Role of matrix metalloproteinases in uveoscleral outflow

Prostaglandin derivatives form the most widely used medicinal treatments given to glaucoma patients to lower intraocular pressure. Prostaglandins are believed to increase matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) activity, leading to increased in aqueous outflow, via uveoscleral outflow pathway. However, the direct impact of MMPs on the tissues within uveoscleral pathway has not been determined. The aim of this project was to compare the direct effect of prostaglandins and MMPs on the tissues within the uveoscleral outflow pathway. To determine the effect of known inducers of MMP activity, scleral fibroblasts and ciliary muscle cells were cultured in the presence of interleukin-1a, tumour necrosis factor, transforming growth factor p and prostaglandin F2a (PGF2a). The effect of prostaglandin F2a and MMPs on the uveoscleral pathway tissue i.e. sclera, was assessed as a measure of permeability, molecular and supramolecular scleral collagen integrity and proteoglycan composition. A significant induction of MMP 1, 2, 3 and 9 secretion and activity with cytokines and PGF2a, within human scleral fibroblast and ciliary muscle cell cultures (p<0.05). A 3-fold increase in scleral permeability was observed within 24 hour of incubation in PGF2a, whereas upto 10-fold increase was observed in MMP treated. The helical rise per residue (at 1.5nm), lateral packing (at 0.29nm) and D-spacing (at 66nm) of scleral collagen was unaffected by MMP and PGF2a incubation. Significant change in aggrecan degradation was observed within scleral tissue incubated in MMP and PGF2a (p<0.05). However, no significant change in small leucine rich proteoglycans i.e. biglycan, decorin and lumican, within sclera occurred within sclera incubated in MMP or PGF2a.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Role of matrix metalloproteinases in uveoscleral outflow

Prostaglandin derivatives form the most widely used medicinal treatments given to glaucoma patients to lower intraocular pressure. Prostaglandins are believed to increase matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) activity, leading to increased in aqueous outflow, via uveoscleral outflow pathway. However, the direct impact of MMPs on the tissues within uveoscleral pathway has not been determined. The aim of this project was to compare the direct effect of prostaglandins and MMPs on the tissues within the uveoscleral outflow pathway. To determine the effect of known inducers of MMP activity, scleral fibroblasts and ciliary muscle cells were cultured in the presence of interleukin-1a, tumour necrosis factor, transforming growth factor p and prostaglandin F2a (PGF2a). The effect of prostaglandin F2a and MMPs on the uveoscleral pathway tissue i.e. sclera, was assessed as a measure of permeability, molecular and supramolecular scleral collagen integrity and proteoglycan composition. A significant induction of MMP 1, 2, 3 and 9 secretion and activity with cytokines and PGF2a, within human scleral fibroblast and ciliary muscle cell cultures (p<0.05). A 3-fold increase in scleral permeability was observed within 24 hour of incubation in PGF2a, whereas upto 10-fold increase was observed in MMP treated. The helical rise per residue (at 1.5nm), lateral packing (at 0.29nm) and D-spacing (at 66nm) of scleral collagen was unaffected by MMP and PGF2a incubation. Significant change in aggrecan degradation was observed within scleral tissue incubated in MMP and PGF2a (p<0.05). However, no significant change in small leucine rich proteoglycans i.e. biglycan, decorin and lumican, within sclera occurred within sclera incubated in MMP or PGF2a

Effect of a home visit-based low vision rehabilitation intervention on visual function outcomes: an exploratory randomized controlled trial

Purpose: To examine the effect of a home visit–based visual rehabilitation intervention on: (1) self-reported visual function and (2) depression, wellbeing, loneliness, adjustment to visual loss, and generic health-related quality of life. Methods: In an exploratory, assessor-masked, individually randomized, single-center controlled trial, 67 participants (age: 75.22 ± 16.21 years) with low vision were allocated either to receive the home visit–based visual rehabilitation intervention (n = 35) or to a waiting list control arm (n = 32). Outcome measures were collected by telephone interview at baseline and 6 months later. The primary outcome measure was the 48-item Veterans Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-48). Secondary outcome measures were: the Patient Health Questionnaire; the Warwick-Edinburgh Mental Well-being Scale, the Adjustment to Age-related Visual Loss Scale, the standardized health-related quality of life questionnaire, and the University of California, Los Angeles Loneliness Scale. Questionnaire scores at follow-up were analyzed using analysis of covariance, controlling for the baseline score and the variables, age, number of comorbidities, visual acuity, and baseline wellbeing score. Results: Visual function (VA LV VFQ-48) improved at follow-up in both groups, with a significantly greater improvement demonstrated by the intervention group (95% confidence interval, 0.33–0.68 logits, P = 0.031), with a moderate effect size (0.55). Secondary outcomes did not indicate any statistically significant differences between groups. Conclusions: The study provides preliminary evidence that a home visit–based visual rehabilitation intervention has a positive influence on vision-related functional outcomes. A larger trial with an expanded intervention to include a mental health component and cost-effectiveness analysis is needed

Effect of rehabilitation worker input on visual function outcomes in individuals with low vision: study protocol for a randomised controlled trial

BACKGROUND: Visual Rehabilitation Officers help people with a visual impairment maintain their independence. This intervention adopts a flexible, goal-centred approach, which may include training in mobility, use of optical and non-optical aids, and performance of activities of daily living. Although Visual Rehabilitation Officers are an integral part of the low vision service in the United Kingdom, evidence that they are effective is lacking. The purpose of this exploratory trial is to estimate the impact of a Visual Rehabilitation Officer on self-reported visual function, psychosocial and quality-of-life outcomes in individuals with low vision. METHODS/DESIGN: In this exploratory, assessor-masked, parallel group, randomised controlled trial, participants will be allocated either to receive home visits from a Visual Rehabilitation Officer (n = 30) or to a waiting list control group (n = 30) in a 1:1 ratio. Adult volunteers with a visual impairment, who have been identified as needing rehabilitation officer input by a social worker, will take part. Those with an urgent need for a Visual Rehabilitation Officer or who have a cognitive impairment will be excluded. The primary outcome measure will be self-reported visual function (48-item Veterans Affairs Low Vision Visual Functioning Questionnaire). Secondary outcome measures will include psychological and quality-of-life metrics: the Patient Health Questionnaire (PHQ-9), the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Adjustment to Age-related Visual Loss Scale (AVL-12), the Standardised Health-related Quality of Life Questionnaire (EQ-5D) and the UCLA Loneliness Scale. The interviewer collecting the outcomes will be masked to the group allocations. The analysis will be undertaken on a complete case and intention-to-treat basis. Analysis of covariance (ANCOVA) will be applied to follow-up questionnaire scores, with the baseline score as a covariate. DISCUSSION: This trial is expected to provide robust effect size estimates of the intervention effect. The data will be used to design a large-scale randomised controlled trial to evaluate fully the Visual Rehabilitation Officer intervention. A rigorous evaluation of Rehabilitation Officer input is vital to direct a future low vision rehabilitation strategy and to help direct government resources. TRIAL REGISTRATION: The trial was registered with ( ISRCTN44807874 ) on 9 March 2015