Mastering the canonical loop of serine protease inhibitors : enhancing potency by optimising the internal hydrogen bond network

Background Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity. Methodology/Principal Findings In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were investigated using an in silico screen of inhibitor variants in complex with KLK4 or trypsin. Substitutions favouring internal hydrogen bond formation directly correlated with increased potency of inhibition in vitro. This produced a second generation inhibitor (SFTI-FCQR Asn14) which displayed both a 125-fold increased capacity to inhibit KLK4 (Ki = 0.0386±0.0060 nM) and enhanced selectivity over off-target serine proteases. Further, SFTI-FCQR Asn14 was stable in cell culture and bioavailable in mice when administered by intraperitoneal perfusion. Conclusion/Significance These findings highlight the importance of conserving structural rigidity of the binding loop in addition to optimising protease/inhibitor contacts when re-engineering canonical serine protease inhibitors.

A double-blind randomised controlled trial of a natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer

Background: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration: ACTRN 12612000568819

Preservice teachers teaching technology with robotics

This study investigates the value of a robotics-based school engagement experience for preservice teachers enrolled in a fourth year technology education curriculum unit and analyses their perceived abilities and confidence to design and implement engaging technology activities following this experience. Technology is a key learning area in Australian schools but research shows that most teachers find this subject challenging to teach. This could be attributed to teachers’ attitudes and their lack of knowledge, hence investigating preservice teachers’ involvement with technology may provide further insights. In this study, 30 preservice teachers used robotics to implement technology activities with 22 primary school students from a school in a low socio-economic area. Surveys were administered to ascertain the preservice teachers' perceptions of their school engagement experiences. The data gathered from the participants showed that they had gained confidence and knowledge from the experience and felt the engagement activity would assist them to develop and implement technology activities in their future classrooms.

A mixed-method study to investigate the relationship between the number of social support people present during labour, women’s perceptions and birth outcomes

The birth of a baby is a significant event for women and their families, with the event being influenced by the prevailing social and cultural context. Historically, women throughout the world have given birth at home assisted by other women who helped them cope with the stress of labour and birth. In the middle of the twentieth century, the togetherness, caring and support that were provided within the social and cultural context of childbirth began to change; women in most developed countries, and to some extent in developing countries, laboured and gave birth in institutions that isolated them from the support of family and friends. This practice is referred to as the medical model of childbirth and, over time, birthing within this model has come to be viewed by women as a dehumanising experience. In an attempt to secure a more supportive experience, women began to demand the presence of a supportive companion; namely their partner. This event became the catalyst for a number of studies focusing on different types of support providers and their contribution to the phenomenon of social support during labour. More recently, it has become a common practice for some women to be supported during labour by a number of people from their social network. However, research on the influence of such supportive people on women’s experience of labour and birth and on birth outcomes is scarce. The aim of this study is to examine the influence of various support arrangements from a woman’s family and social network on her experience of labour and birth and on birth outcomes. The mixed-method study was conducted to answer three research questions: 1. Do women with more than one support person present during labour and birth have similar perceptions and experiences of support compared to women with one support person? 2. Do women with more than one support person present during labour and birth have similar birth outcomes compared to women with one support person? 3. Do women with different types of support providers during labour and birth have similar birth outcomes? Methods Phase one of this study developed, pilot tested and administered a newly developed instrument designed to measure women’s perceptions of supportive behaviours provided during labour. Specific birth outcome data were extracted from the medical records. Phase two consisted of in-depth interviews with a sample of women who had completed the survey. Results: The results identified a statistically significant relationship between women’s perceptions of social support and the number of support providers: women supported by one person only rated the supportive behaviours of that person more highly compared to women who were supported by a number of people. The results also identified that women supported by one person used less analgesia. An additional qualitative finding was that some women sacrificed the support of female relatives at the request of their partners. Conclusion: By using a mixed-method approach, this study found that women were selective in their choice of support providers, as they chose individuals with whom they had an enduring affectionate attachment. Women place more emphasis on a support person’s ability to fulfil their attachment needs of close proximity and a sense of security and safety, rather than their ability to provide the expected functional supportive behaviours.

The developmental consequences of rare chromosome disorders : two case reports

Aim: As molecular and cytogenetic testing becomes increasingly sophisticated, more individuals are being diagnosed with rare chromosome disorders. Yet despite a burgeoning knowledge about biomedical aspects, little is known about implications for psychosocial development. The scant literature gives a general impression of deficits and adverse developmental outcomes. Method: Developmental data were obtained from two 16 year olds diagnosed with a rare chromosome disorder – a girl with 8p23.1 and a boy with 16q11.2q12.1. Measures of intellectual ability, academic achievement, and other aspects of functioning were administered at multiple time points from early childhood to adolescence. Results: Both adolescents experienced initial delays in motor and language development. Although the girl’s intelligence is assessed as being in the average range, she experiences difficulties with motor planning, spelling and writing. The boy has been diagnosed with a mild intellectual disability and demonstrates mild autistic features. Conclusions: The two case descriptions are in marked contrast to the published literature about these two chromosome anomalies. Both adolescents are developing much more positively than would be expected on the basis of the grim predictions of their paediatricians and the negative reports in the literature. It is concluded that, for most rare chromosome disorders, the range of possible developmental outcomes is currently unknown.

Assessing intellectual functioning in young adolescents : how do the WISC-IV and SB5 compare?

The Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) and the Stanford-Binet – Fifth Edition (SB5) are two of the most commonly used intelligence tests for children and adolescents. No comparative studies of the WISC-IV and SB5 have yet been published. In the current study the WISC-IV and SB5 were administered in counterbalanced order to 30 typically-developing 12- to 14-year-old adolescents. There was a significant difference between Full Scale IQs on the two measures, with scores being higher on the WISC-IV. A significant difference was also found between Verbal IQs and there were large score differences for some participants. The paper concludes that the WISC-IV and SB5 cannot be presumed to be interchangeable measures of intelligence.

Identifying engaging features of schooling : assessing the psychometric soundness of student generated research

In this article we report on data analysed from a student project about attitudes to school and student perception of engagement and disengagement. The data were collected by students in an Australian study that employed the Young People as Researchers Model. Middle years students devised and administered a questionnaire to students in grade eight, nine and ten at a secondary school in Australia. A total of 239 students completed the questionnaire. The students completed the initial analysis which was followed by a more detailed analysis by the authors of this paper. The findings support the work of American, British and Australian researchers about the factors that influence engagement and disengagement from schooling. The reported outcomes from the student work and the secondary analysis indicate that students do have the capacity to undertake valid and meaningful research and can make informed contributions to school improvement and student engagement.

Educational stress among Chinese adolescents : measurement, risk factors and associations with mental health

Academic pressure among adolescents is a major risk factor for poor mental health and suicide and other harmful behaviours. While this is a worldwide phenomenon, it appears to be especially pronounced in China and other East Asian countries. Despite a growing body of research into adolescent mental health in recent years, the multiple constructs within the ‘educational stress’ phenomenon have not been clearly articulated in Chinese contexts. Further, the individual, family, school and peer influencing factors for educational stress and its associations with adolescent mental health are not well understood. An in-depth investigation may provide important information for the ongoing educational reform in Mainland China with a special focus on students’ mental health and wellbeing. The primary goal of this study was to examine the relative contribution of educational stress to poor mental health, in comparison to other well-known individual, family, school and peer factors. Another important task was to identify significant risk factors for educational stress. In addition, due to the lack of a culturally suitable instrument for educational stress in this population, a new tool – the Educational Stress Scale for Adolescents (ESSA) was initially developed in this study and tested for reliability and validity. A self-administered questionnaire was used to collect information from convenient samples of secondary school students in Shandong, China. The pilot survey was conducted with 347 students (grades 8 and 11) to test the psychometric properties of the ESSA and other scales or questions in the questionnaire. Based on factor analysis and reliability and validity testing, the 16-item scale (the ESSA) with five factors showed adequate to good internal consistency, 2-week test-retest reliability, and satisfactory concurrent and predictive validity. Its factor structure was further demonstrated in the main survey with a confirmatory factor analysis illustrating a good fit of the proposed model based on a confirmatory factor analysis. The reliabilities of other scales and questions were also adequate to be used in this study. The main survey was subsequently conducted with a sample of 1627 secondary school (grades 7-12) students to examine the influencing factors of educational stress and its associations with mental health outcomes, including depression, happiness and suicidal behaviours. A wide range of individual, family, school and peer factors were found to have a significant association with the total ESSA and subscale scores. Most of the strong factors for academic stress were school or study-related, including rural school location, low school connectedness, perceived poor academic grades and frequent emotional conflicts with teachers and peers. Unexpectedly, family and parental factors, such as parental bonding, family connectedness and conflicts with parents were found to have little or no association with educational stress. Educational stress was the most predictive variable for depression, but was not strongly associated with happiness. It had a strong association with suicide ideation but not with suicide attempts. Among five subscales of the ESSA, ‘Study despondency’ score had the strongest associations with these mental health measures. Surprising, two subscales, ‘Self-expectation’ and ‘Worry about grades’ showed a protective effect on suicidal behaviours. An additional analysis revealed that although academic pressure was the most commonly reported reason for suicidal thinking, the occurrence of problems in peer relationships such as peer teasing and bullying, and romantic problems had a much stronger relationship with actual attempts. This study provides some insights into the nature and health implications of educational stress among Chinese adolescents. Findings in this study suggest that interventions on educational stress should focus on school environment and academic factors. Intervention programs focused on educational stress may have a high impact on the prevalence of common mental disorders such as depression. Efforts to increase perceived happiness however should cover a wider range of individual, family and school factors. The importance of healthy peer relationships should be adequately emphasised in suicide prevention. In addition, the newly developed scale (the ESSA) demonstrates sound psychometric properties and is expected to be used in future research into academic-related stress among secondary school adolescents.

The "free-factor" impact on value in health services

Purpose - This paper seeks to understand the impact of financial cost on customer value in health prevention services by comparing free government services with private fee-charging providers. This is important as there is a common belief that a free health service is of lower quality and thus lower value than a paid service. However there is no evidence to verify this notion. Design / Methodology / Approach - A large-scale online survey was administered nationwide to Australian women. The respondents were asked about the functional and emotional value derived from their service experiences. Findings - Structural equation modelling (SEM) revealed non significant relationships between fee/free services and functional and emotional value (FV/EV). The non-significant relationship with FV is contrary to the theory of price quality relationship in services. This could be attributed to consumer perceptions that the technical quality of health professionals is comparable across free and paid services. The non-significant relationship with EV could be explained by the indicators used to reflect EV. These indicators were reflective of breast screening behaviour, not breast screening services. Subsequently, it may be posited that the act of having a breast screen is sufficient for consumers to derive emotional value, regardless of the financial cost. Originality / Value - This research fills an important gap in the literature by investigating the impact of financial cost on a service that consumers use proactively(prevention), rather than reactively (treatment). Insights are provided into the impact of cost on customer value in preventive health services, which are valuable to social marketing academics, health practitioners, and governments

The experiences of parents and other supervisors in a graduated driver licensing program in Queensland, Australia

Study Aims Describe how parents and other private supervisors have responded to the changes made to the Queensland graduated driver licensing system in mid-2007 Examine differences in the experiences and perceptions of the parents and non-parents Method Combination of convenience and snowball sampling Survey administered by the internet Survey conducted between July 2009 and May 2010 Approximately 15-20 minutes to complete $20 reimbursement for participation

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine : involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.

Impact of physical, psychological, and sexual violence on social adjustment of school children in India

and sexual violence on the social adjustment of Grade 8 and 9 school children in the state of Tripura, India. The study participants, 160 boys and 160 girls, were randomly selected from classes in eight English and Bengali medium schools in Agartala city, Tripura. Data were collected using a self-administered Semi-structured Questionnaire for Children/Students and a Social Adjustment Inventory which were custom-made for the study based on measures in the extant research adapted for the Indian context. Findings revealed that students experienced physical (21.9%), psychological (20.9%), and sexual (18.1%) violence at home, and 29.7% of the children had witnessed family violence. Boys were more often victims of physical and psychological violence while girls were more often victims of sexual violence. The social adjustment scores of school children who experienced violence, regardless of the nature of the violence, was significantly lower when compared with scores of those who had not experienced violence (p<0.001). Social adjustment was poorer for girls than boys (p<0.001). The study speaks in favour of early detection and intervention for all child maltreatment subtypes and for children exposed to interparental violence, and highlights the crucial role of schools and school psychology in addressing the problem.

Birth outcomes after spontaneous or assisted conception among infertile Australian women aged 28 to 36 years: A prospective, population-based study

Objective To examine the extent to which the odds of birth, pregnancy, or adverse birth outcomes are higher among women aged 28 to 36 years who use fertility treatment compared with untreated women. Design Prospective, population-based. Setting Not applicable. Patient(s) Participants in the ALSWH born in 1973 to 1978 who reported on their infertility and use of in vitro fertilization (IVF) or ovulation induction (OI). Intervention(s) Postal survey questionnaires administered as part of ALSWH. Main Outcome Measure(s) Among women treated with IVF or OI and untreated women, the odds of birth outcomes estimated by use of adjusted logistic regression modeling. Result(s) Among 7,280 women, 18.6% (n = 1,376) reported infertility. Half (53.0%) of the treated women gave birth compared with 43.8% of untreated women. Women with prior parity were less likely to use IVF compared with nulliparous women. Women using IVF or OI, respectively, were more likely to have given birth after treatment or be pregnant compared with untreated women. Women using IVF or OI were as likely to have ectopic pregnancies, stillbirths, or premature or low birthweight babies as untreated women. Conclusion(s) More than 40% of women aged 28–36 years reporting a history of infertility can achieve births without using treatment, indicating they are subfertile rather than infertile.

Teaching Teachers for the Future (TTF) project TPACK Survey : summary of the key findings

This paper presents a summary of the key findings of the TTF TPACK Survey developed and administered for the Teaching the Teachers for the Future (TTF) Project implemented in 2011. The TTF Project, funded by an Australian Government ICT Innovation Fund grant, involved all 39 Australian Higher Education Institutions which provide initial teacher education. TTF data collections were undertaken at the end of Semester 1 (T1) and at the end of Semester 2 (T2) in 2011. A total of 12881 participants completed the first survey (T1) and 5809 participants completed the second survey (T2). Groups of like-named items from the T1 survey were subject to a battery of complementary data analysis techniques. The psychometric properties of the four scales: Confidence - teacher items; Usefulness - teacher items; Confidence - student items; Usefulness- student items, were confirmed both at T1 and T2. Among the key findings summarised, at the national level, the scale: Confidence to use ICT as a teacher showed measurable growth across the whole scale from T1 to T2, and the scale: Confidence to facilitate student use of ICT also showed measurable growth across the whole scale from T1 to T2. Additional key TTF TPACK Survey findings are summarised.

GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.