scholarly journals Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation

2021 ◽  
pp. 108628
Author(s):  
Nikhil G. Menon ◽  
Ruchi Goyal ◽  
Carolina Lema ◽  
Paige S. Woods ◽  
Adam P. Tanguay ◽  
...  
Keyword(s):  
Dry Eye ◽  
2020 ◽  
Author(s):  
Nikhil G. Menon ◽  
Ruchi Goyal ◽  
Carolina Lema ◽  
Paige S. Woods ◽  
Gregory D. Jay ◽  
...  

AbstractPurposeDry eye disease (DED) affects hundreds of millions worldwide. Proteoglycan 4 (PRG4) has been shown to improve signs and symptoms of DED in humans. The objectives of this study were to characterize endogenous PRG4 expression by telomerase-immortalized human corneal epithelial (hTCEpi) cells, examine how exogenous recombinant human PRG4 (rhPRG4) modulates cytokine and chemokine secretion in response to TNFα and IL-1β, explore rhPRG4 as a potential substrate and/or inhibitor of MMP-9, and to understand how experimental dry (EDE) in mice affects PRG4 expression.MethodsPRG4 secretion was quantified by Western blotting and PRG4 expression by immunocytochemistry. Cytokine/chemokine release was measured by ELISA, and MMP-9 inhibition was quantified using an MMP-9 inhibitor kit. EDE was induced in mice, and PRG4 was visualized by immunohistochemistry in the cornea and Western blotting in lacrimal gland lysate.ResultshTCEpi cells synthesize and secrete PRG4 in vitro, which is inhibited by TNFα and IL-1β. TNFα and IL-1β significantly increased secretion of cytokine IL-6 and chemokines IL-8, IP-10, RANTES, and ENA-78, and several of these chemokines were downregulated after cotreatment with rhPRG4. Fluorescently-labelled rhPRG4 was internalized by hTCEpi cells. rhPRG4 was not digested by MMP-9 and inhibited in vitro activity of exogenous MMP-9 both in solution and in the presence of human tears. Finally, EDE decreased corneal and lacrimal gland expression of PRG4.ConclusionsThese results demonstrate rhPRG4’s anti-inflammatory properties in the corneal epithelium and its contribution to ocular surface homeostasis, furthering our understanding of PRG4’s immunomodulatory properties in the context of DED inflammation.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Asuka Kobayashi ◽  
Takeshi Ide ◽  
Teruki Fukumoto ◽  
Emiko Miki ◽  
Kazuo Tsubota ◽  
...  

Purpose. Meibomian gland dysfunction (MGD) can lead to abnormalities in the composition and function of tear film, resulting in dry eye. Eyelid hygiene is a key to management of MGD. We tested a novel eyelid shampoo (Eye Shampoo Long, ESL) for its ability to maintain lid hygiene. This shampoo is nonirritating and can potentially lengthen eyelashes. This study was aimed to evaluate the efficacy of ESL in the treatment of MGD and its effects on eyelash length. Methods. Ten patients with MGD and 10 healthy subjects without MGD applied ESL twice daily for 8 weeks. Patients were examined for lid margin and dry eye before and after the trial. Subjective symptoms were evaluated. Eyelash length was measured at baseline and at the end of the trial. Results. In the MGD group, significant improvements were observed in subjective symptoms obstruction of the meibomian orifice, secretion of meibum, eyelashes contamination, eyelid margin foam, and SPK. Eyelash length became significantly longer. Conclusions. Maintaining eyelid hygiene using ESL improved the eyelid margins and symptoms of dry eye in MGD patients and increased eyelash length. These findings are promising and warrant confirmation in a larger randomized controlled study.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jiaxin Xiao ◽  
Muhammed Yasin Adil ◽  
Jonatan Olafsson ◽  
Xiangjun Chen ◽  
Øygunn A. Utheim ◽  
...  

AbstractMeibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1–4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p < 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96–1.0) for gland loss, and 0.96 (CI 0.91–1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = −0.53; p < 0.001) and DESL (r = −0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Masatoshi Miyamoto ◽  
Takayuki Sassa ◽  
Megumi Sawai ◽  
Akio Kihara

Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-hydroxy fatty acids (OAHFAs), a subclass of these lipids, are thought to be involved in connecting the lipid and aqueous layers in tears, although their actual function and synthesis pathway have to date remained unclear. Here, we reveal that the fatty acid ω-hydroxylase Cyp4f39 is involved in OAHFA production. Cyp4f39-deficient mice exhibited damaged corneal epithelium and shortening of tear film break-up time, both indicative of dry eye disease. In addition, tears accumulated on the lower eyelid side, indicating increased tear surface tension. In Cyp4f39-deficient mice, the production of wax diesters (type 1ω and 2ω) and cholesteryl OAHFAs was also impaired. These OAHFA derivatives show intermediate polarity among meibum lipids, suggesting that OAHFAs and their derivatives contribute to lipid polarity gradient formation for tear film stabilization.


2020 ◽  
pp. jlr.TR120000874 ◽  
Author(s):  
Douglas Borchman

     Lens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen than any other tissue and contains almost no intracellular organelles. The tear film lipid layer (TFLL) is also unique. The TFLL is a thin, 100 nm layer of lipid on the surface of tears covering the cornea that contributes to tear film stability. The major lipids of the TFLL are wax esters and cholesterol esters that are not found in the lens. The hydrocarbon chains associated with the esters are longer than those found anywhere in the body, as long as 32 carbons, and many are branched. Changes in the composition and structure of the 30,000 different moieties of TFLL contribute to the instability of tears. The focus of the current review is how spectroscopy has been used to elucidate the relationships between lipid composition, conformational order and function and the etiology of cataract and dry eye.


2021 ◽  
Vol 10 (38) ◽  
pp. 3322-3326
Author(s):  
Priyadarshini Palaniyapphan ◽  
Mary Thomas ◽  
Gayatri Sundareswaran ◽  
Sanjana Chilukuri

BACKGROUND Due to the higher prevalence of dry eye disease (DED) in postmenopausal women, it is essential to understand the effects of sex hormones on the ocular surface. This study was done to identify the association between serum concentration of 17 beta estradiol E2 and DED in postmenopausal women. METHODS Our study population comprised of 100 postmenopausal women who were segregated into two groups – 50 symptomatic participants in dry eye group and 50 asymptomatic participants in normal eye group (NEG), based on the dry eye questionnaire assessment. Other preliminary tests to detect DED and meibomian gland dysfunction (MGD) such as tear break up time (TBUT), meibum evaluation, ocular staining score (OSS) and Schirmer’s test were performed. All participants underwent venous sampling for measurement of serum concentration of 17 beta estradiol E2. RESULTS 82 % of participants of DEG belonged to older age group (> 60 years) on comparison with NEG (32 %). A shorter TBUT of 5.78 and 5.96 in DEG as compared to 13.44 and 13.08 in NEG were documented in right and left eyes respectively. Mean serum estradiol was significantly higher in DEG (30.90 pg/ml) than in NEG (16.02 pg/ml). With an increase in the severity of MGD stage, an analogous increase in serum estradiol was noted, which was statistically significant (P < 0.001). CONCLUSIONS Higher levels of serum estradiol correspond with higher stages of MGD, suggesting that sex hormone induced alteration of meibomian gland morphology and function plays an important role in postmenopausal DED. KEY WORDS Dry Eye Disease, Meibomian Gland Dysfunction, 17 Beta Estradiol E2, Postmenopausal Women


Author(s):  
Yun Qi ◽  
Yong Wan ◽  
Tianhui Li ◽  
Ming Zhang ◽  
Yu Song ◽  
...  

PurposeThe pathogenesis of dry eye concomitant with autoimmune disease is different from that of dry eye without autoimmune disease. The aim of this study was to explore differences in the microbiota diversity and composition in dry eye with and without autoimmune disease.MethodsSwab samples from the inferior fornix of the conjunctival sac were obtained from dry eye patients without autoimmune disease (n = 49, dry eye group) and from those with autoimmune disease (n = 38, immdry eye group). Isolated bacterial DNAs from swabs were analyzed with 16S rRNA amplicon sequencing.ResultsAnalysis of the alpha diversity revealed no significant differences between subjects in the dry eye and immdry eye groups. Those in the immdry eye group had a distinct microbial composition compared with those in the dry eye group. The combination of the genera Corynebacterium and Pelomonas distinguished subjects in the immdry eye group from those in the dry eye group, with an area under the curve of 0.73 (95% CI = 0.62–0.84). For the same bacteria, the correlations between microbe abundance and the ocular surface parameters were different in the two groups. In addition, the functions of the microbial communities were altered in the two groups.ConclusionsOur study demonstrates changes in the composition and function of the ocular microbiome between subjects in the immdry eye and dry eye groups, which suggests that the potential pathogenesis is different.


2016 ◽  
Vol 78 (2) ◽  
pp. 6 ◽  
Author(s):  
Caitlin J Morrison ◽  
Joseph M Stamm

Purpose: This case report describes the potential impact of tattooed eyeliner on eyelid structure and function resulting in an increase in dry eye symptoms and findings. Case Report: A 59-year-old Hispanic female presented for an evaluation following longstanding dry eye symptoms with little relief from artificial tears. Imaging showed meibomian gland dropout, possibly a result of her tattooed eyeliner. Symptoms and objective measurements improved successfully with warm compresses, lid massage, and lipid-based artificial tears. Conclusions. Permanent tattooed eyeliner may enhance dryness of the eyes in two main ways: disruption of the architecture of the lids and chronic inflammation from tattoo pigment granules. Recognizing these possible effects in patients with tattooed eyeliner may help tailor treatment to be specific to the etiology of the patient’s dry eye: aiding the remaining meibomian glands by utilizing warm compresses, lid massage and supplementing the lipid from the missing meibomian glands by employing lipid-based artificial tears.


2013 ◽  
Vol 91 ◽  
pp. 0-0
Author(s):  
A LABBE ◽  
Q LIANG ◽  
L XU ◽  
C BAUDOUIN ◽  
X SUN

2020 ◽  
Vol 7 ◽  
Author(s):  
Austyn Matheson ◽  
Suresh C. Regmi ◽  
Gregory D. Jay ◽  
Tannin A. Schmidt ◽  
W. Michael Scott

Objective: Local biological and biomechanical-stimuli modulate proteoglycan-4 secretion within synovial joints. For the horse, changes to proteoglycan-4 concentration and function are notable in acute joint injury and osteoarthritis. Proteoglycan-4 (also known as Lubricin) is present in the blood, however the effect of exercise on equine serum levels is unknown. The overall objective of this study was, therefore, to investigate the effect of intense exercise on serum proteoglycan-4 in thoroughbred horses.Methods: Samples of blood were taken from thoroughbreds (n = 12) during a chuckwagon racing event (Alberta, Canada). The chuckwagon race is a sprint racing event where teams of horses pull a combined 1,325 lbs (601 kg) of wagon and driver around a 5/8th mile (1 km) of dirt track, racing at full gallop to the finish. Blood samples were collected 30-min before the race start, and several timepoints post-race: 5-min, 90-min, 3-h, 12-h, and 23-h. Proteoglycan-4 concentrations in serum were quantified by enzyme-linked-immunosorbent-assay using recombinant-human proteoglycan-4 standards and anti-proteoglycan-4 mAb 9G3. The molecular weight of immunoreactive proteoglycan-4 in serum was assessed by western blot.Results: Proteoglyan-4 in serum demonstrated the expected high MW immunoreactivity to mAb 9G3, consistent with that of full length PRG4. Serum proteoglycan-4 decreased five-minutes post-race from baseline concentration (0.815 ± 0.175 to 0.466 ± 0.090 μg/mL, μ ± SEM, p &lt; 0.01).Conclusions: The concentration of serum proteoglycan-4 in horses decreased significantly five min post-exercise. A potential explanation for this finding could be increased proteoglycan-4 clearance from the circulation. Further investigations could extend to complete the detailed characterization of proteoglycan-4 structure and its potential function within the blood as it relates to joint health and exercise.


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