Adverse Drug Reactions in Breastfed Infants: A Cross-Sectional Study of Lactating Mothers.

Background: Breastfeeding-related adverse drug reactions (ADRs) are thought to be uncommon as reported cases are globally low. The nonspecific nature of these reactions and a lack of awareness and difficulty in identification of ADRs by mothers and clinicians may result in these ADRs being underreported. Aims: This study hypothesized that breastfeeding-related infant ADRs are more frequent than reported. As a first-hand account of breastfeeding mothers, this study aimed to evaluate the impact of the perceived ADRs on the continuation of breastfeeding and maternal treatment. Methods: Women currently breastfeeding or having breastfed in the last 12 months were invited to complete an online survey. The survey comprised 42 questions in 5 sections to obtain data from breastfeeding mothers, including their use of medicines during lactation, perceptions of infant adverse reactions attributable to maternal medication use and its potential impact on breastfeeding. Results: This online survey was completed by 339 women, 42% of whom reported taking at least one medication during breastfeeding. ADRs were reported in 23 infants where a possible or probable causal relationship indicated by a Naranjo score of 1-8 was established in 16 (11.3%). Antibiotics (n = 12) and opioids (n = 2), including tramadol and oxycodone were identified as the most common adverse reaction-causing drugs. The average age of infants at the time of the perceived ADR was 25.6 days (95% confidence interval; 4-85 days; median age 17.5 days). Conclusion: Suspected ADR reporting in this study was significantly greater than those reported to the regulatory body, the Australian Therapeutics Goods Administration, which shows that common breastfeeding-related infant ADRs are underreported.

Are active efflux transporters contributing to infant drug exposure via breastmilk? A longitudinal study.

Although most drugs are considered safe and compatible with breastfeeding, cases of toxic drug exposure have been reported. Active efflux transporters have been implicated as a mechanism in the transfer of drugs from mother to baby via breastmilk. Using breastmilk as a source of human mammary epithelial cells, this novel longitudinal study investigated the expression of four active transporters, namely, MDR1, MRP1, MRP2 and BCRP in the lactating human breast. BCRP gene was found to be strongly overexpressed with levels peaking at 5 months postpartum, potentially indicating a time where a breastfed infant may be at risk of inadvertent exposure to BCRP substrates. Serum albumin, a major component of human breastmilk was increasingly downregulated as lactation progresses. Xanthine oxidase/dehydrogenase, an enzyme in breastmilk attributed to a reduced risk of gastroenteritis caused by Escherichia coli and Salmonella enteritides, was downregulated. Lysozyme and fatty acid synthase are progressively upregulated. This study also shows that breastmilk-derived epithelial cells, when propagated in culture, exhibit characteristics significantly different to those derived directly from breastmilk. This serves to warn that in vitro studies are not a true representation of in vivo processes in the lactating breast; hence, application of in vitro data should be conducted with caution.

Structured tool to improve clinical outcomes of type 2 diabetes mellitus patients: A randomized controlled trial.

BACKGROUND: Reviewing pharmacist diabetes intervention studies revealed a lack of structured process in providing diabetes care, leading to varied results from increased to minimal improvements. The aim of this study was to determine the effectiveness of the Simpler tool, a structured clinical guidelines tool, in the delivery of diabetes care. The primary outcome was significant improvement in HbA1c. Secondary outcomes were improved lipid profiles and blood pressure (BP). METHODS: A 6-month parallel multicenter two-arm, single-blind randomized controlled trial involving 14 pharmacists at seven primary care clinics was conducted in Johor, Malaysia. Pharmacists without prior specialized diabetes training were trained to use the tool. Patients were randomized within each center to either Simpler care (SC), receiving care from pharmacists who used the tool (n =55), or usual care (UC), receiving usual care and dispensing services (n = 69). RESULTS: Compared with UC, SC significantly reduced HbA1c (mean reduction 1.59% [95% confidence interval {CI} -2.2, -0.9] vs 0.25% [95% CI -0.62, 0.11], respectively; P ≤ 0.001), and significantly improved systolic BP (-6.28 mmHg [95% CI -10.5, 2.0] vs 0.26 mmHg [95% CI -3.74, 0.43], respectively; P = 0.005). A significantly higher proportion of patients in the SC than UC arm reached the Malaysian guideline treatment goals for HbA1c (14.3% vs 1.5%; P = 0.020), systolic BP (80% vs 42%; P = 0.001), and low-density lipoprotein cholesterol (60.5% vs 40.4%; P = 0.046). CONCLUSIONS: Using the Simpler tool facilitated the delivery of comprehensive evidence-based diabetes management and significantly improved clinical outcomes. The Simpler tool supported pharmacists in providing enhanced structured diabetes care.

The use of non-prescription medicines during lactation: A qualitative study of community pharmacists' attitudes and perspectives.

BACKGROUND: Community pharmacists play a significant role in the provision of non-prescription medicines. There is evidence that women self-medicate and use non-prescription medicines whilst breastfeeding. Studies have demonstrated that breastfeeding women are likely to seek advice from pharmacists, presenting a unique opportunity for pharmacists to provide on-going support of these women especially in relation to the appropriate use of non-prescription medicines. OBJECTIVES: This study aimed to explore community pharmacists' attitudes and perspectives towards the use of non-prescription medicines during breastfeeding. METHODS: This exploratory study was conducted through semi-structured interviews with 30 community pharmacists in Western Australia, between July and September 2013. Transcribed data were analysed using descriptive and qualitative approaches. NVivo® Version 10.0 was used to organise qualitative data and quotations to facilitate thematic analysis. RESULTS: Four major themes emerged. Despite the positive attitudes and favourable perceived knowledge level, participants often found themselves in a dilemma when required to make clinical recommendations especially in situations where there was a therapeutic need for treatment but clear guidelines or evidence to suggest safety of the medicines or treatment in lactation was absent. Despite the popularity of complementary medicines, participants felt more confident in providing advice in relation to conventional over complementary medicines. Whilst medication safety is within the field of expertise of pharmacists, the absence of information and safety data was seen as a major challenge and barrier to enable pharmacists to confidently provide evidence-based recommendations. CONCLUSIONS: This study has enhanced our understanding of the attitudes and perspectives of community pharmacists towards the use of non-prescription, including complementary medicines, during breastfeeding. Future studies are warranted to confirm the safety of commonly used or requested medicines in breastfeeding. University training and continuing education for pharmacists should include the latest information available regarding the use of both conventional and complementary medicines throughout lactation.

Consensus Validation of Simpler™: A Tool to Improve Pharmacist Delivery of Quality, Evidence-Based Diabetes Care.

BACKGROUND: Studies on a structured method used by pharmacists to provide comprehensive, evidence-based diabetes care are lacking. The aim of this study was to prioritise, rank and construct validate indicators categorised as seven treatment factors utilised in the management of type 2 diabetes namely: Cholesterol, blood pressure and glycaemia control; medication and lifestyle management; cardiovascular risk management and patient education using the Delphi process. METHODS: A Delphi questionnaire consisted of 29 Part 1 and nine Part 2 indicators which were incorporated into a tool called Simpler™. The indicators were mainly sourced from American, Australian and Malaysian diabetes management guidelines. Diabetes experts were asked to rank indicators in the order of importance in Part 1. In Part 2, indicators had to be chosen for inclusion into Simpler™ using a fivepoint Likert scale. The consensus level was pre-set at 60%. RESULTS: A three round Delphi process was used to validate all 38 indicators by 12 experts from Australia and Malaysia: five pharmacists, four doctors, two endocrinologists and a diabetes nurse. Consensus was reached for 93.1% (27/29) of the Part 1 indicators and all nine Part 2 indicators (100%). Five out of nine indicators in Part 2 questionnaire obtained consensus disagreement for inclusion into the Simpler ™ tool. CONCLUSION: The Simpler™ tool is the first structured diabetes multifactorial tool to address all seven evidence-based factors. The tool was refined and validated by multi-disciplinary health professionals from Australia and Malaysia. Pharmacists can use the Simpler™ tool to facilitate evidence-based comprehensive individualised care among type 2 diabetes patients.

Towards the implementation of breastfeeding-related health services in community pharmacies: Pharmacists' perspectives.

BACKGROUND: The scope of community pharmacy practice has expanded over the years. Pharmacists are now involved in the provision of a range of professional services. Pharmacists have regular contact with breastfeeding women, and are perceived as easily accessible, trusted health advisors. There is limited information on factors needed to be considered when implementing breastfeeding-related services in pharmacies to meet the needs of this population group. OBJECTIVE: This study aimed to explore community pharmacists' perspectives on the implementation of breastfeeding-related services, the factors to consider and the required implementation strategies in community pharmacies. METHODS: The study involved semi-structured interviews with 30 community pharmacists practising in Western Australian. Interviews were audio-recorded and transcribed verbatim to facilitate analysis. NVivo® Version 10.0 was used to aid organisation of qualitative data and thematic analysis. Responses to closed-ended questions were summarised using the descriptive approach. RESULTS: Participants' perceptions about their role in providing breastfeeding-related services in community pharmacies were generally favourable. Participants reported receiving regular enquiries from the public about the use of various medicines during breastfeeding, in particular non-prescription medicines. Most of their knowledge regarding the use of medicines in breastfeeding and breastfeeding in general was a culmination of day-to-day work experience, self-directed continuing professional development, personal or close-contact breastfeeding experience, and university training. Multifaceted efforts including public and professional education, research and development, and government initiatives were identified as essential to facilitate quality use of medicines in breastfeeding, and to increase pharmacists' support of breastfeeding women. CONCLUSION: Based on the needs and demand, appropriate training and continuing development is warranted so that pharmacists are well-equipped with knowledge regarding the use of medicines in breastfeeding, and breastfeeding in general. There appear to be opportunities for pharmacists to expand their professional services and contribute towards improved care and support of breastfeeding women at primary care level.

A Narrative Review of Diabetes Intervention Studies to Explore Diabetes Care Opportunities for Pharmacists.

Background. We conducted a review of current diabetes intervention studies in type 2 diabetes and identified opportunities for pharmacists to deliver quality diabetes care. Methods. A search on randomised controlled trials (RCT) on diabetes management by healthcare professionals including pharmacists published between 2010 and 2015 was conducted. Results and Discussion. Diabetes management includes multifactorial intervention which includes seven factors as outlined in diabetes guidelines, namely, glycaemic, cholesterol and blood pressure control, medication, lifestyle, education, and cardiovascular risk factors. Most studies do not provide evidence that the intervention methods used included all seven factors with exception of three RCT which indicated HbA1c (glycated hemoglobin) reduction range of 0.5% to 1.8%. The varied HbA1C reduction suggests a lack of standardised and consistent approach to diabetes care. Furthermore, the duration of most studies was from one month to two years; therefore long term outcomes could not be established. Conclusion. Although pharmacists' contribution towards improving clinical outcomes of diabetes patients was well documented, the methods used to deliver structured, consistent evidence-based care were not clearly stipulated. Therefore, approaches to achieving long term continuity of care are uncertain. An intervention strategy that encompass all seven evidence-based factors will be useful.

The Use, Perceived Effectiveness and Safety of Herbal Galactagogues During Breastfeeding: A Qualitative Study.

The World Health Organization recommends breastfeeding as the normal infant feeding method and that infants being breastfed should be regarded as the control group or norm reference in all instances. There are many factors which could contribute to a new mother ceasing breastfeeding early, with the most commonly reported reason being perceived insufficient breast milk supply. The use of herbal galactagogues is increasingly common worldwide. Literature review identified a need for more research in the area of herbal galactagogue use during breastfeeding. Twenty in-depth semi-structured interviews were undertaken with breastfeeding women who used herbal galactagogues, to document use and explore their perceived effectiveness and safety of herbal galactagogues. Several indicators of breastfeeding adequacy were mentioned as participants described their experiences with the use of herbal galactagogues. Confidence and self-empowerment emerged as an over-arching theme linked to positive experiences with the use of herbal galactagogues. Despite the lack of clinical trial data on the actual increase in measured volume of breast milk production, indicators of breastfeeding adequacy boosted participants' confidence levels and resulted in psychological benefits. This study highlighted the importance of considering the potential psychological benefits of using herbal galactagogues, and how this translates into breastfeeding adequacy.

What Do Breastfeeding Women Taking Herbal Galactagogues Perceive of Community Pharmacists' Role in Breastfeeding Support? A Qualitative Study.

Information from pharmacists may affect breastfeeding womens' decisions and choice of therapy. Community pharmacies remain one of the main sources of herbal medicines in Australia. In this study, we aimed to explore the perspectives of breastfeeding women on pharmacists' role and whether there is potential for role expansion, as well as the facilitators and barriers in meeting their healthcare-related needs in the community pharmacy setting. Semi-structured in-depth interviews were conducted with 20 Western Australian women who were using one or more herbal galactagogues while breastfeeding. Participants' views were classified into three major themes: (i) facilitators and (ii) barriers to an increased role of pharmacists; and (iii) implementation of breastfeeding related-services in community pharmacy settings. Overall perspectives of participants were positive about the potential for role expansion of pharmacists to meet their breastfeeding-related needs. Whilst most participants perceived community pharmacies as convenient sources of trusted information, some recognised barriers to an increased role of pharmacists. Several breastfeeding support services perceived to be useful in community pharmacy settings were identified. Issues raised highlighted areas of pharmacy practice which required improvement and revealed opportunities for expansion of pharmacists' role to better support women and promote breastfeeding in the community.

Perspectives and attitudes of breastfeeding women using herbal galactagogues during breastfeeding: a qualitative study.

BACKGROUND: Some herbal galactagogues have gained reputation and recognition by the public and health professionals as alternative approaches to increase breast milk supply. This study explores the perspectives and attitudes of breastfeeding women towards the use of herbal galactagogues while breastfeeding, their experiences, and why and how they have chosen an alternative option over conventional treatments to enhance breastfeeding performance. METHODS: This exploratory research was conducted through in-depth semi-structured interviews with women living in Perth, Western Australia, who were using one or more herbal galactagogues during breastfeeding. Purposeful and subsequent snowball sampling methods were employed to recruit participants. All interviews, facilitated by an interview guide, were audio-recorded, then transcribed verbatim. Thematic analysis was used to analyse qualitative data to construct themes and subthemes. RESULTS: The perspectives and attitudes of the 20 participants are classified under three main headings: i) use of herbal medicines during breastfeeding, ii) available herbal medicines resources, and iii) level of breastfeeding support received. Throughout the interviews, participants described how their perseverance and determination to breastfeed, as well as concerns over breastfed infants' safety with conventional treatments, influenced their choice of therapy. A sense of self-efficacy and autonomy over their own health needs was seen as influential to their confidence level, supported self-empowerment and provided reassurance throughout the breastfeeding journey. There was also a desire for more evidence-based information and expectations of health professionals to provide credible and reliable information regarding the use of herbal medicines during breastfeeding. CONCLUSIONS: This study has enhanced our understanding of the perspectives and attitudes of breastfeeding women towards the use of herbal medicines, in particular galactagogues, while breastfeeding. The positive attitudes of breastfeeding women identified in this study highlight the need for further research into evaluating the safety and efficacy of commonly used herbal galactagogues, whilst the negative views on breastfeeding education should be taken into consideration when implementing or improving breastfeeding-related health policies.

The use of herbal medicines during breastfeeding: a population-based survey in Western Australia.

BACKGROUND: Main concerns for lactating women about medications include the safety of their breastfed infants and the potential effects of medication on quantity and quality of breast milk. While medicine treatments include conventional and complementary medicines, most studies to date have focused on evaluating the safety aspect of conventional medicines. Despite increasing popularity of herbal medicines, there are currently limited data available on the pattern of use and safety of these medicines during breastfeeding. This study aimed to identify the pattern of use of herbal medicines during breastfeeding in Perth, Western Australia, and to identify aspects which require further clinical research. METHODS: This study was conducted using a self-administered questionnaire validated through two pilot studies. Participants were 18 years or older, breastfeeding or had breastfed in the past 12 months. Participants were recruited from various community and health centres, and through advertising in newspapers. Simple descriptive statistics were used to summarise the demographic profile and attitudes of respondents, using the SPSS statistical software. RESULTS: A total of 304 questionnaires from eligible participants were returned (27.2% response rate) and analysed. Amongst the respondents, 59.9% took at least one herb for medicinal purposes during breastfeeding, whilst 24.3% reported the use of at least one herb to increase breast milk supply. Most commonly used herbs were fenugreek (18.4%), ginger (11.8%), dong quai (7.9%), chamomile (7.2%), garlic (6.6%) and blessed thistle (5.9%). The majority of participants (70.1%) believed that there was a lack of information resources, whilst 43.4% perceived herbal medicines to be safer than conventional medicines. Only 28.6% of users notified their doctor of their decision to use herbal medicine(s) during breastfeeding; 71.6% had previously refused or avoided conventional medicine treatments due to concerns regarding safety of their breastfed infants. CONCLUSIONS: The use of herbal medicines is common amongst breastfeeding women, while information supporting their safety and efficacy is lacking. This study has demonstrated the need for further research into commonly used herbal medicines. Evidence-based information should be available to breastfeeding women who wish to consider use of all medicines, including complementary medicines, to avoid unnecessary cessation of breastfeeding or compromising of pharmacotherapy.

rAAV.sFlt-1 gene therapy achieves lasting reversal of retinal neovascularization in the absence of a strong immune response to the viral vector.

PURPOSE: To determine the efficacy of rAAV.sFlt-1-mediated gene therapy in a transgenic mouse model of retinal neovascularization (trVEGF029) and to assess whether rAAV.sFlt-1 administration generated any deleterious, long-lasting immune response that could affect efficacy. METHODS: trVEGF029 mice were injected subretinally with rAAV.sFlt-1 or phosphate-buffered saline. Fluorescein angiography and electroretinography were used to compare the extent of fluorescein leakage from retinal vessels and retinal function, respectively. A group of eyes was enucleated, and the retinal vasculature and morphology were studied by confocal and light microscopy. Cells were isolated from the posterior eyecups and spleens of a further group, and immune cell subset populations were investigated by flow cytometry. sFlt-1 protein levels in the eyes were evaluated by ELISA. RESULTS: After a single rAAV.sFlt-1 injection, sFlt-1 protein levels were upregulated, and there was a reduction in fluorescein leakage from the retinal vessels and an improvement in retinal function. Confocal microscopy of isolectin-IB4-labeled retinal wholemounts showed more normal-appearing capillary beds in rAAV.sFlt-1-injected than in PBS-injected trVEGF029 mouse eyes. Light microscopy demonstrated retinal morphology preservation, with fewer aberrant vessels invading the outer nuclear layer of rAAV.sFlt-1-injected eyes. Furthermore, the immune response to subretinal injection of rAAV.sFlt-1 was limited to a transient increase in CD45(+) leukocytes that disappeared by 4 weeks after injection. This transient increase was localized to the eye and did not affect long-term therapeutic efficacy. CONCLUSIONS: The data support the notion that rAAV.sFlt-1 gene therapy is safe and effective for the long-term inhibition of deleterious blood vessel growth in the eye.

Regenerating optic axons restore topography after incomplete optic nerve injury.

Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons intact, restores normal topography. Strict RGC axon topography allowed us to preserve RGC axons on one side of the nerve (projecting to medial tectum) while lesioning those on the other side (projecting to lateral tectum). Topography and response properties for both RGC axon populations were assessed electrophysiologically. The majority of intact RGC axons retained appropriate topography in medial tectum and had normal, consistently brisk, reliable responses. Regenerate RGC axons fell into two classes: those that projected topographically to lateral tectum with responses that tended to habituate and those that lacked topography, responded weakly, and habituated rapidly. Axon tracing by localized retinal application of carbocyanine dyes supported the electrophysiological data. RGC soma counts were normal in both intact and axotomized RGC populations, contrasting with the 30% RGC loss after complete injury. Unlike incomplete optic nerve injury in mammals, where RGC axon regeneration fails and secondary cell death removes many intact RGC somata, lizards experience a "win-win" situation: intact RGC axons favorably influence the functional outcome for regenerating ones and RGCs do not succumb to either primary or secondary cell death.

Early vascular and neuronal changes in a VEGF transgenic mouse model of retinal neovascularization.

PURPOSE: To investigate early retinal changes in a vascular endothelial growth factor (VEGF) transgenic mouse (tr029VEGF; rhodopsin promoter) with long-term damage that mimics nonproliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (PDR). METHODS: Rhodopsin and VEGF expression was assessed up to postnatal day (P)28. Vascular and retinal changes were charted at P7 and P28 using sections and wholemounts stained with hematoxylin and eosin or isolectin IB4 Griffonia simplicifolia Samples were examined using light, fluorescence, and confocal microscopy. RESULTS: Rhodopsin was detected at P5 and reached mature levels by P15; VEGF protein expression was transient, peaking at P10 to P15. In wild-type (wt) mice at P7, vessels had formed in the nerve fiber/retinal ganglion cell layer and showed a centroperipheral maturational gradient; some capillaries had formed a second bed on the vitread side of the inner nuclear layer (INL). By P28, the retinal vasculature had three mature capillary beds, the third abutting the sclerad aspect of the INL. In tr029VEGF mice, capillary bed formation was accelerated compared with that in wt, with abnormal vessels extending to the sclerad side of the INL by P7 and abnormally penetrating the photoreceptors by P28. Compared with P7, vascular lesions were more numerous at P28 when capillary dropout was also evident. At both stages, retinal layers were thinned most where abnormal vessel growth was greatest. CONCLUSIONS: Concomitant damage to the vasculature and neural retina at early stages in tr029VEGF suggest that both tissues are affected, providing opportunities to examine early cellular events that lead to long-term disease.

Failure to restore vision after optic nerve regeneration in reptiles: interspecies variation in response to axotomy.

Optic nerve regeneration within the reptiles is variable. In a snake, Viper aspis, and the lizard Gallotia galloti, regeneration is slow, although some retinal ganglion cell (RGC) axons eventually reach the visual centers (Rio et al. [1989] Brain Res 479:151-156; Lang et al. [1998] Glia 23:61-74). By contrast, in a lizard, Ctenophorus ornatus, numerous RGC axons regenerate rapidly to the visual centers, but unless animals are stimulated visually, the regenerated projection lacks topography and animals remain blind via the experimental eye (Beazley et al. [2003] J. Neurotrauma 20:1263-1269). V. aspis, G. galloti, and C. ornatus belong respectively to the Serpentes, Lacertidae, and Agamidae within the Eureptilia, the major modern group of living reptiles comprising the Squamata (snakes, lizards, and geckos) and the Crocodyllia. Here we have extended the findings on Eureptilia to include two geckos (Gekkonidae), Cehyra variegata and Nephrurus stellatus. We also examined a turtle, Chelodina oblonga, the Testudines being the sole surviving representatives of the Parareptilia, the more ancient reptilian group. In all three species, visually elicited behavioral responses were absent throughout regeneration, a result supported electrophysiologically; axonal tracing revealed that only a small proportion of RGC axons crossed the lesion and none entered the contralateral optic tract. RGC axons failed to reach the chiasm in C. oblonga, and in G. variegata, and N. stellatus RGC axons entered the opposite optic nerve; a limited ipsilateral projection was seen in G. variegata. Our results support a heterogeneous response to axotomy within the reptiles, each of which is nevertheless dysfunctional.

Failure to form a stable topographic map during optic nerve regeneration: abnormal activity-dependent mechanisms.

Visually evoked responses in the optic tectum are mediated by glutamate receptors. During development, there is a switch from N-methyl-d-aspartate (NMDA)- to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated activity as the retinotectal map refines and visual function ensues. A similar pattern is seen in goldfish as the map refines during optic nerve regeneration. Here we examined glutamate receptors during optic nerve regeneration in the lizard, Ctenophorus ornatus, in which an imprecise retinotopic map forms transiently but degrades, leaving animals blind via the experimental eye. Receptor function was examined using NMDA and AMPA/kainate antagonists during in vitro tectal recording of visually evoked post-synaptic extracellular responses. Expression of NR1 (NMDA) and GluR2 (AMPA) receptor subtypes was examined immunohistochemically. In unoperated control animals, responses were robust and AMPA/kainate receptor-mediated. When the imprecise map was present, responses were difficult to evoke and insecure; periods of spontaneous activity as well as inactivity were also noted. Although AMPA/kainate-mediated activity persisted and GluR2 immunoreactivity increased transiently, NMDA receptor-mediated activity was also consistently detected and NR1 expression increased. In the long term, when the map had degraded, responses were readily evoked and predominantly AMPA/kainate receptor-mediated although some NMDA-mediated activity and NR1 expression remained. We suggest that the asynchronous activity reaching the optic tectum results in an inability to recapitulate the appropriate functional sequences of expression of NMDA and AMPA/kainate receptors necessary to refine the retinotectal map.

Development of visual projections follows an avian/mammalian-like sequence in the lizard Ctenophorus ornatus.

Development of primary visual projections was examined in a lizard Ctenophorus ornatus by anterograde and retrograde tracing with DiI and by GAP-43 immunohistochemistry. Visual pathway development was essentially similar to that in birds and mammals and thus differed from patterns in fish or amphibians. A number of features characterised the development as mammalian-like. Three phases occurred in rapid succession after laying: outgrowth (2-3 weeks, early), exuberance (4-5 weeks, intermediate), and retraction to the adult pattern (6-8 weeks, late) at about the time of hatching and eye opening. Furthermore, ipsilateral projections developed with only a slight lag relative to the contralateral ones. The dorsally located fovea could be identified from early stages. Optic axons formed transient exuberant projections to the ipsilateral optic tectum, to the opposite optic nerve, and to nonvisual regions. The pattern resembled that formed in the long term by regenerating optic axons in C. ornatus (Dunlop et al. [2000b] J. Comp. Neurol. 416:188-200), suggesting that axons recognise molecular signals associated with the initial exuberant innervation but not those associated with subsequent refinement.