Influence of lighting on visual performance.

PURPOSE: This review emphasizes the effect of light on visual efficiency, the impact of different lighting focuses, types of lighting, and their influence on vision and productivity. Light sources and standards are intriguing subjects for ophthalmologists. Guidelines regarding the level of lighting influence on visual activities can enhance visual performance.Methods: This article was developed based on literature reviews, with a bibliographic survey conducted in databases such as PubMed, MEDLINE, Web of Science, Embase, LILACS, and SciELO. RESULTS: Provides recommendations for understanding information regarding the influence of lighting on visual performance. CONCLUSION: Proper workplace lighting is crucial for improving visual efficiency, safety, productivity, and worker health. Efficient workplace lighting should avoid light sources directed towards the worker's face, prevent harmful glare, be more intense in the work area, and uniform in the rest of the room. Ophthalmologists should be knowledgeable about and provide guidance on correct lighting to ensure patient comfort and satisfaction with visual correction.

LAMP3 induces ectopic TLR7 expression in salivary gland epithelial cells and amplifies type I IFN production in Sjögren's disease.

OBJECTIVE: Lysosome-associated membrane protein 3 (LAMP3) misexpression in salivary gland epithelial cells plays a causal role in the development of salivary gland dysfunction and autoimmunity associated with Sjögren's disease (SjD). This study aimed to clarify how epithelial LAMP3 misexpression is induced in SjD. METHODS: To explore upstream signaling pathways associated with LAMP3 expression, we conducted multiple RNA sequencing analyses of minor salivary glands from patients with SjD, submandibular glands from a mouse model of SjD, and salivary gland epithelial cell lines. A hypothesis generated by the RNA sequencing analyses was further tested by in vitro and in vivo assays with gene manipulation. RESULTS: Transcriptome analysis suggested LAMP3 expression was associated with enhanced type I interferon (IFN) and IFNγ signaling pathways in patients with SjD. In vitro studies showed that type I IFN but not IFNγ stimulation could induce LAMP3 expression in salivary gland epithelial cells. Moreover, we discovered that LAMP3 overexpression could induce ectopic toll-like receptor 7 (TLR7) expression and type I IFN production in salivary gland epithelial cells both in vitro and in vivo. TLR7 knock-out mice did not develop any SjD-related symptoms following LAMP3 induction. CONCLUSION: Epithelial LAMP3 misexpression can be induced through enhanced type I IFN response in salivary glands. In addition, LAMP3 can promote type I IFN production via ectopic TLR7 expression in salivary gland epithelial cells. This positive feed-back loop can contribute to maintaining LAMP3 misexpression and amplifying type I IFN production in salivary glands, which plays an essential role in the pathophysiology of SjD.

TFOS Lifestyle: Impact of lifestyle challenges on the ocular surface.

Many factors in the domains of mental, physical, and social health have been associated with various ocular surface diseases, with most of the focus centered on aspects of dry eye disease (DED). Regarding mental health factors, several cross-sectional studies have noted associations between depression and anxiety, and medications used to treat these disorders, and DED symptoms. Sleep disorders (both involving quality and quantity of sleep) have also been associated with DED symptoms. Under the domain of physical health, several factors have been linked to meibomian gland abnormalities, including obesity and face mask wear. Cross-sectional studies have also linked chronic pain conditions, specifically migraine, chronic pain syndrome and fibromyalgia, to DED, principally focusing on DED symptoms. A systematic review and meta-analysis reviewed available data and concluded that various chronic pain conditions increased the risk of DED (variably defined), with odds ratios ranging from 1.60 to 2.16. However, heterogeneity was noted, highlighting the need for additional studies examining the impact of chronic pain on DED signs and subtype (evaporative versus aqueous deficient). With respect to societal factors, tobacco use has been most closely linked to tear instability, cocaine to decreased corneal sensitivity, and alcohol to tear film disturbances and DED symptoms.

Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease.

Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren's disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, in vitro and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high LAMP3 mRNA expression in minor salivary glands and those with LAMP3 mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high LAMP3 expression compared those with normal LAMP3 expression. Taken together, these findings suggested that by determining salivary gland LAMP3 mRNA level, a patient's response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD.

Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in Sjögren's syndrome.

BMP6 is a central cytokine in the induction of Sjögren's syndrome-associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.

Correlation between the presumed pterygium with dry eye and with systemic and ocular risk factors.

OBJECTIVE: To estimate the epidemiology of the pterygium and its correlation with dry eye symptoms and with the potential systemic and ocular predictors. METHODS: This study is a population-based, cross-sectional study in which random visits were made to the 600 households of 600 participants of age ≥40 years in Ribeirão Preto-SP (n=420) and Cassia dos Coqueiros-SP (n=180) in Brazil. The participants were subjected to a structured interview with a detailed questionnaire to collect information on demography and the potential risk factors. Next, random participants with pterygium (n=63) or not (n=110) were evaluated for the ocular surface changes. RESULTS: The frequency of pterygium in Ribeirão Preto was 21% (15.7% among women and 32.1% among men; p=0.0002). In Cássia dos Coqueiros, the corresponding frequency was 19.4% (17.3% among women and 25.5% among men; p=0.28). The mean age of the affected individuals was higher than that of the unaffected ones (65.6 ± 10.5 years vs. 61.2 ± 12.0 years, p=0.02). A positive correlation was noted between pterygium and any prior radiotherapy and chemotherapy (p<0.0001, for both). A higher score on corneal fluorescein and conjunctival lissamine green staining was asso ciated with pterygium (p=0.0003 and 0.0001, respectively). CONCLUSION: We noted a high frequency of pterygium in two Brazilian adult populations, mainly among the men and elderly. Ocular surface damage and a previous history of radiotherapy and/or chemotherapy were found to be associated with pterygium.

LAMP3 induces apoptosis and autoantigen release in Sjögren's syndrome patients.

Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by dysfunction of secretory epithelia with only palliative therapy. Patients present with a constellation of symptoms, and the diversity of symptomatic presentation has made it difficult to understand the underlying disease mechanisms. In this study, aggregation of unbiased transcriptome profiling data sets of minor salivary gland biopsies from controls and Sjögren's syndrome patients identified increased expression of lysosome-associated membrane protein 3 (LAMP3/CD208/DC-LAMP) in a subset of Sjögren's syndrome cases. Stratification of patients based on their clinical characteristics suggested an association between increased LAMP3 expression and the presence of serum autoantibodies including anti-Ro/SSA, anti-La/SSB, anti-nuclear antibodies. In vitro studies demonstrated that LAMP3 expression induces epithelial cell dysfunction leading to apoptosis. Interestingly, LAMP3 expression resulted in the accumulation and release of intracellular TRIM21 (one component of SSA), La (SSB), and α-fodrin protein, common autoantigens in Sjögren's syndrome, via extracellular vesicles in an apoptosis-independent mechanism. This study defines a clear role for LAMP3 in the initiation of apoptosis and an independent pathway for the extracellular release of known autoantigens leading to the formation of autoantibodies associated with this disease.ClinicalTrials.gov Identifier: NCT00001196, NCT00001390, NCT02327884.

Endocrine disrupting chemicals associated with dry eye syndrome.

BACKGROUND: Dry eye syndrome (DES) is a multifactorial disease that causes changes in the tear film and occurs more frequently in women. Sex hormones (SHs) influence tear production, and SHs imbalance is associated with DES. Endocrine-disrupting chemicals (EDCs) are compounds that can bind to SHs receptors, changing the SHs action in several organs and tissues. METHODS: The levels of 21 EDCs were measured in the urine of DES patients and healthy controls. All individuals were submitted to eye exams for DES and responded to the questionnaire "Ocular Surface Disease Index (OSDI)". DES was considered present when the OSDI score was >20 and one of the DES tests surpassed the established thresholds. RESULTS: Methyl-protocatechuic acid (OHMeP), had higher urine levels in DES individuals than in control individuals (p = 0.0189). On the other hand, triclocarban (TCC) exhibited lower urine levels in DES individuals than in control individuals (p = 0.0081). Statistically significant positive associations were found between Methyl Paraben (MeP), EtP (ethyl paraben) and OHMeP with fluorescein staining test; between TCC and Tear breakup time test and between OHMeP and OSDI score. Significant negative associations were found between EtP and OHMeP and schirmer test; between OHMeP and Tear breakup time test; between TCC and the OSDI score and fluorescein and lissamine staining test.The quadratic discriminant function classified 94.4% of individuals in their groups based on the urine levels of EDCs. CONCLUSION: The following EDCs, MeP, EtP, and OHMeP, were associated with signs and symptoms of DES. TCC had a paradoxical protective effect against DES. These findings suggest that EDCs are associated with DES and the exposure should be included in the investigation of causes and risk factors for DES.

Prospective insulin-based ophthalmic delivery systems for the treatment of dry eye syndrome and corneal injuries.

The presence of insulin (INS) receptors on the ocular surface (OS) and lacrimal gland (LG), and the high prevalence of dry eye syndrome (DES) and corneal lesions in diabetic patients suggest that INS is relevant for OS homeostasis and wound healing. The study aims at developing delivery systems for the topical administration of INS to the OS in order to improve INS local bioavailability and evaluate the influence of the delivery systems on DES in diabetic rats (DM) (n = 05/group). Chitosan microparticles (MP), chitosan/poloxamer gel (GEL) and MP-loaded GEL (GELMP), with or without INS were developed. Formulations were instilled into the eyes of diabetic rats (DM) for 15 days and the tear fluid volume, corneal cells morphology and cornea thickness were assessed and compared with an aqueous dispersion of INS (DISP-INS). All delivery systems had pH of about 6, osmolality suitable for topical application and positive zeta potential. The MPs with or without INS had sizes close to 4 µm, spherical morphology and INS encapsulation efficiency of 77 ±â€¯6%. DISP-INS and GELMP-INS formulations produced tear secretion amounts significantly higher than those receiving formulations containing no INS and similar to healthy animals. Cornea surface impression cytology showed that treatment with INS-delivery systems and not DISP-INS almost normalized cells morphology. Treatment with GELMP-INS increased INS by 2.5 in the LG and eyeball as compared to the groups treated with GEL-INS and MP-INS, while treatment with DISP-INS left no traces of drug in the eye after treatment termination. GEL and GELMP containing INS were also able to normalize the thickness of the corneal epithelia. In conclusion, GELMP-INS normalized tear fluid volume, corneal thickness, protected corneal cells morphology and increased ocular bioavailability of INS, making it a promising treatment strategy for DES and corneal lesions.

The role of endocrine disruptors in ocular surface diseases.

Endocrine disruptors are a group of compounds that occur in increasing amounts in the environment. These compounds change the hormone homeostasis of the target organs regulated by those hormones, mostly by binding to their receptors and affecting their signaling pathways. Among the hormones altered by endocrine disruptors are sex hormones, thyroid hormones, and insulin. Studies have documented abnormalities in the reproductive and metabolic systems of various animal species exposed to endocrine disruptors. Endocrine disruptors can play a significant role in ocular diseases once hormone deficiency or excess are involved in the mechanism of that disease. Cataracts, dry eye disease and retinal diseases, such as macular hole and diabetic retinopathy, are some of the frequent problems where hormones have been implicated. We found that some compounds function as endocrine disruptors in the metabolism of body organs and systems. The increasing frequency of dry eye and other ocular diseases indicates the need to better investigate the potential relationships beyond the isolated associations mentioned by patients and documented as rare case reports. The evidence from case-control studies and experimental assays can provide the information necessary to confirm the endocrine effects of these chemicals in the pathophysiology of dry eye disease. We hypothesize that endocrine disruptors may contribute to the increase of ocular diseases, such as dry eye disease, in recent years.