The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

Incidence of hypotony and sympathetic ophthalmia following trans scleral cyclophotocoagulation for glaucoma and a report of risk factors

Background: To report the incidence and risk factors for hypotony and estimate the risk of sympathetic ophthalmia following diode laser trans-scleral cyclophotocoagulation (TSCPC). Design: Retrospective study using data from a private tertiary glaucoma clinic and review of the literature. Participants: Seventy eyes of 70 patients with refractory glaucoma who received TSCPC treatment. Methods: Review of the records of consecutive patients who underwent TSCPC by a single ophthalmic surgeon and review of the literature. Main Outcome Measures: Hypotony (including phthisis bulbi), sympathetic ophthalmia. Results: Seven eyes (10%; CI 5-19%) developed hypotony and included 4 eyes that developed phthisis. Higher total energy delivered during TSCPC treatment was associated with an increased risk of hypotony: eyes that developed hypotony received a mean total energy of 192.5 ± 73.2 joules, compared to a mean of 152.9 ± 83.2 joules in hypotony-free cases. The difference in mean energy delivered between the hypotony and non-hypotony group was 38.53 (95% CI: -27.57 to 104.63). The risk of sympathetic ophthalmia estimated from a review of the published literature and current series was one in 1512, or 0.07% (CI 0.03% - 0.17%). Conclusions: Total laser energy is one of several risk factors that act in a sufficient component cause-model to produce hypotony in an individual patient. The small sample size precluded inference for other individual putative risk factors but titrating laser energy may help decrease the occurrence of hypotony. The risk of sympathetic ophthalmia calculated from the literature is likely an overestimate caused by publication bias.

Nurses' experiences of practice and political reform in long-term aged care in Australia : implications for the retention of nursing personnel

Keywords gerontological nursing;health care reform;health policy;long-term care;recruitment and retention Aim  The aim of the study was to explore registered nurses’ experiences in long-term aged care in light of the political reform of aged care services in Australia. Background  In Australia, the aged care industry has undergone a lengthy period of political and structural reform. Despite reviews into various aspects of these reforms, there has been little consideration of the effect these are having on the practice experiences and retention of nursing staff in long-term care. Methods  In this critical hermeneutic study, 14 nurses from long-term care facilities in Australia were interviewed about their experiences during the reform period. Results  The data revealed a sense of tension and conflict between nurses’ traditional values, roles and responsibilities and those supported by the reforms. Nurses struggled to renegotiate both their practice roles and values as the reforms were implemented and the system evolved. Nursing management support was an important aspect in mediating the effect of reforms on nursing staff. Conclusion  This research highlights both the tensions experienced by nurses in long-term aged care in Australia and the need to renegotiate nursing roles, responsibilities and values within an evolving care system. This research supports a role for sensitive and proactive nursing management during periods of industry reform as a retention strategy for qualified nursing personnel.

Searching for value : the influence of policy and reform on nurses’ sense of value in long-term aged care in Australia.

Contemporary literature on long-term aged care focuses heavily on issues associated with the recruitment and retention of nursing staff, such as job satisfaction and attitudes towards caring for older people. This paper aims to highlight one aspect of a larger study of registered nurses' experiences in long-term aged care in Australia and the influence that government policy and reform has in shaping that experience. This insight into aspects of nurses' everyday experience also contributes to a broader understanding of job satisfaction in long-term care. Findings from this study suggest that registered nurses experience tension in their search for value in their practice, which incorporates professional, political and social mediators of value and worth. These issues are discussed in relation to the impact of policy and reform on nurses' sense of value in long-term aged care and highlight the need for sensitive policy initiatives that support issues of value in nursing practice.

An observational study of nutrition and physical activity behaviours, knowledge, and advice in pregnancy

Maternal obesity, excess weight gain and lifestyle behaviours during pregnancy have been associated with future overweight and other adverse health outcomes for mothers and babies. This study compared the nutrition and physical activity behaviours of Australian healthy (BMI ≤ 25 k/m2) and overweight (BMI ≥ 25 kg/m2) pregnant women and described their knowledge and receipt of health professional advice early in pregnancy. Methods Pregnant women (n=58) aged 29±5 (mean±s.d.) years were recruited at 16±2 weeks gestation from an Australian metropolitan hospital. Height and weight were measured using standard procedures and women completed a self administered semi-quantitative survey. Results Healthy and overweight women had very similar levels of knowledge, behaviour and levels of advice provided except where specifically mentioned. Only 8% and 36% of participants knew the correct recommended daily number of fruit and vegetable serves respectively. Four percent of participants ate the recommended 5 serves/day of vegetables. Overweight women were less likely than healthy weight women to achieve the recommended fruit intake (4% vs. 8%, p=0.05), and more likely to consume soft drinks or cordial (55% vs 43%, p=0.005) and take away foods (37% vs. 25%, p=0.002) once a week or more. Less than half of all women achieved sufficient physical activity. Despite 80% of women saying they would have liked education about nutrition, physical activity and weight gain, particularly at the beginning of pregnancy, less than 50% were given appropriate advice regarding healthy eating and physical activity. Conclusion Healthy pregnancy behaviour recommendations were not being met, with overweight women less likely to meet some of the recommendations. Knowledge of dietary recommendations was poor and health care professional advice was limited. There are opportunities to improve the health care practices and education pregnant women received to improve knowledge and behaviours. Pregnant women appear to want this.

The increased risks of death and extra lengths of hospital and ICU stay from hospital-acquired bloodstream infections : a case-control study

Objectives Hospital-acquired bloodstream infections are known to increase the risk of death and prolong hospital stay, but precise estimates of these two important outcomes from well-designed studies are rare, particularly for non-intensive care unit (ICU) patients. We aimed to calculate accurate estimates, which are vital for estimating the economic costs of hospital-acquired bloodstream infections.

The interface of acute and aged care : the role of the nurse in a provincial area

Objective This study was to investigate issues that arose from pre-admission to post-discharge, for people in Toowoomba, Queensland over the age of 65 admitted to an acute facility. This paper concentrates on a significant concern that emerged from the large amount of data collected during this project, that is,the role of the nurse in the continuum of health care involving elderly people. Method The study involved a multi-site, multi-agency and multi-method (qualitative and quantitative) approach. Data was collected from regional service providers, the Department of Health and Aged Care (DHAC), the Australian Bureau of Statistics (ABS), Home and Community Care (HACC), the Aged Care Assessment Team (ACAT), elderly people who had been discharged from regional hospitals and their carers, residents of regional aged care facilities, area health professionals and elderly regional hospital inpatients. Results The data indicated that nurses in this provincial area currently play a limited role in preadmission planning, being mostly concerned with elective surgery, especially joint replacements. While nurses deliver the majority of care during hospitalisation, they do not appear to be cognizant of the needs of the elderly regarding post-acute discharge. Conclusion The recent introduction of the model of nurse case management in the acute sector appears to be a positive development that will streamline and optimise the health care of the elderly across the continuum in the Toowoomba area. The paper recommends some strategies, such as discharge liaison nurses based in Emergency Departments and the expansion of the nurse case management role, which would optimise care for the elderly person at the interface of care.

Experiences of regional and rural people with cancer being treated with radiotherapy in a metropolitan centre

This paper explores the issues related to rural people with cancer whose choice of radiotherapy treatment necessitated travel and accommodation in a metropolitan centre. Semi-structured interviews with 46 participants, from the Toowoomba and Darling Downs region of Queensland, Australia, were conducted and the data thematically analysed. The specific themes identified were: being away from loved ones, maintaining responsibilities whilst undergoing treatment, emotional stress, burden on significant others, choice about radiotherapy as a treatment, travel and accommodation, and financial burden. This study supports the need for a radiotherapy centre in the location of Toowoomba as a way of providing some equity and access to such treatment for the rural people of Queensland.

Changes of mortality and causes of death from 1970 to 2005 and decomposition analysis in Shandong province [山东省1970-2005年人群死亡率极死因变化与差别分解分析]

Objective To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005,and to quantitatively estimate the influential factors. Methods Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors for the change of mortality. Results The total mortality had had a slight change since 1970s,but had increased since 1990s.However,both the mortality rates of age-adjusted and age-specific decreased significantly. The mortality of Group Ⅰ diseases including infectious diseases as well maternal and perinatal diseases decreased drastically. By contrast, the mortality of non-communicable chronic diseases (NCDs)including cardiovascular diseases(CVDs),cancer and injuries increased. The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely. Non-demographic factors were responsible for the decrease of Group Ⅰ disease and the increase of injuries. With respect to the increase of NCDs as a whole. Demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality. Nevertheless, for the increase of some leading NCD diseases as CVDs and cancer, the increase was mainly due to non-demographic rather than demographic factors. Conclusion Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect, the overall mortality in Shandong would maintain a balance or slightly rise in the coming years. Group Ⅰ diseases in Shandong had been effectively under control. Strategies focusing on disease control and prevention should be transferred to chronic diseases, especially leading NCDs, such as CVDs and cancer.

Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long–Evans rats by the α-2 adrenoreceptor antagonist yohimbine

Rationale Developing models to efficiently explore the mechanisms by which stress can mediate reinstatement of drug-seeking behavior is crucial to the development of new pharmacotherapies for alcohol use disorders. Objectives We examined the effects of multiple reinstatement sessions using the pharmacological stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a more efficient model of stress-induced reinstatement. Methods Long–Evans rats were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20% ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self-administration sessions, followed by extinction training. After reaching extinction criteria, the animals were tested once per week with yohimbine vehicle and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions or blood collection. Levels of reinstatement and plasma corticosterone (CORT) were determined each week for four consecutive weeks. Results Yohimbine induced reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks. Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol group after the first reinstatement session but remained stable for the 20% ethanol group trained without sucrose. Plasma CORT levels in response to injection of both vehicle and yohimbine were significantly higher in the ethanol-trained animals compared to sucrose controls. Conclusions The stable reinstatement in the 20% ethanol group supports the use of this training procedure in studies using within-subject designs with multiple yohimbine reinstatement test sessions. Additionally, these results indicate that the hormonal response to stressors can be altered following extinction from self-administration of relatively modest amounts of ethanol.

Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Source apportionment of airborne particulate matter : an overview of Australian and New Zealand studies

Despite the existence of air quality guidelines in Australia and New Zealand, the concentrations of particulate matter have exceeded these guidelines on several occasions. To identify the sources of particulate matter, examine the contributions of the sources to the air quality at specific areas and estimate the most likely locations of the sources, a growing number of source apportionment studies have been conducted. This paper provides an overview of the locations of the studies, salient features of the results obtained and offers some perspectives for the improvement of future receptor modelling of air quality in these countries. The review revealed that because of its advantages over alternative models, Positive Matrix Factorisation (PMF) was the most commonly applied model in the studies. Although there were differences in the sources identified in the studies, some general trends were observed. While biomass burning was a common problem in both countries, the characteristics of this source varied from one location to another. In New Zealand, domestic heating was the highest contributor to particle levels on days when the guidelines were exceeded. On the other hand, forest back-burning was a concern in Brisbane while marine aerosol was a major source in most studies. Secondary sulphate, traffic emissions, industrial emissions and re-suspended soil were also identified as important sources. Some unique species, for example, volatile organic compounds and particle size distribution were incorporated into some of the studies with results that have significant ramifications for the improvement of air quality. Overall, the application of source apportionment models provided useful information that can assist the design of epidemiological studies and refine air pollution reduction strategies in Australia and New Zealand.

Use of serum and blood samples on filter paper to improve the surveillance of dengue in Pacific Island Countries

Background In Pacific Island Countries (PICs) the epidemiology of dengue is characterized by long-term transmission of a single dengue virus (DENV) serotype. The emergence of a new serotype in one island country often indicates major outbreaks with this serotype will follow in other PICs. Objectives Filter paper (FP) cards on which whole blood or serum from dengue suspected patients had been dried was evaluated as a method for transportation of this material by standard mail delivery throughout the Pacific. Study design Twenty-two FP-dried whole blood samples collected from patients in New Caledonia and Wallis & Futuna Islands, during DENV-1 and DENV-4 transmission, and 76 FP-dried sera collected from patients in Yap State, Majuro (Republic of Marshall Islands), Tonga and Fiji, before and during outbreaks of DENV-2 in Yap State and DENV-4 in Majuro, were tested for the presence of DENV RNA, by serotype specific RT-PCR, at the Institut Louis Malardé in French Polynesia. Results The serotype of DENV could be determined, by a variety of RT-PCR procedures, in the FP-dried samples after more than three weeks of transport at ambient temperatures. In most cases, the sequencing of the envelope gene to genotype the viruses also was possible. Conclusions The serotype and genotype of DENV can be determined from FP-dried serum or whole blood samples transported over thousands of kilometers at ambient, tropical, temperatures. This simple and low-cost approach to virus identification should be evaluated in isolated and resource poor settings for surveillance for a range of significant viral diseases.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.