Impact of the physical environment of psychiatric wards on the use of seclusion.

BACKGROUND: The physical environment is presumed to have an effect on aggression and also on the use of seclusion on psychiatric wards. Multicentre studies that include a broad variety of design features found on psychiatric wards and that control for patient, staff and general ward characteristics are scarce. AIMS: To explore the effect of design features on the risk of being secluded, the number of seclusion incidents and the time in seclusion, for patients admitted to locked wards for intensive psychiatric care. METHOD: Data on the building quality and safety of psychiatric as well as forensic wards (n = 199) were combined with data on the frequency and type of coercive measures per admission (n = 23 868 admissions of n = 14 834 patients) on these wards, over a 12-month period. We used non-linear principal components analysis (CATPCA) to reduce the observed design features into a smaller number of uncorrelated principal components. Two-level multilevel (logistic) regression analyses were used to explore the relationship with seclusion. Admission was the first level in the analyses and ward was the second level. RESULTS: Overall, 14 design features had a significant effect on the risk of being secluded during admission. The 'presence of an outdoor space', 'special safety measures' and a large 'number of patients in the building' increased the risk of being secluded. Design features such as more 'total private space per patient', a higher 'level of comfort' and greater 'visibility on the ward', decreased the risk of being secluded. CONCLUSIONS: A number of design features had an effect on the use of seclusion and restraint. The study highlighted the need for a greater focus on the impact of the physical environment on patients, as, along with other interventions, this can reduce the need for seclusion and restraint.

Polysaccharide films built by simultaneous or alternate spray: a rapid way to engineer biomaterial surfaces.

We investigated polysaccharide films obtained by simultaneous and alternate spraying of a chitosan (CHI) solution as polycation and hyaluronic acid (HA), alginate (ALG), and chondroitin sulfate (CS) solutions as polyanions. For simultaneous spraying, the film thickness increases linearly with the cumulative spraying time and passes through a maximum for polyanion/CHI molar charge ratios lying between 0.6 and 1.2. The size of polyanion/CHI complexes formed in solution was compared with the simultaneously sprayed film growth rate as a function of the polyanion/CHI molar charge ratio. A good correlation was found. This suggests the importance of polyanion/polycation complexation in the simultaneous spraying process. Depending on the system, the film topography is either liquid-like or granular. Film biocompatibility was evaluated using human gingival fibroblasts. A small or no difference is observed in cell viability and adhesion between the two deposition processes. The CHI/HA system appears to be the best for cell adhesion inducing the clustering of CD44, a cell surface HA receptor, at the membrane of cells. Simultaneous or alternate spraying of CHI/HA appears thus to be a convenient and fast procedure for biomaterial surface modifications.

Simultaneous spray coating of interacting species: general rules governing the poly(styrene sulfonate)/poly(allylamine) system.

Simultaneous spraying of two solutions of interacting species onto a substrate held vertically leads to the formation of nanometer-sized coatings. Here we investigate the simultaneous spraying of poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) solutions leading to the formation of a film composed of PSS/PAH complexes. The thickness of this film increases linearly with the cumulative spraying time. For a given spraying rate of PAH (respectively PSS), the growth rate of the film depends strongly upon the PSS/PAH ratio and passes through a maximum for a PSS/PAH ratio lying between 0.55 and 0.8. For a PSS/PAH ratio that is maintained constant, the growth speed of the film increases linearly with the spraying rate of polyelectrolyte of both solutions. Using X-ray photoelectron spectroscopy, we find that the film composition is almost independent of the PSS/PAH (spayed) ratio, with composition very close to 1:1 in PSS:PAH film. The 1:1 PSS:PAH composition is explained by the fact that the simultaneous spraying experiments are carried out with salt-free solutions; thus, electroneutrality in the film requires exact matching of the charges carried by the polyanions and the polycations. Zeta potential measurements reveal that, depending on whether the PSS/PAH spraying rate ratio lies below or above the optimal spraying rate ratio, the film acquires a positive or a negative excess charge. We also find that the overall film morphology, investigated by AFM, is independent of the spraying rate ratio and appears to be composed of nanometer-sized grains which are typically in the 100 nm range.

Modulation of Cellular Colonization of Porous Polyurethane Scaffolds via the Control of Pore Interconnection Size and Nanoscale Surface Modifications.

Full-scale cell penetration within porous scaffolds is required to obtain functional connective tissue components in tissue engineering applications. For this aim, we produced porous polyurethane structures with well-controlled pore and interconnection sizes. Although the influence of the pore size on cellular behavior is widely studied, we focused on the impact of the size of the interconnections on the colonization by NIH 3T3 fibroblasts and Wharton's jelly-derived mesenchymal stem cells (WJMSCs). To render the material hydrophilic and allow good material wettability, we treated the material either by plasma or by polydopamine (PDA) coating. We show that cells weakly adhere on these surfaces. Keeping the average pore diameter constant at 133 µm, we compare two structures, one with LARGE (52 µm) and one with SMALL (27 µm) interconnection diameters. DNA quantification and extracellular matrix (ECM) production reveal that larger interconnections is more suitable for cells to move across the scaffold and form a three-dimensional cellular network. We argue that LARGE interconnections favor cell communication between different pores, which then favors the production of the ECM. Moreover, PDA treatment shows a truly beneficial effect on fibroblast viability and on matrix production, whereas plasma treatment shows the same effect for WJMSCs. We, therefore, claim that both pore interconnection size and surface treatment play a significant role to improve the quality of integration of tissue engineering scaffolds.

Bioinspired Nanofeatured Substrates: Suitable Environment for Bone Regeneration.

Bone mimicking coatings provide a complex microenvironment in which material, through its inherent properties (such as nanostructure and composition), affects the commitment of stem cells into bone lineage and the production of bone tissue regulating factors required for bone healing and regeneration. Herein, a bioactive mineral/biopolymer composite made of calcium phosphate/chitosan and hyaluronic acid (CaP-CHI-HA) was elaborated using a versatile simultaneous spray coating of interacting species. The resulting CaP-CHI-HA coating was mainly constituted of bioactive, carbonated and crystalline hydroxyapatite with 277 ± 98 nm of roughness, 1 µm of thickness, and 2.3 ± 1 GPa of stiffness. After five days of culture, CaP-CHI-HA suggested a synergistic effect of intrinsic biophysical features and biopolymers on stem cell mechanobiology and nuclear organization, leading to the expression of an early osteoblast-like phenotype and the production of bone tissue regulating factors such as osteoprotegerin and vascular endothelial growth factor. More interestingly, amalgamation with biopolymers conferred to the mineral a bacterial antiadhesive property. These significant data shed light on the potential regenerative application of CaP-CHI-HA bioinspired coating in providing a suitable environment for stem cell bone regeneration and an ideal strategy to prevent implant-associated infections.

Step-by-step build-up of covalent poly(ethylene oxide) nanogel films.

Hydrogels based on poly(ethylene glycol) (PEG) are commonly used for studies related to cell fate and tissue engineering. Here we present a new covalent layer-by-layer build-up process leading to PEG coatings of nanometer size called "nanogel films". Compared to macroscopic hydrogels, such nanogels should provide a fine control over the structure and the thickness of the coating. Alternated deposition of bifunctional and tetra functional PEG molecules reacting through thiol/maleimide click chemistry is evaluated by quartz crystal microbalance. We first study parameters influencing the build-up process of such coatings and demonstrate the importance of (i) the nature of the first deposited layer, (ii) the PEG concentrations and (iii) the length of the PEG chains that appears to be the most significant parameter influencing film growth. The build-up process can be extended to a large variety of substrates like SiO2 or polymers by using an appropriate anchoring layer. Covalent functionalization of these nanogel films by proteins or enzymes is suited by modifying the biomolecules with thiol or maleimide groups and immobilizing them during the build-up process. Activity of the embedded enzymes can be maintained. Moreover ligands like biotin can be incorporated into the film and recognition by streptavidin can be modulated by playing with the number of PEG layers covering biotin. Compared to well-known PEG hydrogels, these new coatings are promising as they allow to (i) build thin nanometric coatings, (ii) finely control the amount of deposited PEG and (iii) organize the position of the embedded biomolecules inside the film layers.

Harnessing Wharton's jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors.

An important aim of bone regenerative medicine is to design biomaterials with controlled chemical and topographical features to guide stem cell fate towards osteoblasts without addition of specific osteogenic factors. Herein, we find that sprayed bioactive and biocompatible calcium phosphate substrates (CaP) with controlled topography induce, in a well-orchestrated manner, Wharton's jelly stem cells (WJ-SCs) differentiation into osteoblastic lineage without any osteogenic supplements. The resulting WJ-SCs commitment exhibits features of native bone, through the formation of three-dimensional bone-like nodule with osteocyte-like cells embedded into a mineralized type I collagen. To our knowledge, these results present the first observation of a whole differentiation process from stem cell to osteocytes-like on a synthetic material. This suggests a great potential of sprayed CaP and WJ-SCs in bone tissue engineering. These unique features may facilitate the transition from bench to bedside and the development of successful engineered bone. STATEMENT OF SIGNIFICANCE: Designing materials to direct stem cell fate has a relevant impact on stem cell biology and provides insights facilitating their clinical application in regenerative medicine. Inspired by natural bone compositions, a friendly automated spray-assisted system was used to build calcium phosphate substrate (CaP). Sprayed biomimetic solutions using mild conditions led to the formation of CaP with controlled physical properties, good bioactivity and biocompatibility. Herein, we show that via optimization of physical properties, CaP substrate induce osteogenic differentiation of Wharton's jelly stem cells (WJ-SCs) without adding osteogenic supplement factors. These results suggest a great potential of sprayed CaP and WJ-SCs in bone tissue engineering and may facilitate the transition from bench to beside and the development of clinically successful engineered bone.

Polyelectrolyte multilayer film coating and stability at the surfaces of oral prosthesis base polymers: an in vitro and in vivo study.

A new type of coating involving a layer-by-layer technique has been recently reported. This coating is composed of a polyelectrolyte multilayer film that confers specific properties on surfaces to which it is applied. Here, we studied the applicability of such a technique to the coating of oral prostheses, by first testing the construction of polyelectrolyte multilayer films on several polymers used in oral prosthesis bases, and, subsequently, by studying the stability of these coatings in vitro, in human saliva, and in vivo in a rat model. We demonstrated that the multilayered films are able to coat the surfaces of all tested polymers completely, thus increasing their wettability. We also showed that saliva does not degrade the film after 7 days in vitro and after 4 days in vivo. Taken together, our results establish that the layer-by-layer technique is suitable for the coating of oral devices.

Initial adhesion of endothelial cells on polyelectrolyte multilayer films.

Polyelectrolyte multilayer films were recently investigated to favour attachment of Human Vein Umbilical Endothelial Cells (HUVECs) on non-adhesive surfaces. In this study, we evaluated the initial adhesion of HUVECs after 3 h of seeding on two polyelectrolyte multilayer films ending by poly(D-lysine) (PDL) or poly(allylamine hydrochloride) (PAH). In order to obtain information about initial adhesion of HUVECs, cell morphology as well as the expression of beta1 integrins, specific receptors of adhesion, were evaluated after 3 h of seeding on polyelectrolyte multilayer films. The data were also compared to PDL or PAH monolayers (polyelectrolytes terminating the multilayer architecture). The expression of beta1 integrins was not different, whatever are the studied surfaces. However, HUVECs spreading on polyelectrolyte multilayer films, in particular on PAH ending film, was more important as compared to polyelectrolyte monolayers or glass. In conclusion, the best initial adhesion conditions of HUVECs on polyelectrolyte films could not be elucidated, moreover the results suggested also that beta1 integrins could only play a limited role.

Do physiological concentrations of IgG induce a direct aggregation of red blood cells: comparison with fibrinogen.

Under physiological conditions, red blood cells (RBCs) form aggregates that allow blood flow in all the circulatory system. RBC aggregation is the result of local flow shear stress, erythrocyte properties and macromolecular interactions between adjacent cells. Plasma proteins like fibrinogen or IgG are considered to promote RBC aggregation by a mechanism that remains to be explained. In the present study, we have examined the precise role of IgG on RBC fast-phase aggregation, in comparison with that of fibrinogen. Under our experimental conditions, we observed no fast-phase aggregating effect for IgG, at either physiological or supraphysiological concentrations, while fibrinogen induces strong aggregation of RBC. We also suspect the other plasma proteins to play a role in the RBC aggregating process.

Behaviour of endothelial cells seeded on thin polyelectrolyte multilayered films: a new biological scaffold.

The surface modification using thin polyelectrolyte multilayered films was proposed as a new scaffold material for different cell lines. In this study, we evaluated the possible use of polyelectrolyte multilayers as surface modification for the development of endothelial cells. In order to control the behaviour of endothelial cells, cell viability by MTT assay was studied. Moreover, the endothelial cell phenotype was checked and the expression of a leukocyte adhesion molecule (ICAM-1) was quantified. The behaviour of the cells on two polyelectrolyte multilayers was compared to cells on polystyrene, and two polyelectrolyte monolayers (terminating the multilayer architectures). The results have shown a better cell viability on the polyelectrolyte multilayers, inducing a higher cell number compared to polyelectrolyte monolayers after 1 and 3 days of culture. Moreover, the cells showed a normal morphology of cytoskeleton. The phenotype of the endothelial cells was kept and a low level of leukocyte adhesion molecules was observed. In conclusion, the polyelectrolyte multilayers can be considered as a potential surface modification procedure to enhance the development of endothelial cells on hydrophobic substrate and which can be applied to vascular tissue engineering.

Surface confined self-assembly of polyampholytes generated from charge-shifting polymers.

Polyampholyte-based films can be efficiently self-assembled onto a surface in a one-pot manner. By using a gradient of protons, morphogens, generated at an electrode surface, a charge-shifting polyelectrolyte present in solution can be transformed into a polyampholyte, leading to the continuous buildup of a film based on polyelectrolyte complexation.

Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women.

The current study was initiated to determine whether insulin resistance and/or hyperinsulinemia affected the ability of obese individuals to lose weight in response to hypocaloric diets. Thirty-one obese, nondiabetic women, with values for body mass index ranging from 28.0-35.0 kg/m2, volunteered for this program. Resistance to insulin-mediated glucose disposal was assessed by determining their steady state plasma insulin and glucose concentration during the last 30 min of a 180-min infusion of somatostatin, insulin, and glucose. The total integrated insulin response to breakfast and lunch was also determined. After the baseline measurements, volunteers were placed on a hypocaloric diet calculated to lead to a minimum weekly loss of 1% of ideal body weight. Individuals who met the criteria after 30 days of dieting were defined as weight loss successes (n = 20) and continued on the diet for another 30 days. Individuals not meeting the criteria were designated as weight loss failures (n = 12) and were discharged from the study. There was a mean (+/-SEM) weight loss at 60 days of 9.2 +/- 0.4 kg in the 20 individuals defined as weight loss successes, but there was no correlation between weight loss and either steady state plasma glucose or the total integrated insulin response (r < 0.1; P > 0.83). Furthermore, using the same criteria to define insulin sensitivity and insulin resistance as those for therapeutic successes, the therapeutic failures comprised six insulin-sensitive and five insulin-resistant subjects. In summary, insulin-mediated glucose disposal varied widely in nondiabetic, obese women, and there was no relationship between baseline insulin resistance or total integrated insulin response and weight loss. It is concluded that the ability to lose weight on a calorie-restricted diet over a short time period does not vary in obese, healthy women as a function of insulin resistance or hyperinsulinemia.

Can changes in plasma insulin concentration explain the variability in leptin response to weight loss in obese women with normal glucose tolerance?

The aim of this study was to test the hypothesis that the fall in circulating insulin concentration associated with moderate weight loss determines the associated decrease in plasma leptin concentration. For this purpose, 12 healthy, nondiabetic, obese women were studied before and after an average weight loss of 9.5 kg (11.2% of initial body weight). Plasma leptin concentrations fell from a mean (+/-SE) value of 35 +/- 3 to 17 +/- 2 ng/mL (P < 0.001) in association with the loss of weight. However, there was no correlation between the decline in leptin concentration and the associated fall in weight, body mass index, fat mass, or percent body fat. Furthermore, no correlation was seen among changes in fasting plasma glucose or insulin concentrations, the 8-h integrated plasma glucose response to breakfast and lunch, or the estimate of insulin-mediated glucose disposal. The only measured variable that correlated with the fall in plasma leptin concentration (r = 0.78; P < 0.005) was the decline in the 8-h integrated plasma insulin response after weight loss (from 304 +/- 44 to 232 +/- 36 microU/8 h x mL; P < 0.001). Finally, multivariate regression analysis, using various estimates of degree of obesity, insulin resistance, integrated glucose response, and integrated insulin response as dependent variables, indicated that only the insulin response was independently related to the decrease in leptin concentration (P = 0.035). The fall in integrated insulin response accounted for 66% of the variance in leptin concentrations after weight loss, and this was true no matter what the estimate of change in degree of obesity. In addition to offering an explanation for the variance in postweight loss leptin concentrations, these data provide further evidence of the importance of ambient insulin concentrations in the regulation of plasma leptin concentrations.

Postprandial triglyceride and retinyl ester responses to oral fat: effects of fructose.

It has been shown that addition of fructose to an oral fat load results in higher postprandial concentrations of triglyceride. The present study, performed in 11 healthy volunteers, was initiated to see whether the effect of fructose on fat-induced lipemia also involved changes in postprandial concentrations of triglyceride-rich lipoproteins of intestinal origin. Vitamin A was used to label intestinal lipoproteins, and the retinyl palmitate concentrations were determined in plasma and in the Sf > 400 and Sf 20-400 lipoprotein fractions (Sf denotes the Svedberg flotation index). Addition of fructose (50 g) to a standard (40-g oral) fat load resulted in higher postprandial concentrations of triglyceride and retinyl palmitate in plasma and the Sf > 400 lipoprotein fraction (P < 0.001, analysis of variance), and the higher the fasting plasma triglyceride concentration, the greater the magnitude of the fructose effect (r = 0.83, P < 0.002). These data show that triglyceride-rich lipoproteins of intestinal origin play a role in the fructose-induced accentuation of postprandial lipemia.

Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.

The effects of variations in dietary carbohydrate and fat on various aspects of carbohydrate and lipoprotein metabolism were evaluated in 10 healthy, postmenopausal women. The two diets were isoenergetic, assigned in random fashion, and consisted (as a % of total energy) of 15% protein, 60% carbohydrate, and 25% fat (60%-carbohydrate diet) or 15% protein, 40% carbohydrate, and 45% fat (40%-carbohydrate diet). Fasting plasma triacylglycerol, very-low-density-lipoprotein (VLDL) triacylglycerol, and VLDL-cholesterol concentrations were higher (P < 0.05-0.001) after the 60%-carbohydrate diet, whereas high-density-lipoprotein (HDL) cholesterol was lower (P < 0.05). Plasma insulin and triacylglycerol concentrations were also higher (P < 0.001) from 0800 to 0000 with the 60%-carbohydrate diet than with the 40%-carbohydrate diet. In addition, when vitamin A was given with the noon meal, the ensuing concentrations of retinyl palmitate were also higher after ingestion of the 60%-carbohydrate diet. Resistance to insulin-mediated glucose disposal, quantified at baseline by determining the steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of somatostatin, insulin, and glucose, correlated with the incremental increases in postprandial concentrations of plasma glucose (r = 0.68, P = 0.06), insulin (r = 0.82, P < 0.02), triacylglycerol (r = 0.77, P < 0.05), and retinyl palmitate (r = 0.68, P = 0.06) and with the Sf > 400 triacylglycerol (r = 0.77, P < 0.05), Sf 20-400 triacylglycerol (r = 0.72, P < 0.05), and Sf > 400 retinyl palmitate (r = 0.75, P < 0.01) lipoprotein fractions. Because all of these changes would increase risk of ischemic heart disease in postmenopausal women, it seems reasonable to question the wisdom of recommending that postmenopausal women consume low-fat, high-carbohydrate diets.

Polyelectrolyte multilayer films with pegylated polypeptides as a new type of anti-microbial protection for biomaterials.

Adhesion of bacteria at the surface of implanted materials is the first step in microbial infection, leading to post-surgical complications. In order to reduce this adhesion, we show that poly(L-lysine)/poly(L-glutamic acid) (PLL/PGA) multilayers ending by several PLL/PGA-g-PEG bilayers can be used, PGA-g-PEG corresponding to PGA grafted by poly(ethylene glycol). Streaming potential and quartz crystal microbalance-dissipation measurements were used to characterize the buildup of these films. The multilayer films terminated by PGA and PGA-g-PEG were found to adsorb an extremely small amount of serum proteins as compared to a bare silica surface but the PGA ending films do not reduce bacterial adhesion. On the other hand, the adhesion of Escherichia coli bacteria is reduced by 72% on films ending by one (PLL/PGA-g-PEG) bilayer and by 92% for films ending by three (PLL/PGA-g-PEG) bilayers compared to bare substrate. Thus, our results show the ability of PGA-g-PEG to be inserted into multilayer films and to drastically reduce both protein adsorption and bacterial adhesion. This kind of anti-adhesive films represents a new and very simple method to coat any type of biomaterials for protection against bacterial adhesion and therefore limiting its pathological consequences.

Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.

Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutraminine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. Weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant.

Development of the rabbit retina. V. The question of 'columnar units'.

A qualitative and quantitative description of the columnar units in the mammalian retina, and a discussion of their ontogeny and putative functions is given. Columnar arrangements of cells exist in the developing retina which can be observed by means of scanning electron microscopy. In the adult retina, each Müller cell ensheaths a columnar group of neuronal cells. Counting the number of cells in radial H/E stained sections at various developmental stages reveals a constant ratio of neuronal cells per Müller cell, independent of the developmental stage (after postnatal day 9), and independent of the retinal topography. Such groups of cells always consist of one Müller cell, 11 rod photoreceptor cells, about 2 bipolar cells, and 1 to 2 amacrine cells. Retinal ganglion cells, cone photoreceptor cells, and horizontal cells are more sparsely distributed in the retina than these units; since they are known to arise earlier in the ontogenesis than other cell types they are considered to exist independently of the columnar units. It is suggested that the units arise by migration of groups of preneurons along a common Müller (precursor) cell; these preneurons and the corresponding Müller cell may be clonally related. In the adult retina, such columns might constitute metabolic and functional units.

The structure of rabbit retinal Müller (glial) cells is adapted to the surrounding retinal layers.

Radial glial (Müller) cells of the rabbit retina were studied by various techniques including Golgi impregnation, scanning electron microscopy, horseradish peroxidase application, and staining of enzymatically isolated cells. This combination of methods produced detailed information on the specialized morphology of the Müller cells within the different topographical regions of the retina, and of the Müller cell processes within the various retinal layers. As a general rule, the retinal periphery contains short thick Müller cells with big endfeet, whereas the thick central retina is occupied by long slender cells with small endfeet. Independent of their location within the retina, Müller cell processes were found to be adapted to the structure of the surrounding retinal layers. Within the outer and inner nuclear layers, Müller cell processes (and somata) extend thin cytoplasmic "bubbles" ensheathing the neuronal somata, as do the "velate" astrocytes in the brain. In the plexiform layers, Müller cells extend many fine side branches between the neuropil, comparable to the protoplasmic astrocytes of the brain. In the thick myelinated nerve fibre layer of the central retina the Müller cell processes are rather smooth, similar to those of fibrous astrocytes. It is concluded that the neuronal microenvironment determines the morphology of a given glial process, or even of a part of a glial process running through a specialized neuronal compartment.