Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the ...levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.
Background-It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to ...quantitatively summarize the levels of tear cytokines in DED. Methods-The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results-Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions-Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.
TFOS DEWS II Sex, Gender, and Hormones Report Sullivan, David A.; Rocha, Eduardo M.; Aragona, Pasquale ...
The ocular surface,
July 2017, 2017-Jul, 2017-07-00, 20170701, Letnik:
15, Številka:
3
Journal Article
Recenzirano
One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This ...sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs).
In addition to sex, gender also appears to be a risk factor for DED. “Gender” and “sex” are words that are often used interchangeably, but they have distinct meanings. “Gender” refers to a person’s self-representation as a man or woman, whereas “sex” distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health.
Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED.
Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The ...impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.
Lactoferrin (Lf), a multifunctional protein found abundantly in secretions, including tears, plays a crucial role in ocular health through its antimicrobial, immunoregulatory, anti-inflammatory, and ...antioxidant activities. Advanced delivery systems are desirable to fully leverage its therapeutic potential in treating ocular diseases. The process of Lf quantification for diagnostic purposes underscores the importance of developing reliable, cost-effective detection methods, ranging from conventional techniques to advanced nano-based sensors. Despite the ease and non-invasiveness of topical administration for ocular surface diseases, challenges such as rapid drug elimination necessitate innovations, such as Lf-loaded contact lenses and biodegradable polymeric nanocapsules, to enhance drug stability and bioavailability. Furthermore, overcoming ocular barriers for the treatment of posterior segment disease calls for nano-formulations. The scope of this review is to underline the advancements in nanotechnology-based Lf delivery methods, emphasizing the pivotal role of multidisciplinary approaches and cross-field strategies in improving ocular drug delivery and achieving better therapeutic outcomes for a wide spectrum of eye conditions.
The use of blood‐derived products (Eye Drop of Human Origin—EDHO; in Italian: Emocomponents for Not Transfusional Use, EUNT) for the treatment of various ocular surface diseases has become ...increasingly utilized in ophthalmic practice over the years. In particular, they are recommended as a third line option, when conventional tear substitutes, or active drugs, such as corticosteroids or Cyclosporine A, result unsuccessful in controlling either signs and, perhaps most importantly, subjective symptoms of discomfort and pain. The rationale for their use is based on the stimulation of cell proliferation and migration through the supply of metabolically active substances, in particular growth factors, and definitely mimicking the function of natural tears.
EDHO have been used for the treatment of various ocular surface diseases, including dry eye, persistent corneal epithelial defect, corneal ulcer, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion and limbal stem cell deficiency. However, the therapeutic potential of these products is still to be fully explored, as randomized clinical trials and internationally recognized harmonized guidelines are still needed to provide better evidence, improve quality of the final products and lead to a more widespread use of these therapies in daily clinical practice. The autologous source is still quite popular, although allogeneic sources appear to be a promising innovation. These might offer the solution of obtaining in advance products tailored for each patient and ocular surface disease, at scalable concentrations based on the severity of the disease and clinical parameters. There remain many unanswered questions regarding what might be considered optimal treatment, sketched as “The 5 Ws (and 2 H) for blood based eye drops”, to quote a review from our group (doi: 10.3390/jcm8091478). This presentation will discuss: 1. who is the patient to be treated, in terms of disease type, severity, and stage?; 2. Why is an EDHO needed, in terms of a target indication?; 3. When is it appropriate to prescribe an EDHO therapy?; 4. Where are EDHO be dispensed, and is a national/regional program a feasible solution to optimize resources?; 5. What is the EDHO of choice, which source and preparation are targeted for a given patient? And further: 1. how is EDHO standardized in terms of processing to ensure an optimal dilution, solvent, dispenser, storage time?; 2. How is EDHO delivered to the ocular surface, in terms of form, dose‐size modulation, length of treatment?
An interdisciplinary work with transfusional medicine specialists is imperative to share information and competences, to achieve a better clinical management.
This presentation summarizes the findings of the Nutrition Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease” ...(www.tearfilm.org). It is now recognized that unhealthy nutrition habits, which include either under and over eating, can impair our daily wellbeing and contribute to the risk of developing several diseases. Nutrients are substances required by the body to perform its basic functions, and must be obtained from our diet. They are broadly classified into three groups: macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals), and water. In the report each element of nutrition and its known impact on the ocular surface is discussed on the basis of scientific evidence. Vitamin deficiencies, such as vitamin A and C, have been consistently associated with ocular surface impairment, but links with other systemic nutritional deficiencies are far less established, and just hypothesized at present. The influence of factors such as age, sex, ethnicity, socioeconomical issues on nutrition, and the modulation of the gut microbiome to improve ocular surface disease are also explored. Certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body, thus leading to deficiencies of micro‐ and macro‐nutrients that are important in maintaining ocular surface health.
Among supplements, the omega‐3 and omega‐6 polyunsaturated fatty acids are the most extensively studied dietary supplements in ocular surface disease, with numerous randomized controlled trials, systematic reviews and meta‐analyses, mostly in patients with dry eye disease, and showing low to moderate certainty evidence for a reduction in either symptoms and signs.
An overarching issue identified in the report is the relative paucity of high‐quality evidence in explaining the role of nutrition in ocular surface health and disease. Eye doctors are advised to consider the evidence prior to providing nutritional recommendations to patients with respect to treatment for an ocular surface disease.
Oxidative stress and inflammation determine retinal ganglion cell degeneration, leading to retinal impairment and vision loss. Müller glial cells regulate retinal repair under injury, through ...gliosis. Meanwhile, reactive gliosis can turn in pathological effects, contributing to neurodegeneration. In the present study, we tested whether Cord Blood Serum (CBS), rich of growth factors, might improve the viability of Müller cells under in vitro damage. BDNF, NGF, TGF-α, GDNF and EGF levels were measured in CBS samples by Human Magnetic Luminex Assay. CBS effects were evaluated on rat (rMC-1) and human (MIO-M1) Müller cells, under H2O2 and IL-1β damage. Cells grown with FBS or CBS both at 5% were exposed to stress and analyzed in terms of cell viability, GFAP, IL-6 and TNF-α expression. CBS was also administrated after treatment with K252a, inhibitor of the neurotrophin receptor Trk. Cell viability of rMC-1 and MIO-M1 resulted significantly improved when pretreated with CBS and exposed to H2O2 and IL-1β, in comparison to the standard culture with FBS. Accordingly, the gliosis marker GFAP resulted down-regulated following CBS priming. In parallel, we observed a lower expression of the inflammatory mediators in rMC-1 (TNF-α) and MIO-M1 (IL-6, TNF- α), especially in presence of inflammatory damage. Trk inhibition through K252a administration impaired the effects of CBS under stress conditions on MIO-M1 and rMC-1 viability, not significantly different from FBS condition. CBS is enriched with neurotrophins and its administration to rMC-1 and MIO-M1 attenuates the cytotoxic effects of H2O2 and IL-1β. Moreover, the decrease of the main markers of gliosis and inflammation suggests a promising use of CBS for neuroprotection aims. This study is a preliminary basis that prompts future investigations to deeply explore and confirm the CBS potential.
Inflammation in MGD Versura, Piera
Acta ophthalmologica (Oxford, England),
December 2022, 2022-12-00, 20221201, Letnik:
100, Številka:
S275
Journal Article
Recenzirano
Meibomian gland dysfunction (MGD) is thought to be the leading cause of dry eye disease (DED), a multifactorial disorder in which inflammation plays a significant role in the progression and ...symptoms. Any dysfunction of the meibomian glands modifies the secreted meibum, and such quantitative and/or qualitative changes impair the ocular surface system in several ways, including triggering inflammation. According to the report presented by the DEWS MGD Workshop, the term meibomitis describes MGD associated with diffuse or focal inflammation of the meibomian glands, although inflammation is not always present. Meibomitis is an inflammatory form of MGD, which often coexists with ocular surface inflammation in conditions such as blepharokeratoconjunctivitis, ocular rosacea and flictenular keratitis. Obstructive MGD, the most commonly observed type of MGD, is considered a precursor of meibomitis.
This presentation is focused onto evaluation and staging of inflammatory status in MGD either at the clinical level, in the laboratory setting, and emerging analytical techniques. In particular, the need to standardize the inflammatory panel is stressed, with the aim to stratify subjects by biomarkers with more accurate diagnostic accuracy.
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