Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.

Delay of gratification: a comparison study of children with Down syndrome, moderate intellectual disability and typical development.

BACKGROUND: Self-regulation has been found to be an important contributor to a range of outcomes, with delay of gratification (a self-regulatory skill) predicting better academic, social and personal functioning. There is some evidence that individuals with Down syndrome have difficulty with delay of gratification. We investigated the question of whether this difficulty is common to intellectual disability irrespective of aetiology, or whether it presents a particular problem for those with Down syndrome. The latter was considered a possibility because of language difficulties in this group. METHOD: Three groups of children with a mean MA between 36 and 60 months participated in the study: children with Down syndrome (n = 32), children with a moderate intellectual disability from a cause other than Down syndrome (n = 26) and typically developing children (n = 50). Children completed a series of measures of language and cognitive functioning and participated in a delay of gratification task. RESULTS: The group of children with Down syndrome delayed for a significantly shorter time than either of the other two groups that did not differ from each other. Receptive language was associated with delay time for the children with Down syndrome but not for the typically developing group, nor for the group with moderate intellectual disability. CONCLUSIONS: Children with Down syndrome appear to have a particular difficulty with delay of gratification. Language abilities would seem to be implicated in this difficulty, although further examination of this hypothesis is required.

Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia.

PURPOSE: Muscarinic receptors are known to regulate several important physiologic processes in the eye. Antagonists to these receptors such as atropine and pirenzepine are effective at stopping the excessive ocular growth that results in myopia. However, their site of action is unknown. This study details ocular muscarinic subtype expression within a well documented model of eye growth and investigates their expression during early stages of myopia induction. METHODS: Total RNA was isolated from tree shrew corneal, iris/ciliary body, retinal, choroidal, and scleral tissue samples and was reverse transcribed. Using tree shrew-specific primers to the five muscarinic acetylcholine receptor subtypes (CHRM1-CHRM5), products were amplified using polymerase chain reaction (PCR) and their identity confirmed using automated sequencing. The expression of the receptor proteins (M1-M5) were also explored in the retina, choroid, and sclera using immunohistochemistry. Myopia was induced in the tree shrew for one or five days using monocular deprivation of pattern vision, and the expression of the receptor subtypes was assessed in the retina, choroid, and sclera using real-time PCR. RESULTS: All five muscarinic receptor subtypes were expressed in the iris/ciliary body, retina, choroid, and sclera while gene products corresponding to CHRM1, CHRM3, CHRM4, and CHRM5 were present in the corneal samples. The gene expression data were confirmed by immunohistochemistry with the M1-M5 proteins detected in the retina, choroid, and sclera. After one or five days of myopia development, muscarinic receptor gene expression remained unaltered in the retinal, choroidal, and scleral tissue samples. CONCLUSIONS: This study provides a comprehensive profile of muscarinic receptor gene and protein expression in tree shrew ocular tissues with all receptor subtypes found in tissues implicated in the control of eye growth. Despite the efficacy of muscarinic antagonists at inhibiting myopia development, the genes of the muscarinic receptor subtypes are neither regulated early in myopia (before measurable axial elongation) nor after significant structural change.

Binding of dexamethasone by alpha-crystallin.

PURPOSE: Long-term steroid therapy is a known risk factor for the development of posterior subcapsular cataract. Previous work in this laboratory has found soluble lens proteins to bind dexamethasone, but this binding is not due to a glucocorticoid receptor. This study was undertaken to identify the soluble protein or proteins involved in lens glucocorticoid binding. METHODS: Bovine lens extract was incubated with 5.2 x 10(-)(8) M [(3)H]-dexamethasone for 3 hours, and the distribution of label assessed in the soluble and insoluble fractions after centrifugation. Soluble lens extract was fractionated using gel permeation chromatography to isolate and identify proteins involved in the binding. Total lens proteins, high-molecular-weight proteins, or alpha-crystallin were exposed to dexamethasone and the protein bound steroid measured after separation of free and bound ligand on a gel chromatography column. Scatchard analysis was used to determine dexamethasone-binding parameters. Sequence comparisons between bovine alphaA- and alphaB-crystallins and glucocorticoid-binding proteins were performed using a sequence-alignment program. RESULTS: Of the total dexamethasone bound in lens extract, soluble proteins were found to account for 52%. The majority of the soluble protein-bound dexamethasone coeluted with the high-molecular-weight proteins that consisted mainly of alpha-crystallin. Binding studies with isolated proteins showed that alpha-crystallin accounted for more than 98% of total soluble dexamethasone binding in the lens. Scatchard analysis of steroid binding showed it to be a nonspecific partitioning event. Sequence comparisons between alphaA- and alphaB-crystallins and various glucocorticoid-binding proteins showed the lens proteins to have three regions of sequence homology with yeast corticosteroid-binding protein. CONCLUSIONS: alpha-Crystallin is the principal soluble glucocorticoid binding protein in the lens. The steroid association is described by nonspecific partitioning and may be related to the unique structural characteristics of the protein. The nonspecific association with alpha-crystallin is not thought to be functional; however, it may aid in the increased covalent steroid modification observed for this protein.

The preparation of reach to grasp movements in adults with Down syndrome.

The aim of this study was to determine the extent to which adults with Down syndrome (DS) are able to utilise advance information to prepare reach to grasp movements. The study comprised ten adults with DS; ten children matched to an individual in the group with DS on the basis of their intellectual ability, and twelve adult controls. The participants used their right hand to reach out and grasp illuminated perspex blocks. Four target blocks were positioned on a table surface, two to each side of the midsagittal plane. In the complete precue condition, participants were provided with information specifying the location of the target. In the partial precue condition, participants were given advance information indicating the location of the object relative to the midsagittal plane (left or right). In the null condition, advance information concerning the position of the target object was entirely ambiguous. It was found that both reaction times and movement times were greater for the participants with DS than for the adults without DS. The reaction times exhibited by individuals with DS in the complete precue condition were lower than those observed in the null condition, indicating that they had utilised advance information to prepare their movements. In the group with DS, when advance information specified only the location of the target object relative to the midline, reaction times were equivalent to those obtained when ambiguous information was given. In contrast, the adults without DS exhibited reaction times that were lower in both the complete and partial precue conditions when compared to the null condition. The pattern of results exhibited by the children was similar to that of the adults without DS. The movement times exhibited by all groups were not influenced by the precue condition. In summary, our findings indicate that individuals with DS are able to use advance information if it specifies precisely the location of the target object in order to prepare a reach to grasp movement. The group with DS were unable, however, to obtain the normal advantage of advance information specifying only one dimension of the movement goal (i.e., the position of an object relative to the body midline).

Metabolic rate: a factor in developing obesity in children with Down syndrome?

Resting metabolic rate and its relation with selected anthropometric measures was determined in 11 male and 7 female noninstitutionalized children with Down syndrome. Dietary analysis was performed to determine the nutritional status of the children and whether poor nutritional habits may be influencing factors in the development of obesity in this population. Resting metabolic rate for the total group was 170.4 +/- 38.65 ml.min-1 (0.17 +/- 0.04 ml.kg-1.min-1). Body weight, height, and surface area were moderately correlated with this rate, with height having the strongest relation. Daily caloric intake was 1,433.84 +/- 255.2 calories, comprising of 16.01 +/- 2.20% protein, 42.18 +/- 7.40% fat, and 40.60 +/- 8.83 carbohydrate. Calcium, potassium, and vitamin C were above and iron and thiamine below the recommended daily allowance.

Genetic screening for progressive retinal atrophy in the Australian population of Irish Setters.

OBJECTIVE: To determine whether the rcd-1 mutation causing progressive retinal atrophy (PRA) in Irish Setters is in the Australian breeding population. METHOD: DNA samples were tested for the mutation using the Polymerase Chain Reaction and specific primer nucleotides to amplify the phosphodiesterase gene followed by restriction enzyme cleavage and fragment size determination. RESULTS: No mutant alleles were found in 38 Irish Setters, representing over 80% of all major breeding stock in five Australian states. CONCLUSIONS: It is likely that the Australian population of Irish Setters is free of the rcd-1 form of PRA.

The frequency of the canine leukocyte adhesion deficiency (CLAD) allele within the Irish Setter population of Australia.

OBJECTIVE: To determine the frequency of the 107G-->C canine leukocyte adhesion deficiency (CLAD) mutation in Irish Setters from the Australian breeding population. METHOD: Genomic DNA was isolated from 87 Irish Setter blood samples and a region of the beta-2 integrin gene (ITGB2), encompassing the mutation, was amplified using real-time Polymerase Chain Reaction (PCR). Two fluorescently labelled probes were hybridised to the fragment, and fluorescence resonance energy transfer (FRET) was used to detect the 107G-->C mutation responsible for CLAD. RESULTS: Three new heterozygotes were identified among 87 healthy Irish Setters from Australia. All originated from a litter sired by a known heterozygote. A total of seven heterozygotes have now been identified in 92 dogs (7.6%), representing over 90% of all major breeding stock in five Australian states. Two of the heterozygotes were recently imported adult dogs and the others were their offspring. CONCLUSIONS: The frequency of the 107C allele in the Australian population of Irish Setters is lower than that in Europe. Selective breeding programs should be adopted to eliminate the mutant allele presently in two breeding lines.

Life be in it: lifestyle choices for active leisure.

For members of the community, participation in leisure, sports and recreation is an important lifestyle choice. Individuals with Down syndrome live in our community and they, too, are equally entitled to active lifestyle choices. Children, adolescents and adults with Down syndrome have a wide range of interests and, although reported trends indicate that their engagement in recreational activity is often sedentary and solitary in nature, other factors apart from the syndrome may account for this. Using a perception of difference perspective, this paper will examine certain aspects of their motor development, health and interactions with others which could be viewed as restrictive factors to their ability to participate in active leisure opportunities in the community. Program examples from Australia will be used to illustrate how a perception of difference which facilitates ability rather than disability across community based activities can enable a range of active leisure choices.

Delay of gratification in young adults with Down syndrome.

Thirty-one young adults (17-23 years of age) with Down syndrome participated in two self-imposed delay of gratification trials. Thirty-six and forty-eight percent waited for the experimenter to return (15 minutes) on Trials 1 and 2 respectively, and thirty-six percent waited for the experimenter on both occasions. Expressive language differentiated those who waited from those who did not. A discriminant analysis which included measures of expressive language, temperament characteristics and parental attitudes to childrearing gave very good separation of the two groups. Directions for future researched are discussed.

Glutamate uptake in retinal glial cells during diabetes.

AIMS: Glutamate recycling is a major function of retinal Muller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. METHODS: Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D: -aspartate, into Muller cells. RESULTS: There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D: -aspartate immunoreactivity was significantly increased in Muller cells of diabetic rats compared to controls (p<0.001). The EC(50) was found to increase by 0.304 log units in diabetic Muller cells compared with controls, suggesting that glutamate uptake is twice as efficient. CONCLUSIONS: These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Muller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.

Beyond sex and cooking: health education for individuals with intellectual disability.

Issues of health education programming for people with intellectual disability are discussed. As environments in which such individuals live become more inclusive, and they are encouraged to make their own choices, the issue of whether current health education is sufficient to enable them to make healthy life choices is considered. More attention should be focused on programs in schools and the community to fulfill this need. Three aspects of health education programming are considered: physical activity, general health knowledge, and social supports for health. Continuity of information is viewed as important in policy development as well as in interprofessional coordination and cooperation to assure that these individuals are not further handicapped by poor health.

Is there a glucocorticoid receptor in the bovine lens?

Prolonged glucocorticoid therapy is a risk factor for cataract development. The mechanism remains unknown. If cataract results from the direct effect of steroids on lens function, a glucocorticoid receptor is required. In order to determine whether such a receptor was present in the bovine lens, metabolic and steroid binding experiments were undertaken. Cultured bovine lens epithelial cells were exposed to 10(- 4)and 10(-8) M dexamethasone or prednisolone and the uptake and incorporation of(14)C leucine,(14)C glucose and(3)H thymidine, examined. Neither glucocorticoid affected cell protein synthesis or glucose uptake. Both dexamethasone concentrations and the lower concentration of prednisolone had no effect on thymidine uptake or incorporation, however, the 10(-4) M prednisolone exposure reduced these by 15 +/- 5%. This regulation is thought to be due to membrane fluidity changes and not the action of the glucocorticoid receptor. As the glucocorticoid receptor is very heat labile in vitro, the effects of increasing temperature on dexamethasone binding by proteins from lens epithelium, lens nucleus and liver were examined. At 0 degree C, lens epithelial extract bound nine-fold more dexamethasone than liver extract. After exposure to 37 degrees C, liver binding decreased by 66% whereas that for lens epithelium increased by 18%. For both lens extracts, steroid binding increased with temperature up to 50 degrees C. Scatchard analysis of the steroid binding kinetics showed there to be no high affinity sites in lens epithelial extract, with the binding best described as a non-specific partitioning event. Western blotting with a specific glucocorticoid receptor antibody revealed protein bands of approximately 94 and 79 kDa in liver, which is known to contain significant levels of receptor. No immunoreactivity was observed for lens epithelial extract. Therefore, within the limits of detection, these results suggest the bovine lens does not contain a glucocorticoid receptor. This raises questions about the validity of receptor-mediated mechanisms proposed for cataract development.

Deletion of 8p: a report of a child with normal intelligence.

The case is presented of a female infant with a distal deletion of 8p (8p23.1-->pter) whose development was monitored over a 5-year period from 12 months of age. Although previous literature has suggested that 8p deletion is associated with mild to moderate intellectual disability, the child reported here has normal intelligence. Despite initial delays in gross motor and language skills, cognitive development (assessed with the Bayley Scales of Infant Development) and intellectual ability (measured on the Stanford-Binet Intelligence Scale) were within average range. It is argued that the small number of previous case reports may have created a misleading impression of intellectual development in individuals with distal deletions of 8p.