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(A) Bright-field image of a ferning dentrite and relative Raman images obtained selecting the lipids band area (B) 2800-2900 cm −1 , (C) the proteins band 2900-3000 cm −1 and (D) water band from 3100 to 3700 cm −1 . The scale bar is 1 µm.
Source publication
Tear fluid is a heterogeneous solution containing mainly proteins, lipids, mucins and electrolytes, which regulates the physiology of the human eye. The complex composition of tears can be altered in the presence of eye inflammations. The use of contact lenses is one of the most frequent causes of inflammatory responses of the eye, with the related...
Contexts in source publication
Context 1
... Figure 3, we show the bright-field image of a ferning dentrite (part A) and the Raman scan images created by mapping three significant spectral regions: the 2800-2900 cm −1 region, which is mainly caused by CH 2 bonds in lipids; the 2900-3000 cm −1 region, mainly caused by CH 3 bonds in proteins; and the 3100-3700 cm −1 region, related to OH stretch (part B, C and D, respectively). ...
Context 2
... Figure 3C,D reproduce the border of the fern, revealing a major proteins and water soluble components contribution at the peripheral area compared to the lipids one, which is instead concentrated in the inner part ( Figure 3B). Spatial segregation of the different biochemical components in the tear drop is a crucial issue in order to gain information on the proteins/lipids components of the tear fluid. ...
Context 3
... Figure 3C,D reproduce the border of the fern, revealing a major proteins and water soluble components contribution at the peripheral area compared to the lipids one, which is instead concentrated in the inner part ( Figure 3B). Spatial segregation of the different biochemical components in the tear drop is a crucial issue in order to gain information on the proteins/lipids components of the tear fluid. ...
Similar publications
Water Gradient Contact Lens (WGCL) is a new generation material that combines the benefits of Silicone hydrogel (SiHy) and traditional hydrogel contact lenses by modifying the materials between the core and the surface. However, its impact on tear proteome has not been explored. Tears were collected on healthy young adults using Schirmer's strip at...
Citations
... The use of contact lenses (CLs) often causes inflammatory responses in the eye since it alters the natural arrangement and functions of tear film. To reveal the interaction between CL and tear, biochemical changes in the tears of the same individual before and after wearing hydrogel and silicon hydrogel CLs were studied using DCDRS (Capaccio et al., 2019). The experimental results show an alteration of the relative concentrations of proteins and lipids in both of the analyzed cases, indicating the ability of RS to evaluate the changes in tears induced by CLs. ...
Ophthalmic and many systemic diseases may damage the eyes, resulting in changes in the composition and content of biomolecules in ocular biofluids such as aqueous humor and tear. Therefore, the biomolecules in biofluids are potential biomarkers to reveal pathological processes and diagnose diseases. Raman spectroscopy is a non-invasive, label-free, and cost-effective technique to provide chemical bond information of biomolecules and shows great potential in the detection of ocular biofluids. This review demonstrates the applications of Raman spectroscopy technology in detecting biochemical components in aqueous humor and tear, then summarizes the current problems encountered for clinical applications of Raman spectroscopy and looks forward to possible approaches to overcome technical bottlenecks. This work may provide a reference for wider applications of Raman spectroscopy in biofluid detection and inspire new ideas for the diagnosis of diseases using ocular biofluids.
... The complex composition of tears can be altered due to eye inflammations. 6 Research has indicated that proinflammatory factors such as interleukin (IL)-1β, IL-17, and IL-8, NOD-like receptor protein 3 (NLRP3) inflammasome, tumor necrosis factor-alpha (TNF-α), and antiinflammatory factors such as IL-10, IL-37 have all been implicated monosodium urate (MSU)-induced gout inflammatory process. 7 However, cytokines in the tears of hyperuricemia and gout patients remained unknown. ...
Objectives:
To explore pro-inflammatory cytokines status in the tear fluid of patients with hyperuricemia and gout and its association with uric acid level.
Methods:
A total of 58 control subjects, 58 hyperuricemia patients including 40 asymptomatic hyperuricemia and 18 gout participants were recruited in this study. For tear analysis, each patient's tears were collected using capillary action microcaps after stimulation. Tear uric acid levels were measured using chemiluminescence. Tear and serum interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay. The correlation of serum and tear uric acid levels with IL-1β and TNF-α were determined.
Results:
Tear uric acid levels were significantly higher in hyperuricemia group (98.2 ± 51.5 vs. 42.7 ± 24.0 µmol/L, p < .001) than in controls group. IL-1β concentrations were significantly higher in hyperuricemia eyes compared to control eyes (210.2 ± 113.9 vs. 142.6 ± 29.8 pg/mL, p < .001). Multiple linear regression analysis showed that tear uric acid levels were independently positively associated with tear IL-1β concentrations (B = 0.192, p < .001). However, no significant correlations were found between serum or tear uric acid and TNF-α level. Moreover, there were no statistically differences of tear IL-1β and TNF-α levels between the asymptomatic hyperuricemia and gout groups.
Conclusions:
Tear uric acid levels were higher in patients with hyperuricemia and gout than in controls. There was a significant positive correlation between tear uric acid value and tear IL-1β level, implying an interaction between hyperuricemia and ocular inflammation responses.
... This includes a study on blood plasma and synovial fluids using DCDRS [194], where the chemical compositions of different deposits were investigated and related to the final dried patterns. Recently, the biochemical changes in the tear fluid of a contact lens wearer have been analyzed by this DCDRS technique, which exhibits an alteration of the relative concentrations of proteins and lipids [195]. In this context, Cameron et al. published a review article in 2017 describing how these two combined techniques could impact clinical science [196]. ...
Drying of biologically-relevant sessile droplets, including passive systems such as DNA, proteins, plasma, and blood, as well as active microbial systems comprising bacterial and algal dispersions, has garnered considerable attention over the last decades. Distinct morphological patterns emerge when bio-colloids undergo evaporative drying, with significant potential in a wide range of biomedical applications, spanning bio-sensing, medical diagnostics, drug delivery, and antimicrobial resistance. Consequently, the prospects of novel and thrifty bio-medical toolkits based on drying bio-colloids have driven tremendous progress in the science of morphological patterns and advanced quantitative image-based analysis. This review presents a comprehensive overview of bio-colloidal droplets drying on solid substrates, focusing on the experimental progress during the last ten years. We provide a summary of the physical and material properties of relevant bio-colloids and link their native composition (constituent particles, solvent, and concentrations) to the patterns emerging due to drying. We specifically examined the drying patterns generated by passive bio-colloids (e.g., DNA, globular, fibrous, composite proteins, plasma, serum, blood, urine, tears, and saliva). This article highlights how the emerging morphological patterns are influenced by the nature of the biological entities and the solvent, micro- and global environmental conditions (temperature and relative humidity), and substrate attributes like wettability. Crucially, correlations between emergent patterns and the initial droplet compositions enable the detection of potential clinical abnormalities when compared with the patterns of drying droplets of healthy control samples, offering a blueprint for the diagnosis of the type and stage of a specific disease (or disorder). Recent experimental investigations of pattern formation in the bio-mimetic and salivary drying droplets in the context of COVID-19 are also presented. We further summarized the role of biologically active agents in the drying process, including bacteria, algae, spermatozoa, and nematodes, and discussed the coupling between self-propulsion and hydrodynamics during the drying process. We wrap up the review by highlighting the role of cross-scale in situ experimental techniques for quantifying sub-micron to micro-scale features and the critical role of cross-disciplinary approaches (e.g., experimental and image processing techniques with machine learning algorithms) to quantify and predict the drying-induced features. We conclude the review with a perspective on the next generation of research and applications based on drying droplets, ultimately enabling innovative solutions and quantitative tools to investigate this exciting interface of physics, biology, data sciences, and machine learning.
... This includes a study on blood plasma and synovial fluids using DCDRS [192], where the chemical compositions of different deposits were investigated and related to the final dried patterns. Recently, the biochemical changes in the tear fluid of a contact lens wearer have been analyzed by this DCDRS technique, which exhibits an alteration of the relative concentrations of proteins and lipids [193]. In this context, Cameron et al. published a review article in 2017 describing how these two combined techniques could impact clinical science [194]. ...
Drying of biologically-relevant sessile droplets, including passive systems (like DNA and proteins), as well as active microbial systems comprising bacteria and algae, have garnered considerable attention over the last decades. Distinct morphological patterns emerge when bio-colloids undergo drying, with significant potential in a range of biomedical applications, spanning bio-sensing, medical diagnostics, drug delivery, and antimicrobial resistance. This review presents a comprehensive overview of bio-colloidal droplets drying on solid substrates, focusing on the experimental progress during the last ten years. We provide a summary of the relevant properties of bio-colloids and link their composition (constituent particles, solvent, and concentrations) to the patterns emerging due to drying. We examined the drying patterns generated by passive bio-colloids (DNA, globular, fibrous, and composite proteins, plasma, serum, blood, urine, tears, saliva). This article highlights how morphological patterns are influenced by the nature of the biological entities and the solvent, micro- and global environmental conditions. Correlations between emergent patterns and the initial droplet compositions enable the detection of potential clinical abnormalities when compared with the patterns of drying droplets of healthy control samples, offering a diagnostic blueprint. Recent experimental investigations of pattern formation in the bio-mimetic and salivary drying droplets, relevant to COVID-19 are also presented. Finally, we summarize the role of biologically active agents in drying process, including bacteria and algae during the drying process. The review concludes with a perspective on the next generation of research and applications based on drying droplets, enabling potential innovations and tools to study this exciting interface of physics, biology, data sciences, and machine learning.
... Both methods provide alternatives to commonplace ELISA approaches that can be deployed rapidly, portably and with small sample sizes, ideal parameters for POC settings. SERS has also been utilised for ex-vivo studies in detecting and monitoring TBI biomarkers in various biofluids 371,372 . 5. Raman Spectroscopy and the Eye 5.1 Ex-Vivo RS analysis of tears and tear meibum have shown promise, studying composition [373][374][375][376][377][378] , eye-related disease 376,[379][380][381] , non-eye-related disease 382,383 and contact lens use 384 . RS of tears has also been used for assessments of AD and mild cognitive impairment using principal component analysis (PCA), to detect change in healthy and disease states 374 . ...
The study of ocular manifestations of neurodegenerative disorders, Oculomics, is a growing field of investigation for early diagnostics, enabling structural and chemical biomarkers to be monitored overtime to predict prognosis. Traumatic brain injury (TBI) triggers cascade of events harmful to the brain, which can lead to neurodegeneration. TBI, termed the silent epidemic is becoming a leading cause of death and disability worldwide. There is currently no effective diagnostic tool for TBI, and yet, early-intervention is known to considerably shorten hospital stays, improve outcomes, fasten neurological recovery and lower mortality rates, highlighting the unmet need for techniques capable of rapid and accurate point-of-care diagnostics, implemented in the earliest stages. This review focuses on the latest advances in the main neuropathophysiological responses and the achievements and shortfalls of TBI diagnostic methods. Validated and emerging TBI-indicative biomarkers are outlined and linked to ocular neuro-disorders. Methods detecting structural and chemical ocular responses to TBI are categorised along with prospective chemical and physical sensing techniques. Particular attention is drawn to the potential of Raman spectroscopy as a non-invasive sensing of neurological molecular signatures in the ocular projections of the brain, laying the platform for the first tangible path towards alternative point-of-care diagnostic technologies for TBI.
... Tear analysis by spectroscopic, HPLC and MS methods are already getting considerable attention for the detection of ophthalmological diseases (such as dry eye, glaucoma, blepharitis, keratitis, conjunctivitis), measuring drug contents in ophthalmic preparations, monitoring effects of contact lens use and investigation of other ophthalmic problems [145,146]. In addition to this, because of the possibility of other disease markers which can be detected in tear fluid, tear studies have received more attention recently in other clinical conditions also (diabetes, cancer, AD, etc.) To generate a protein biomarker profile with tear fluid, Lebrecht and coworkers screened 50 breast cancer subjects and 50 age-matched controls [147]. ...
Introduction: Human blood and saliva are increasingly under investigation for the detection of biomarkers for early diagnosis of non-communicable (e.g.cancers) and communicable diseases like COVID-19. Exploring the potential application of human tears, an easily accessible body fluid, for the diagnosis of various diseases is the need of the hour.Areas covered: This review deals with a comprehensive account of applications of tear analysis using different techniques, their comparison and overall progress achieved till now. The techniques used for tear fluid analysis are HPLC/UPLC/SDS-PAGE, CE, etc., together with ELISA, Mass Spectrometry, etc. But, with advances in instrumentation and data processing methods, it has become easy to couple the various separation methods with highly sensitive optical techniques for the analysis of body fluids.Expert opinion: Tear analysis can provide valuable information about the health condition of the eyes since it contains several molecular constituents, and their relative concentrations may alter under abnormal conditions. Tear analysis has the advantage that it is totally non-invasive. This study recommends tear fluid as a reliable clinical sample to be probed by highly sensitive optical techniques to diagnose different health conditions, with special emphasis on eye diseases.
... The ratio of lipids to proteins in the tears of a volunteer wearing either a HEMA-based soft lens (etafilcon A) or a SiHy contact lens (genifilcon A) reduced transiently (1-10 days) with both lens types but recovered to levels seen without contact lenses after approximately 20 days of wear [411]. Lotrafilcon B SiHy wearers had a significantly lower concentration of cholesterol but higher concentrations of phosphatidylcholine and sphingomyelin in their tears than non-contact lens wearers [412]. ...
Contact lens materials have undergone significant changes over the past 20 years, particularly with respect to the introduction of silicone hydrogel materials. Whilst this development addressed hypoxic issues, other important areas relating to contact lens success, notably comfort, require further research.
Contact lens wettability remains a crucially important part of biocompatibility. Contact lenses can be made more wettable by incorporation of surfactants into blister packs, internal wetting agents, surface treatments or care solutions. However, there remains no clear association between contact lens wettability and comfort, making it challenging to determine the potential for these approaches to be of significant clinical benefit. Most contact lenses are used on a daily wear, reusable basis, which requires them to be disinfected when not worn. The ideal disinfecting solution would also improve comfort during wear. However, balancing these requirements with other factors, including biocompatibility, remains a challenge. Soft lens materials invariably take up and subsequently release certain components of disinfecting solutions onto the ocular surface. This may affect tear film stability and the normal ocular microbiome, and further research is needed in this area to determine whether this has any affect on comfort. Finally, contact lens materials sorb components of the tear film, and these interactions are complex and may change the biochemistry of the tear film, which in turn may affect their comfort.
In conclusion, the interaction between lens materials, tear film and disinfection solution plays an important role in the biocompatibility of lenses. However, the exact role and whether this can be altered to improve biocompatibility and comfort during wear remains debatable. This report summarises the best available evidence to examine this complex relationship and the opportunities for practitioners to enhance in-eye comfort of contemporary lenses, along with providing suggestions for areas of study that may provide further information on this topic.
... Raman spectroscopy has been used to identify AD biomarkers in blood serum 8,18,19 and saliva, 20 and to investigate basic aggregation mechanisms of amyloids. 21 Raman spectroscopy [22][23][24][25] and surface-enhanced Raman spectroscopy (SERS) 26 have also been used to investigate human tears mainly to diagnose eye diseases. In addition to the direct detection of biomarkers, Raman and SERS can evaluate the global changes that the pathological state induces in the tear composition. ...
Significance:
A noninvasive method based on surface-enhanced Raman spectroscopy (SERS) of tears was proposed as a support for diagnosing neurodegenerative pathologies, including different forms of dementia and Alzheimer's disease (AD). In this field, timely and reliable discrimination and diagnosis are critical aspects for choosing a valid medical therapy, and new methods are highly required.
Aim:
The aim is to evince spectral differences in SERS response of human tears from AD affected, mild cognitive impaired (MCI), and healthy control (Ctr) subjects.
Approach:
Human tears were characterized by SERS coupled with multivariate data analysis. Thirty-one informed subjects (Ctr, MCI, and AD) were considered.
Results:
Average SERS spectra from Ctr, MCI, and AD subjects evidenced differences related to lactoferrin and lysozyme protein components. Quantitative changes were also observed by determining the intensity ratio between selected bands. We also constructed a classification model that discriminated among AD, MCI, and Ctr subjects. The model was built using the scores obtained by performing principal component analysis on specific spectral regions (i-PCA).
Conclusions:
The results are very encouraging with interesting perspectives for medical applications as support of clinical diagnosis and discrimination of AD from other forms of dementia.
Brain disorders, including neurodegenerative diseases (NDs) and traumatic brain injury (TBI), present significant challenges in early diagnosis and intervention.
