted chronic exposures). A is less evident longer follow-up, limited available risk cataract removal surgery. There emerging normal-tension glaucoma diabetic retinopathy, but long-held tenet that represents among most radiosensitive tissues body seems remain unchanged. DCS, various cohorts, existence otherwise unclear. The level uncertain rate, possibility per unit greater rates. Target organs DCS are also unknown, may include heart, large blood vessels kidneys. Identification potential factors sex, age, lifestyle factors, coexposures, comorbidities, genetics epigenetics) modify would be important. Other radar neurological Parkinson's disease, Alzheimer's disease dementia) which elevated has increasingly reported. These tend deviate from definition reactions, necessitating more scientific developments reconsider effect classification management. This paper gives an overview historical made ICRP prior 2011 update relevant since statement.

Язык: Английский

Процитировано

19
Through the Cat-Map Gateway: A Brief History of Cataract Genetics DOI Open Access
Alan Shiels

Genes, Год журнала: 2024, Номер 15(6), С. 785 - 785

Опубликована: Июнь 14, 2024

Clouding of the transparent eye lens, or cataract(s), is a leading cause visual impairment that requires surgical replacement with synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract acquired aging as multifactorial complex trait. Cataract may also be inherited classic Mendelian trait—often an early pediatric onset—with without other ocular and/or systemic features. Since 1990s, over 85 genes and loci have been genetically associated age-related forms cataract. While many these underlying genes—including those for crystallins, connexins, transcription factors—recapitulate signature features development differentiation, increasing cohort unpredicted genes, including involved in cell-signaling, membrane remodeling, autophagy, has emerged—providing new insights regarding homeostasis aging. This review provides brief history gene discovery compiled Cat-Map database highlights potential gene-based therapeutic approaches delay, reverse, even prevent formation help reduce demand surgery.

Язык: Английский

Процитировано

7
Gold Nanoparticles and Induction of Structural Alteration and Enhanced Oxidative Stress in Rat Lens DOI
Samaa Samir Kamar,

Lobna A Elkhateb,

Asmaa Mohammed ShamsEldeen

и другие.

Food and Chemical Toxicology, Год журнала: 2025, Номер unknown, С. 115263 - 115263

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone DOI Creative Commons

Mohammad Al-Ansari,

Taylor Fitzsimons,

Wenbin Wei

и другие.

Cell Stress and Chaperones, Год журнала: 2024, Номер 29(1), С. 51 - 65

Опубликована: Фев. 1, 2024

The tardigrade Ramazzottius varieornatus has remarkable resilience to a range of environmental stresses. In this study, we have characterised two members the small heat shock protein (sHSP) family in R. varieornatus, HSP20-3 and HSP20-6. These are most highly upregulated sHSPs response 24 h at 35

Язык: Английский

Процитировано

6
Cholesterol Content Regulates the Interaction of αA-, αB-, and α-Crystallin with the Model of Human Lens-Lipid Membranes DOI Open Access
Raju Timsina, Preston Hazen, Geraline Trossi‐Torres

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1923 - 1923

Опубликована: Фев. 5, 2024

α-Crystallin (αABc) is a major protein comprised of αA-crystallin (αAc) and αB-crystallin (αBc) that found in the human eye lens works as molecular chaperone by preventing aggregation proteins providing tolerance to stress. However, with age cataract formation, concentration αABc cytoplasm decreases, corresponding increase membrane-bound αABc. This study uses electron paramagnetic resonance (EPR) spin-labeling method investigate role cholesterol (Chol) Chol bilayer domains (CBDs) binding αAc, αBc, Chol/model lens-lipid (Chol/MHLL) membranes. The maximum percentage membrane surface occupied (MMSO) Chol/MHLL membranes at mixing ratio 0 followed trends: MMSO > ≈ (αABc), indicating higher amount αAc binds these compared αBc an membranes, decreases until it completely diminished 1.5. Ka trend: (αAc), but was close zero mobility near headgroup regions decreased binding, antagonized capacity decrease regions. No significant change order observed, concentrations. Our results show bind differently ratios 0.5, decreasing increasing hydrophobicity region, likely forming hydrophobic barrier for passage polar ionic molecules, including antioxidants (glutathione), creating oxidative environment inside lens, leading development cataracts. all 1.5, high CBDs inhibit formation barriers protecting against formation.

Язык: Английский

Процитировано

4
Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation DOI Creative Commons
Zongbo Wei, Caili Hao, Kazi Rafsan Radeen

и другие.

Science Advances, Год журнала: 2024, Номер 10(17)

Опубликована: Апрель 26, 2024

A sharp drop in lenticular glutathione (GSH) plays a pivotal role age-related cataract (ARC) formation. Despite recognizing GSH's importance lens defense for decades, its decline with age remains puzzling. Our recent study revealed an truncation affecting the essential GSH biosynthesis enzyme, γ-glutamylcysteine ligase catalytic subunit (GCLC), at aspartate residue 499. Intriguingly, these truncated GCLC fragments compete full-length forming heterocomplex modifier (GCLM) but exhibit markedly reduced enzymatic activity. Crucially, using aspartate-to-glutamate mutation knock-in (D499E-KI) mouse model that blocks truncation, we observed notable delay ARC formation compared to WT mice: Nearly 50% of D499E-KI mice remained cataract-free versus ~20% their 20 months. findings concerning might be key understanding profound reduction age. By halting can rejuvenate levels and considerably postpone onset.

Язык: Английский

Процитировано

4
The Functional Significance of High Cysteine Content in Eye Lens γ-Crystallins DOI Creative Commons
Eugene Serebryany, Rachel W. Martin, Gemma R. Takahashi

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 594 - 594

Опубликована: Май 17, 2024

Cataract disease is strongly associated with progressively accumulating oxidative damage to the extremely long-lived crystallin proteins of lens. Cysteine oxidation affects folding, interactions, and light-scattering aggregation especially due formation disulfide bridges. Minimizing crucial for lifelong lens transparency, so one might expect ubiquitous superfamilies (α βγ) contain little cysteine. Yet, Cys content γ-crystallins well above average human proteins. We review literature relevant this longstanding puzzle take advantage expanding genomic databases improved machine learning tools protein structure prediction investigate it further. observe remarkably low conservation in βγ-crystallin superfamily; however, γ-crystallin, spatial positioning residues clearly fine-tuned by evolution. propose that requirements long-term transparency high optical power impose competing evolutionary pressures on βγ-crystallins, leading distinct adaptations: but βB-crystallins. Aquatic species need more powerful lenses than terrestrial ones, which explains methionine many fish γ- (and even β-) crystallins. Finally, we discuss synergies between sulfur-containing aromatic crystallins suggest future experimental directions.

Язык: Английский

Процитировано

4
Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon? DOI Creative Commons
Jingyan Li, Francesco Buonfiglio, Ying Zeng

и другие.

Antioxidants, Год журнала: 2024, Номер 13(10), С. 1249 - 1249

Опубликована: Окт. 16, 2024

Cataracts, a leading cause of blindness worldwide, are closely linked to oxidative stress-induced damage lens epithelial cells (LECs). Key factors contributing cataract formation include aging, arterial hypertension, and diabetes mellitus. Given the high global prevalence cataracts, burden cataract-related visual impairment is substantial, highlighting need for pharmacological strategies supplement surgical interventions. Understanding molecular pathways involved in stress during development may offer valuable insights designing novel therapeutic approaches. This review explores role formation, focusing on critical mechanisms, such as mitochondrial dysfunction, endoplasmic reticulum stress, loss gap junctions, various cell death LECs. Additionally, we discuss emerging potential targeting options, including antioxidant-based treatments.

Язык: Английский

Процитировано

4