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Abstract Background The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression. Methods /design The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation. Discussion Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment. Trial registration ISRCTN46824140

This is a rare presentation of brain tumour in the region of the lateral geniculate nucleus (LGN) presenting as a homonymous horizontal sectoranopia (HHS). The case highlights that subtle field defects can be asymptomatic and only detected by formal perimetry. Although homonymous sectoranopia is a rare form of visual field defect, it should be recognised as a potential manifestation of potentially significant intracranial pathology. [ABSTRACT FROM AUTHOR]

Introduction: The etiology of Behçet’s disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genome-wide association studies (GWAS) have shown limited number of novel loci-associations. The rarity and unequal distribution of the disease prevalence amongst different ethnic backgrounds have hampered the use of GWAS in cohorts of mixed ethnicity and sufficient sample size. However, novel statistical approaches have now enabled GWAS in admixed cohorts. Methods: We ran a GWAS on 336 BD cases and 5,843 controls. The cases consisted of Western Europeans, Middle Eastern and Turkish individuals. Participants from the Generation R study, a multiethnic birth cohort in Rotterdam, The Netherlands were used as controls. All samples were genotyped and data was combined. Linear regression models were corrected for population stratification using Genomic Principal Components and Linear Mixed Modelling. Meta-analysis was performed on selected results previously published. Results: We identified SNPs associated at genome-wide significant level mapping to the 6p21.33 (HLA) region. In addition to this known signal two potential novel associations on chromosomes 6 and 18 were identified, yet with low minor allele frequencies. Extended meta-analysis reveal a GWS association with the IL12A variant rs17810546 on chromosome 3. Discussion: We demonstrate that new statistical techniques enable GWAS analyses in a limited sized cohort of mixed ethnicity. After implementation, we confirmed the central role of the HLA region in the disease and identified new regions of interest. Moreover, we validated the association of a variant in the IL2A gene by meta-analysis with previous work. These findings enhance our knowledge of genetic associations and BD, and provide further justification for pursuing collective initiatives in genetic studies given the low prevalence of this and other rare diseases. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a complex inflammatory disease, of unknown etiology. While disease pathogenesis remains unclear, a strong relationship between BD and HLA-B*51 has been established over the last 30 years. A number of theories exist regarding the cause of BD; however, few are able to account for the increased rates of HLA-B*51 positive individuals, particularly around the Mediterranean basin and Middle-East where the prevalence is highest. This review outlines current immunogenetic data on BD and the immunoregulatory role natural killer cells may play. It also describes the interaction of the killer immunoglobulin-like receptor - KIR3DL1 with its ligand Bw4, which is found on HLAB51. Finally, CD94/NKG2D, MICA, and ERAP are outlined with regard to their potential roles in BD. [ABSTRACT FROM AUTHOR]

Falls are an important health issue. They cause significant morbidity and mortality particularly in older people, and also have marked psychological effects on the individual. The literature focuses particularly on older adults, an age group in which both visual impairment and falls are more prevalent, as is the associated morbidity. In this review, we summarise the current literature and point to further studies which need to be undertaken. The consequences of falls are well recognised, and there has been considerable work into identifying risk factors. Changes in visual components such as visual field, acuity, contrast sensitivity and stereopsis all have a part and the co-existence of other sensory impairments certainly increases the risk of falls. However there remain considerable gaps in our knowledge of the relationship between visual loss and falls, for example in patients with diabetic eye disease. Furthermore, there is also conflicting data as to the importance of different visual components. Various interventions, such as programmed inter-disciplinary involvement, have shown promise, however these need further confirmation of their efficacy and cost effectiveness. An added confounder may be that an intervention (eg, cataract extraction) paradoxically affects an individual's future activity level and behaviour, thereby increasing the risk of falling. With an ageing population the importance of this topic is likely to increase, as will the potential benefits of optimising our assessment and management of these patients. [ABSTRACT FROM AUTHOR]

Purpose: Assessing disease activity in Birdshot uveitis can be challenging. The peak time of the 30 Hz flicker photopic electroretinogram (ERG) was shown to be sensitive for detecting retinal dysfunction. ERG testing is not readily available in many eye units. We investigated use of a portable device to obtain recordings in the clinic setting and compared these with conventional recordings. Methods: Patients underwent testing with the portable device (RETeval, LKC Technologies) and conventional equipment (Espion ColorDome, Diagnosys). For portable recordings pupils were undilated and skin electrodes used; for conventional recordings a conductive fibre electrode was used with mydriasis. Flicker ERG peak times were recorded and were deemed abnormal if they exceeded the 95th centile from a healthy cohort (>190 healthy volunteers). Results: 18 patients with Birdshot uveitis underwent recordings. Recordings with the portable device took c. 3 min and were well‐tolerated. Mean (SD) age was 56.3 (12.8) years. For portable recordings, mean (SD) peak times were 30.1 (3.7) and 30.2 (3.9) ms for right and left eyes respectively. For conventional recordings mean (SD) peak times were 31.4 (3.9) and 31.8 (4.0) ms respectively. Peak times were significantly shorter with the portable device (p = 0.026 and 0.002 for right and left eyes). Correlation between devices was high (0.83 and 0.89 for right and left eyes) and highly significant (p < 0.0001). Strength of agreement between the two methods was good (kappa statistic 0.64; 95% CI, 0.36‐0.92). Conclusions: Correlation between the portable and conventional ERG recordings was high with a good level of agreement. Recordings were rapid and well‐tolerated. There were significant differences in peak times between the two methods highlighting the importance of normative data specific to each device. [ABSTRACT FROM AUTHOR]

Purpose: The flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals., Methods: Non-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers. At one center (group 1), the stimuli (85 Td·s, 850 Td background) delivered retinal illuminance equivalent to international standards; at the other center (group 2), a different protocol was used (32 Td·s, no background). Patients also underwent international standard flicker ERG recordings with conventional electrodes following mydriasis. Portable ERGs from patients were also compared with those from healthy individuals., Results: Thirty-two patients with BCR (mean age ± SD, 56.4 ± 11.3 years) underwent recordings. Portable and standard ERG parameters correlated strongly (r > 0.75, P < 0.01) in both groups. Limits of agreement for peak times were tighter in group 1 (n = 21; -4.3 to +2.0 ms [right eyes], -3.9 to 1.5 ms [left eyes]) than in group 2 (n = 11; -3.4 to +6.9 ms [right eyes], -4.8 to +9.0 ms [left eyes]). Compared with healthy controls (n = 66 and n = 90 for groups 1 and 2, respectively), patients with BCR showed smaller mean amplitudes and longer peak times., Conclusions: Portable ERGs correlated strongly with conventional recordings, suggesting potential in rapid assessment of cone system function in office settings., Translational Relevance: Flicker ERGs, known to be useful in BCR, can be obtained rapidly with a portable device with skin electrodes and natural pupils.

The BTS clinical statement for the diagnosis and management of ocular tuberculosis (TB) draws on the expertise of both TB and and ophthalmic specialists to outline the current understanding of disease pathogenesis, diagnosis and management in adults. Published literature lacks high-quality evidence to inform clinical practice and there is also a paucity of data from animal models to elucidate mechanisms of disease. However, in order to improve and standardise patient care, this statement provides consensus points with the currently available data and agreed best practice., Competing Interests: Competing interests: Funding has been declared from: DC, Insmed; OMK Boehringer Ingelheim, Oxford Immunotech, Cepheid, Qiagen; alal other authors have no declared interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 35-year-old woman presented with a constellation of systemic symptoms: rashes, weight loss, arthralgia and mouth ulcers. Six months afterwards, she experienced bilateral and sequential reduction in vision, and was found to have bilateral vaso-occlusive retinopathy, with critical macular ischaemia in the left eye. Her serological markers were consistent with a diagnosis of lupus. A lymph node biopsy confirmed Kikuchi-Fujimoto disease, a benign condition of unknown cause characterised by fever, cervical and axillary lymphadenopathy. Given that this overlap syndrome was associated with a number of systemic features and had affected the eyes, an immunosuppressive regime with rituximab was considered prudent. This rendered her vasculitis stable and non-progressive, and there were signs of partial retinal microvasculature recovery on optical coherence tomography angiography. There is increasing evidence of an overlap between Kikuchi-Fujimoto disease and systemic lupus erythematosus, which is associated with vaso-occlusive retinopathy. In these instances, a multidisciplinary approach is warranted, with consideration of appropriate treatment in order to prevent harmful sequelae of vasculitis. Our treatment with rituximab abated the disease process, although close follow-up is paramount to monitor results and side-effects of treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS., Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included., Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A., Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.

Objectives: Patients with Behçet's disease (BD) constantly complain of fatigue and many have problems with poor sleep. This ultimately has a major impact on all aspects of normal living. To attempt to understand this, Artificial Intelligence (AI) was used to identify potential biomarkers. These were alpha-melanocyte stimulating hormone (α-MSH), vasoactive intestinal peptide (VIP) and some inflammatory cytokines. We assessed the association of fatigue, quality of sleep and disease activity with circulating concentration of α-MSH, VIP and inflammatory cytokines., Methods: There were 127 participants, 97 BD patients, and 30 healthy controls (HC). All completed the Multi-Dimensional Assessment of Fatigue questionnaire (MAF) and the Pittsburgh Sleep Quality Index (PSQI) on the day of their clinical assessment. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum concentrations of α-MSH, VIP and cytokines (IL-1β, IL-6, IL-10, and TNF-α)., Results: 64% of BD patients experienced high fatigue scores, and 63% had poor quality of sleep. When BD and HC were compared the MAF and PSQI scores as well as the serum concentrations of α-MSH, VIP, and IL-6 were significantly higher in BD (p values were: 0.001, 0.001, 0.001, 0.004 and 0.036, respectively). Both α-MSH and IL-6 had significant impact on MAF and PSQI. Interestingly, VIP had a significant influence on PSQI and disease activity, but not on MAF., Conclusions: A better understanding of these complex clinical and biochemical interactions between α-MSH, VIP and IL-6 might lead to the development of novel approaches to manage fatigue and sleep disorders as well as disease activity in BD patients.

Purpose: The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms., Methods: This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or a waiting-list control arm. PST is a manualized talking intervention delivered by a trained therapist who teaches people over six to eight sessions to implement a seven-step method for solving their problems. Referral to the physician involved sending a referral letter to the person's physician, encouraging him or her to consider treatment according to the stepped care protocol recommended by the U.K.'s National Institute of Health and Care Excellence. The primary outcome was change in depressive symptoms (6 months after baseline) as determined by the Beck Depression Inventory., Results: At 6 months, Beck Depression Inventory scores reduced by 1.05 (SD 8.85), 2.11 (SD 7.60), and 2.68 (SD 7.93) in the waiting-list control, referral, and PST arms, respectively. The cost per patient of the PST intervention was £1176 in Wales and £1296 in London., Conclusions: Depressive symptoms improved most in the PST group and least in the control group. However, the change was small and the uncertainty of the measurements relatively large.

Background: Acute toxoplasma retinochoroiditis causes transient symptoms of ocular discomfort and may lead to permanent visual loss. Antibiotic treatment aims primarily to reduce the risk of permanent visual loss, recurrent retinochoroiditis, and the severity and duration of acute symptoms. There is uncertainty about the effectiveness of antibiotic treatment., Objectives: To compare the effects of antibiotic treatment versus placebo or no treatment for toxoplasma retinochoroiditis., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2016, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2016), EMBASE (January 1980 to February 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 February 2016. We searched the reference lists of identified articles and contacted pharmaceutical companies for unpublished trials., Selection Criteria: We included randomised controlled trials that compared any antibiotic treatment against placebo or no treatment. We excluded trials that included immunocompromised participants. We considered any antibiotic treatment known to be active against Toxoplasma gondii. Antibiotic treatment could be given in any dose orally, by intramuscular injection, by intravenous infusion, or by intravitreal injection., Data Collection and Analysis: The primary outcomes for this review were visual acuity at least three months after treatment and risk of recurrent retinochoroiditis. Secondary outcomes were improvement in symptoms and signs of intraocular inflammation, size of lesion, and adverse events. We used standard methodological procedures expected by Cochrane., Main Results: Four trials that randomised a total of 268 participants met the inclusion criteria. In all four studies antibiotic was administered orally.One study conducted in Brazil in both adults and children compared trimethoprim-sulfamexacocol over 20 months to no treatment and was judged to be at high risk of performance, detection, and attrition bias. The other three studies compared antibiotic treatment to placebo. We judged these three studies to be at a mixture of low or unclear risk of bias due to poor reporting. One study conducted in the US in adults studied pyrimethamine-trisulfapyrimidine for eight weeks; one study conducted in the UK in children and adults evaluated pyrimethamine for four weeks; and one study conducted in Brazil in adults investigated trimethoprim-sulfamethoxazole for 12 months. In the last study, all participants had active retinochoroiditis and were treated with antibiotics for 45 days prior to randomisation to trimethoprim-sulfamethoxazole versus placebo.Only the study in Brazil of trimethoprim-sulfamethoxazole over 12 months, in participants with healed lesions, reported the effect of treatment on visual acuity. People treated with antibiotics may have a similar change in visual acuity compared with people treated with placebo at one year (mean difference -1.00 letters, 95% confidence interval (CI) -7.93 to 5.93 letters; 93 participants; low-quality evidence).Treatment with antibiotics probably reduces the risk of recurrent retinochoroiditis compared with placebo (risk ratio (RR) 0.26, 95% CI 0.11 to 0.63; 227 participants; 3 studies; I(2) = 0%; moderate-quality evidence); similar results were seen for acute and chronic retinochoroiditis.The UK study of pyrimethamine for four weeks reported an improvement in intraocular inflammation in treated compared with control participants (RR 1.76, 95% CI 0.98 to 3.19; 29 participants; low-quality evidence). The study in Brazil of trimethoprim-sulfamethoxazole for 12 months stated that the severity of inflammation was higher in the comparator group when compared to the antibiotic-treated group but did not provide further details. In the US study of pyrimethamine-trisulfapyrimidine for eight weeks intraocular inflammation had almost completely resolved by eight weeks in all participants, however in this study all participants received steroid treatment.Two studies (UK and US studies) reported an increased risk of adverse events in treated participants. These were a fall in haemoglobin, leucocyte, and platelet count, nausea, loss of appetite, rash, and arthralgia., Authors' Conclusions: Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. Further trials of people with acute and chronic toxoplasma retinochoroiditis affecting any part of the retina are required to determine the effects of antibiotic treatment on visual outcomes.

Purpose: To determine whether the volume of retinal tissue passing between the inner and outer retina in macular edema could be used as an indicator of visual acuity., Methods: Diabetic and uveitic patients with cystoid macular edema (81 subjects, 129 eyes) were recruited. Best corrected logMAR visual acuity and spectral optical coherence tomography (OCT/SLO; OTI, Toronto, ONT, Canada) were performed in all patients. Coronal OCT scans obtained from a cross section of the retina between the plexiform layers were analyzed with a grid of five concentric radii (500, 1000, 1500, 2000, and 2500 μm centered on the fovea). The images were analyzed to determine the amount of retinal tissue present within each ring. A linear regression model was developed to determine the relationship between tissue integrity and logMAR visual acuity., Results: A linear relationship between tissue integrity and VA was demonstrated. The volume of retinal tissue between the plexiform layers in rings 1 and 2 (up to 1000 μm from the foveal center) predicted 80% of visual acuity. By contrast, central macular thickness within the central 1000 μm predicted only 14% of visual acuity., Conclusions: This study showed that the cross-sectional area of retinal tissue between the plexiform layers in cystoid macular edema, as imaged by OCT, is the best indicator of visual function at baseline. Further prospective treatment trials are needed to investigate this parameter as a predictor of visual outcome after intervention.

Purpose: To investigate whether polymorphisms in the gene encoding the chemokine receptor CX3CR1, which has been linked to changes in functional ligand-binding activity, are associated with retinal vasculitis (RV) in a cohort of patients in the United Kingdom., Methods: DNA was prepared from whole blood of 126 patients with RV and 95 healthy individuals by a standard salting-out procedure. Two polymorphisms, V249I and T280M, were analyzed by multiplex polymerase chain reaction-sequence-specific primers (PCR-SSPs)., Results: There was no significant difference between the prevalence of V249 or I249 variants in patients with RV or in control subjects. By contrast, the 280M variant was significantly raised in patients compared with control subjects (P=0.01), the IV/MT haplotype was also more prevalent in patients with RV than in control subjects (P=0.006), and the I249/M280 haplotype was associated with retinal vasculitis (P=0.01). The 280M variant was significantly associated with the nonischemic form of RV compared with healthy control subjects (P=0.009)., Conclusions: Polymorphisms related to a functional decrease in ligand binding activity of CX3CR1 are associated with disease in U.K. patients with retinal vasculitis. CX3CR1 and its ligand CX3CL1 have been implicated in leukocyte adhesion and neuronal protection. Changes in the activity of this interaction may have a role in the pathogenesis of RV.

Purpose: To undertake safety testing of infracyanine green (IFCG) in a cell culture model., Methods: Experiments were undertaken in a cell culture model used previously to perform safety testing of indocyanine green (ICG). Human retinal pigment epithelium (RPE) and Müller cells were exposed to IFCG for 5 minutes, over a range of concentrations up to 0.5%. Experiments were repeated, using double-staining with trypan blue. Cell viability was measured at days 1, 5, and 15 using a mitochondrial dehydrogenase assay and a fluorescent live-dead probe containing calcein and ethidium homodimer-1. Viability was measured after exposure to 0.5% IFCG and 5 minutes of illumination with a vitrectomy endolight powered by a xenon light source., Results: RPE viability was not reduced over the range of concentrations and follow-up intervals. RPE cells exposed to IFCG and illumination had reduced viability relative to the negative control (cells exposed to saline), but not relative to those exposed to saline and illumination. Glial cells showed reduced viability at days 1 and 5, but not day 15. Illumination did not further reduce viability., Conclusions: IFCG has been advocated as a safer macular vital stain than ICG. These results suggest that it is less likely to produce phototoxicity, but despite being nearly iso-osmolar, IFCG also produces damage in cultured glial cells.

Purpose: Indocyanine green (ICG) and trypan blue have been advocated as vital stains for use during macular surgery. The safety of these agents was tested using a cell culture model., Methods: Human retinal pigment epithelium (RPE) and Müller cell lines were exposed to ICG over a range of concentrations up to 0.5%, and trypan blue up to 0.2%. Cells were exposed to each dye for 5, 15, or 30 minutes, rinsed, and incubated 24 hours. Cell viability was measured using a mitochondrial dehydrogenase-assay and fluorescent live-dead probe. Experiments were repeated using 0.5% and 1% ICG and 0.06% and 0.12% trypan blue, with follow-up at 0, 1, 5, and 15 days. ICG experiments were repeated in the presence of illumination from a xenon light-source channeled through a surgical endolight, and using reduced osmolarity solutions of 0.1%, 0.5%, and 1% (185 vs. 275 mOsM)., Results: There was no clear relationship between cell viability and the concentration of the agent or duration of follow-up, except in RPE cells exposed to 1% ICG. These showed a linear (R(2) 0.9952) decline in viability with time, with a significant reduction by day 15 (P = 0.016). RPE cells exposed to ICG and illumination were not significantly different from the negative control, but when illumination was combined with low osmolarity, viability was reduced (P = 0.0016). ICG and illumination reduced Müller cell viability (P < 0.0001 for both 185 and 275 mOsM). Müller cells incubated with 185 mOsM 1% ICG showed a significant reduction in viability (P < 0.0001) not seen with the 185 mOsM 0.5% or 0.1% solutions or in the low-osmolarity RPE groups., Conclusions: The combination of exposure to 0.5% ICG and the newer endoillumination light-sources can damage cultured Müller cells. Although the preparations of ICG most commonly used clinically did not produce significant damage, relatively small changes in ICG osmolarity and concentration did. This suggests that safety margins are not large. Trypan blue is safe in a cell culture model.