Inflammatory cells proliferate in the choroid and retina without choroidal thickness change in early Type 1 diabetes.

Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal inflammatory changes in diabetes have been reported and in vivo choroidal thickness (CT) has been searched as a marker of retinopathy with contradictory results. We aimed to investigate the early stages in the retina and choroid in an animal model of Type 1 diabetes. Type 1 diabetes was induced in male Wistar rats via a single i.p. streptozotocin injection. At 8 weeks after disease onset, CT, choroidal vascular density, VEGF and VEGFR2 expression, microglial cell and pericyte distribution were evaluated. Diabetic rats showed no significant change in CT and choroidal vascular density. A widened pericyte-free gap between the retinal pigment epithelium and the choroid was observed in diabetic rats. The immunoreactivity of VEGFR2 was decreased in the retina of diabetic rats, despite no statistically significant difference in the immunoreactivity of VEGF. The density of microglial cells significantly increased in the choroid and retina of diabetic rats. Reactive microglial cells were found to be more abundant in the choroid of diabetic rats. Evidences of the interconnection between the superficial, intermediate, and deep plexuses of the retina were also observed. At early stages, Type 1 diabetes does not affect choroidal thickness and choroidal vascular density. Proliferation and reactivity of microglial cells occurs in the choroidal stroma and the retina. The expression of VEGFR2 decreases in the retina.

Liraglutide Protects Against Brain Amyloid-ß1-42 Accumulation in Female Mice with Early Alzheimer's Disease-Like Pathology by Partially Rescuing Oxidative/Nitrosative Stress and Inflammation.

Alzheimer's disease (AD) is the most common form of dementia worldwide, being characterized by the deposition of senile plaques, neurofibrillary tangles (enriched in the amyloid beta (Aß) peptide and hyperphosphorylated tau (p-tau), respectively) and memory loss. Aging, type 2 diabetes (T2D) and female sex (especially after menopause) are risk factors for AD, but their crosslinking mechanisms remain unclear. Most clinical trials targeting AD neuropathology failed and it remains incurable. However, evidence suggests that effective anti-T2D drugs, such as the GLP-1 mimetic and neuroprotector liraglutide, can be also efficient against AD. Thus, we aimed to study the benefits of a peripheral liraglutide treatment in AD female mice. We used blood and brain cortical lysates from 10-month-old 3xTg-AD female mice, treated for 28 days with liraglutide (0.2 mg/kg, once/day) to evaluate parameters affected in AD (e.g., Aß and p-tau, motor and cognitive function, glucose metabolism, inflammation and oxidative/nitrosative stress). Despite the limited signs of cognitive changes in mature female mice, liraglutide only reduced their cortical Aß1-42 levels. Liraglutide partially attenuated brain estradiol and GLP-1 and activated PKA levels, oxidative/nitrosative stress and inflammation in these AD female mice. Our results support the earlier use of liraglutide as a potential preventive/therapeutic agent against the accumulation of the first neuropathological features of AD in females.

Subtle thinning of retinal layers without overt vascular and inflammatory alterations in a rat model of prediabetes.

Purpose: Diabetic retinopathy is a neurovascular disease characterized by increased permeability of the blood-retinal barrier, changes in the neural components of the retina, and low-grade chronic inflammation. Diabetic retinopathy is a major complication of diabetes; however, the impact of a prediabetic state on the retina remains to be elucidated. The aim of this study was to assess possible early retinal changes in prediabetic rats, by evaluating changes in the integrity of the blood-retinal barrier, the retinal structure, neural markers, and inflammatory mediators. Methods: Several parameters were analyzed in the retinas of Wistar rats that drank high sucrose (HSu; 35% sucrose solution during 9 weeks, the prediabetic animal model) and were compared with those of age-matched controls. The permeability of the blood-retinal barrier was assessed with the Evans blue assay, and the content of the tight junction proteins and neural markers with western blotting. Optical coherence tomography was used to evaluate retinal thickness. Cell loss at the ganglion cell layer was assessed with terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay and by evaluating the immunoreactivity of the Brn3a transcription factor. To assess retinal neuroinflammation, the mRNA expression and protein levels of inducible nitric oxide synthase isoform (iNOS), interleukin-1 beta (IL-1ß), and tumor necrosis factor (TNF) were evaluated. Iba1 and MHC-II immunoreactivity and translocator protein (TSPO) mRNA levels were assessed to study the microglial number and activation state. Results: The thickness of the inner retinal layers of the HSu-treated animals decreased. Nevertheless, no apoptotic cells were observed, and no changes in retinal neural markers were detected in the retinas of the HSu-treated animals. No changes were detected in the permeability of the blood-retinal barrier, as well as the tight junction protein content between the HSu-treated rats and the controls. In addition, the inflammatory parameters remained unchanged in the retina despite the tendency for an increase in the number of retinal microglial cells. Conclusions: In a prediabetic rat model, the retinal structure is affected by the thinning of the inner layers, without overt vascular and inflammatory alterations. The results suggest neuronal dysfunction (thinning of the inner retina) that may precede or anticipate the vascular and inflammatory changes. Subtle structural changes might be viewed as early disturbances in an evolving disease, suggesting that preventive strategies (such as the modification of diet habits) could be applied at this stage, before the progression toward irreversible dysfunction and damage to the retina.

Choroidal thickness changes stratified by outcome in real-world treatment of diabetic macular edema.

PURPOSE: The aim of this study was to evaluate subfoveal choroidal thickness (SFCT) as a marker of outcome in real-world treatment of diabetic macular edema (DME) and to correlate it with choroidal thicknesses (CT) collected around the fovea. METHODS: Prospective interventional case series included a total of 126 eyes from 126 patients with recently diagnosed DME treated with a 3-monthly loading dose of ranibizumab or aflibercept and PRN thereafter until 24 months (M). CT was manually measured in the central 3500 µm area, subfoveally (SFCT), at 1750 µm right and left from the center in the horizontal plane and at 1750 µm up and down from the center in the vertical plane, by OCT. Anatomic (10% decrease in central retinal thickness) and functional (gain ≥ 5 letters) responses were assessed using univariate and multivariate analyses. The areas under ROC curves were used to assess whether baseline SFCT was a predictor of outcome. RESULTS: CT significantly decreased in all follow-ups (3 months after the 3 injections' loading dose (3M), 6 months (6M), 12 months (12M), 18 months (18M), 24 months (24M)). SFCT and other CT parameters are correlated. SFCT decrease from baseline was related with treatment (p = 0.003 to p < 0.001) but not with anatomic (3M, p = 0.858; 6M p = 0.762) or functional response (3M, p = 0.746; 6M, p = 0.156). SFCT was not found to be predictive of anatomic (AUC = 0.575, p = 0.172) or functional (AUC = 0.515, p = 0.779) outcome. CONCLUSIONS: SFCT is a reliable marker of choroidal thickness. Baseline SFCT decreased with anti-VEGF treatment but did not predict DME outcome.

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina.

BACKGROUND: Neuropeptide Y (NPY) is a neuromodulator that is expressed in the retina. Increasing evidence suggests that NPY has pronounced anti-inflammatory effects, which might depend on the inhibition of dipeptidyl-peptidase-IV (DPP-IV). The aim of this study was to investigate the impact of type 1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model. METHODS: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2 weeks after DM onset, animals were treated orally with sitagliptin (5 mg/kg.day) for 2 weeks. The expression of NPY and NPY receptors (Y1 , Y2 and Y5 receptors) was measured by quantitative polymerase chain reaction, Western blot and/or enzyme-linked immunosorbent assay. The immunoreactivity of NPY and NPY receptors was evaluated by immunohistochemistry, and the [35 S]GTPγS binding assay was used to assess the functional binding of NPY receptors. RESULTS: DM decreased the mRNA levels of NPY in the retina, as well as the protein levels of NPY and Y5 receptor. No changes were detected in the localization of NPY and NPY receptors in the retina and in the functional binding of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin. CONCLUSION: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP-IV enzyme is not underlying the NPY changes detected in the retina induced by type 1 DM.

Opening eyes to nanomedicine: Where we are, challenges and expectations on nanotherapy for diabetic retinopathy.

People affected with ocular diseases will significantly increase over the next decades, and, consequently, a substantial increase in health costs is expected. Diabetic retinopathy is the most common chronic complication of diabetes. The treatment of eye diseases affecting the posterior segment, such as diabetic retinopathy, is quite challenging due to the anatomy, physiology and biochemistry of the eye. Therefore, the development of new therapeutics for posterior eye diseases has been a major focus of pharmaceutical research in the area of vision sciences. Several nanosystems already offer efficient solutions for ophthalmological conditions, targeting internal eye tissues, as the retina, and many novel products are expected to appear hereafter. This review provides an insight on nanoparticle-based solutions for therapies directed to posterior segment of the eye diseases, particularly diabetic retinopathy, the present scenario, and the demands and expectations for the future.

Stochastic Detection of MPSA-Gold Nanoparticles Using a α-Hemolysin Nanopore Equipped with a Noncovalent Molecular Adaptor.

We present the first study of a novel, more sensitive method for the characterization of nanoparticles (NPs). This approach combines detection via a protein nanopore with modification of its interaction behavior using a molecular adaptor. We identify different populations of 3-mercapto-1-propanesulfonate (MPSA)-modified-gold NPs using the biological nanopores α-hemolysin (αHL) and its M113N mutant equipped with a noncovalently bound γ-cyclodextrin molecule as a stochastic sensor. Identification takes place on the basis of the extent of current blockades and residence times. Here, we demonstrate that noncovalently attached adaptors can be used to change the sensing properties of αHL nanopores, allowing the detection and characterization of different populations of MPSA NPs. This is an advance in sensitivity and diversity of NP sensing, as well as a promising and reliable technology to characterize NPs by using protein nanopores.

Sensing single mixed-monolayer protected gold nanoparticles by the α-hemolysin nanopore.

Gold nanoparticles are widely used in various applications in fields including chemistry, engineering, biology, medicine, and electronics. These materials can be synthesized and modified with ligands containing different functional groups. Among nanoparticles' characteristics, chemical surface composition is likely to be a crucial feature, demanding robust analytical methodologies for its assessment. Single molecule analysis using the biological nanopores α-hemolysin and its E111A mutant is presented here as a promising methodology to stochastically sense organic monolayer protected gold-nanoparticles with different ligand shell compositions. By monitoring the ionic current across a single protein nanopore, differences in the physical and chemical characteristics (e.g., size, ligand shell composition, and arrangement) of individual nanoparticles can be distinguished based on the differences in the current blockade events that they cause. Such differences are observed in the spread of both the amplitude and duration of current blockades. These values cannot be correlated with a single physical characteristic. Instead the spread represents a measure of heterogeneity within the nanoparticle population. While our results compare favorably with the more traditional analytical methodologies, further work will be required to improve the accuracy of identification of the NPs and understand the spread of values within a nanoparticle preparation as well as the overlap between similar preparations.

The role of Lys147 in the interaction between MPSA-gold nanoparticles and the α-hemolysin nanopore.

Single channel recordings were used to determine the effect of direct electrostatic interactions between sulfonate-coated gold nanoparticles and the constriction of the Staphylococcus aureus α-hemolysin protein channel on the ionic current amplitude. We provide evidence that Lys147 of α-hemolysin can interact with the sulfonate groups at the nanoparticle surface, and these interactions can reversibly block 100% of the residual ionic current. Lys147 is normally involved in a salt bridge with Glu111. The capture of a nanoparticle leads to a partial current block at neutral pH values, but protonation of Glu111 at pH 2.8 results in a full current block when the nanoparticle is captured. At pH 2.8, we suggest that Lys147 is free to engage in electrostatic interactions with sulfonates at the nanoparticle surface. To verify our results, we engineered a mutation in the α-hemolysin protein, where Glu111 is substituted by Ala (E111A), thus removing Glu111-Lys147 interactions and facilitating Lys147-sulfonate electrostatic interactions. This mutation leads to a 100% current block at pH 2.8 and a 92% block at pH 8.0, showing that electrostatic interactions are formed between the nanopore and the nanoparticle surface. Besides demonstrating the effect of electrostatic interactions on cross channel ionic current, this work offers a novel approach to controlling open and closed states of the α-hemolysin nanopore as a function of external gears.

Nanoparticles as phytochemical carriers for cancer treatment: News of the last decade.

INTRODUCTION: The development and application of novel therapeutic medicines for the treatment of cancer are of vital importance to improve the diseases outcome and survival rate. One noteworthy treatment approach is the use of biologically active compounds present in natural products. Even though these phytocompounds present anti-inflammatory, antioxidant, and anticancer properties, their use is limited essentially due to poor systemic delivery, low bioavailability, and water solubility concerns. To make full use of the anticancer potential of natural products, these limitations need to be technologically addressed. In this sense, nanotechnology emerges as a promising drug delivery system strategy. AREAS COVERED: In this review, the benefits and potential of nanodelivery systems for natural products encapsulation as promising therapeutic approaches for cancer, which were developed during the last decade, are highlighted. EXPERT OPINION: The nanotechnology area has been under extensive research in the medical field given its capacity for improving the therapeutic potential of drugs by increasing their bioavailability and allowing a targeted delivery to the tumor site. Thereby, the nanoencapsulation of phytocompounds can have a direct impact on the recognized therapeutic activity of natural products towards cancer.

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation.

In general, erythrocytes are highly permeable to water, urea and glycerol. However, expression of aquaporin isoforms in erythrocytes appears to be species characteristic. In the present study, human (hRBC) and bovine (bRBC) erythrocytes were chosen for comparative studies due to their significant difference in membrane glycerol permeability. Osmotic water permeability (P(f)) at 23°C was (2.89 ± 0.37) × 10(-2) and (5.12 ± 0.61) × 10(-2)cms(-1) for human and bovine cells, respectively, with similar activation energies for water transport. Glycerol permeability (P(gly)) for human ((1.37 ± 0.26) × 10(-5)cms(-1)) differed in three orders of magnitude from bovine erythrocytes ((5.82 ± 0.37) × 10(-8)cms(-1)) that also showed higher activation energy for glycerol transport. When compared to human, bovine erythrocytes showed a similar expression pattern of AQP1 glycosylated forms on immunoblot analysis, though in slight higher levels, which could be correlated with the 1.5-fold larger P(f) found. However, AQP3 expression was not detectable. Immunofluorescence analysis confirmed the absence of AQP3 expression in bovine erythrocyte membranes. In conclusion, lack of AQP3 in bovine erythrocytes points to the lipid pathway as responsible for glycerol permeation and explains the low glycerol permeability and high E(a) for transport observed in ruminants.

Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer's Disease.

The concept 'the retina as a window to the brain' has been increasingly explored in Alzheimer´s disease (AD) in recent years, since some patients present visual alterations before the first symptoms of dementia. The retina is an extension of the brain and can be assessed by noninvasive methods. However, assessing the retina for AD diagnosis is still a matter of debate. Using the triple transgenic mouse model of AD (3xTg-AD; males), this study was undertaken to investigate whether the retina and brain (hippocampus and cortex) undergo similar molecular and cellular changes during the early stages (4 and 8 months) of the pathology, and if the retina can anticipate the alterations occurring in the brain. We assessed amyloid-beta (Aß) and hyperphosphorylated tau (p-tau) levels, barrier integrity, cell death, neurotransmitter levels, and glial changes. Overall, the retina, hippocampus, and cortex of 3xTg-AD are not significantly affected at these early stages. However, we detected a few differential changes in the retina and brain regions, and particularly a different profile in microglia branching in the retina and hippocampus, only at 4 months, where the number and length of the processes decreased in the retina and increased in the hippocampus. In summary, at the early stages of pathology, the retina, hippocampus, and cortex are not significantly affected but already present some molecular and cellular alterations. The retina did not mirror the changes detected in the brain, and these observations should be taking into account when using the retina as a potential diagnostic tool for AD.

Neuropeptide Y system mRNA expression changes in the hippocampus of a type I diabetes rat model.

BACKGROUND: Neuropeptide Y (NPY) plays a crucial role in many neurobiological functions, such as cognition and memory. Cognitive and memory impairment have been described in diabetic patients. The metabolism of NPY is determined by the activity of proteases, primarily dipeptidyl-peptidase-IV (DPP-IV). Therefore, DPP-IV inhibitors, such as sitagliptin, may modulate the function of NPY. In this study, we investigated the effect of type 1 diabetes and sitagliptin treatment on the regulation of the mRNA encoding for NPY and its receptors (Y1, Y2, and Y5 receptors) in the hippocampus. METHODS: Type 1 diabetes was induced in male Wistar rats by i.p. injection of streptozotocin. Starting two weeks after diabetes onset, animals were treated orally with sitagliptin (5mg/kg, daily) for two weeks. The mRNA expression of Npy and its receptors (Npy1r, Npy2r, and Npy5r) in the hippocampus was evaluated using in situ hybridization with 33P-labeled oligonucleotides. RESULTS: The mRNA expression of Npy, Npy1r and Npy5r was higher in the dentate gyrus, whereas Npy2r highest level was observed in the CA3 subregion. The mRNA expression of Npy, Npy1r and Npy5r in dentate gyrus, CA1 and CA3 was not affected by diabetes and/or by sitagliptin treatment. Type 1 diabetes increased the mRNA expression of Npy2r in the CA3 subregion, which was prevented by sitagliptin treatment. CONCLUSIONS: Our results show that type 1 diabetes, at early stages, induces mild changes in the NPY system in the hippocampus that were counteracted by sitagliptin treatment.

Emerging Trends in Nanomedicine for Improving Ocular Drug Delivery: Light-Responsive Nanoparticles, Mesoporous Silica Nanoparticles, and Contact Lenses.

Vision is the most dominant of our senses, and it is crucial in every stage of our lives. Ocular diseases, regardless of whether they cause vision impairment or not, lead to personal and financial hardships. The anatomy and physiology of the eye strongly limit the efficacy of current ocular drug delivery strategies. Nanotechnology has been the ground for the development of powerful strategies in several fields, namely in medicine. This review highlights emerging nanotechnology-based solutions for improving ocular drug delivery and thus the bioavailability and efficacy of drugs. We focus our review on ambitious but promising approaches currently emerging to leverage the efficacy of nanoparticle-based systems in ocular therapy: (i) light-responsive nanoparticles, which enable spatiotemporal control of drug release; (ii) mesoporous silica nanoparticles, which offer high surface area-to-volume ratio, simple surface modification, good biocompatibility, and improved bioavailability; and (iii) contact lenses, which serve as a compliant method of nanoparticles use and as drug delivery systems for the treatment of ocular diseases.

Choroidal and retinal structural, cellular and vascular changes in a rat model of Type 2 diabetes.

Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal changes in diabetes have been reported and several attempts were made to validate in vivo choroidal thickness (CT) as a marker of retinopathy. We aimed to study choroidal and retinal changes associated with retinopathy in an animal model of spontaneous Type 2 diabetes, Goto-Kakizaki (GK) rats. Sclerochoroidal whole mounts and cryosections were prepared from 52-week-old GK and age-matched control Wistar Han rats. CT was measured by optical coherence tomography. Microglia reactivity, pericyte and endothelial cells distribution, and immunoreactivity of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) were evaluated by immunofluorescence. Choroidal vessels were visualized by direct perfusion with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Choroidal vascular density was evaluated by fluorescence microscopy. GK rats had increased CT (58.40 ± 1.15 µm versus 50.90 ± 1.58 µm, p < 0.001), reduced vascular density of the choriocapillaris (CC) (p = 0.045), increased Iba1+ cells density in the outer retina (p = 0.003) and increased VEGFR2 immunoreactivity in most retinal layers (p = 0.021 to 0.037). Choroidal microglial cells and pericytes showed polarity in their distribution, sparing the innermost choroid. This cell-free gap in the inner choroid was more pronounced in GK rats. In summary, GK rats have increased CT with decreased vascular density in the innermost choroid, increased VEGFR2 immunoreactivity in the retina and increased Iba1+ cells density in the outer retina.

Nutrition Education in Portuguese Medical Students: Impact on the Attitudes and Knowledge.

INTRODUCTION: Nutrition has been underrepresented in the curriculum of many medical schools and therefore physicians do not feel adequately prepared to provide dietary counselling. The aim of the present study is to determine the impact of a Nutrition and Metabolism curricular unit on nutrition attitudes, knowledge and confidence on future clinical practice of medical students. MATERIAL AND METHODS: All the students enrolled in the curricular unit (2017/2018) were invited to complete a questionnaire assessing their nutritional knowledge and eating habits at the beginning and at the end of the semester (n = 310). RESULTS: Initially, students reported good eating habits and nutrition knowledge. These aspects improved at the end of the study. Moreover, students reported that they felt more confident to do dietary counselling after intervention. DISCUSSION: Most medical students answered affirmatively to all questions related with good habits or eating behaviours, and the acquisition of knowledge had an impact in specific attitudes. After the Nutrition and Metabolism classes the students felt able to provide dietary counselling in different clinical settings, but none of the students felt extremely confident about their competencies for dietary counselling. This can be due to the fact that the students involved were in the first year of the integrated master's degree in medicine, which is a preclinical year, and thus distant from the medical reality and from contact with patients. CONCLUSION: Nutrition education can have a positive impact on attitudes and eating behaviours, knowledge and in the perception of competencies for dietary counselling.

Introdução: A nutrição não tem sido uma prioridade no programa curricular de muitas escolas médicas e, portanto, os médicos não se sentem devidamente preparados para realizar aconselhamento alimentar. O objetivo deste estudo consiste em determinar o impacto do ensino de Nutrição e Metabolismo nas atitudes e comportamentos, conhecimento e confiança na prática clínica futura dos alunos de medicina. Material e Métodos: Todos os estudantes (n = 310) inscritos na unidade curricular (2017/2018) foram convidados a preencher um questionário, no início e no final do semestre, para avaliar os seus hábitos e conhecimentos alimentares. Resultados: Inicialmente, os estudantes apresentavam bons hábitos alimentares e um bom conhecimento nutricional. Não obstante, no final do estudo verificou-se que estes parâmetros melhoraram. Mais ainda, após a unidade curricular os estudantes sentiam-se mais confiantes para realizar aconselhamento nutricional. Discussão: Após a unidade curricular, a maioria dos estudantes respondeu afirmativamente às questões referentes a atitudes e comportamentos alimentares, sendo que a aquisição de novos conhecimentos pode ser responsável pelo aumento significativo de respostas afirmativas a determinadas questões. Os estudantes sentiram-se capazes de realizar aconselhamento alimentar em diferentes contextos clínicos, mas foram poucos os que reportaram sentir-se fortemente confiantes. Tal pode dever-se ao facto de frequentarem o primeiro ano do mestrado integrado em medicina, ano pré-clínico, sem contacto com a prática médica e com o doente. Conclusão: Pode verificar-se que o ensino de Nutrição numa escola médica teve impacto positivo nas atitudes e comportamentos alimentares, conhecimento e perceção de competências para a realização de aconselhamento nutricional.

Babesia bovis: effect of Albumax II and orotic acid in a low-serum in vitro culture.

Bovine serum is an essential factor for the continuous in vitro growth of Babesia bovis parasites. Culture media typically contain 40% (v/v) of bovine serum. In the present study assays with low-serum media were performed. The growth of B. bovis Mo7 was successively lower in media with 30%, 20% and, principally, with 10% of serum. Without serum, the parasites were not able to propagate. In media with 10% of serum, the supplementation with Albumax II improved visibly the growth of B. bovis at the end of each cycle. Regarding the addition of orotic acid, no considerable effect was observed in media with 20% or 10% of serum, with or without Albumax II. B. bovis parasites cultured in vitro in all these media maintain their typical morphology during the intraerythrocytic stages.

Retinal thinning of inner sub-layers is associated with cortical atrophy in a mouse model of Alzheimer's disease: a longitudinal multimodal in vivo study.

BACKGROUND: It has been claimed that the retina can be used as a window to study brain disorders. However, concerning Alzheimer's disease (AD), it still remains controversial whether changes occurring in the brain and retina are associated. We aim to understand when changes start appearing in the retina and brain, how changes progress, and if they are correlated. METHODS: We carried out a unique longitudinal study, at 4, 8, 12, and 16 months of age, in a triple transgenic mouse model of AD (3×Tg-AD), which mimics pathological and neurobehavioral features of AD, as we have already shown. Retinal structure and physiology were evaluated in vivo using optical coherence tomography and electroretinography. Brain visual cortex structure was evaluated in vivo using magnetic resonance imaging. RESULTS: The retinal thickness of 3×Tg-AD decreased, at all time points, except for the outer nuclear layer, where the opposite alteration was observed. Amplitudes in scotopic and photopic responses were increased throughout the study. Similarly, higher amplitude and lower phase values were observed in the photopic flicker response. No differences were found in the activity of retinal ganglion cells. Visual cortex gray matter volume was significantly reduced. CONCLUSIONS: Our results show that this animal model shows similar neural changes in the retina and brain visual cortex, i.e., retinal and brain thinning. Moreover, since similar changes occur in the retina and brain visual cortex, these observations support the possibility of using the eye as an additional tool (noninvasive) for early AD diagnosis and therapeutic monitoring.

Influence of obesity, parental history of diabetes, and genes in type 2 diabetes: A case-control study.

Obesity, parental history (PH) of type 2 diabetes (T2D), and genes play an important role in T2D development. However, the influence of each factor on T2D variability is unclear. This study aimed to investigate the influence of obesity (body mass index [BMI], waist/hip ratio), PH, and 16 single-nucleotide polymorphisms (SNPs) associated with T2D on T2D variability in Mexico, comparing 1234 non-diabetic controls and 1219 diabetic patients. To replicate the data, a case-control (n = 2904) and a cross-sectional (n = 1901) study were also included. In a multivariate logistic regression model, all factors accounted for only 27.3% of T2D variability: SNPs (8.4%); PH (11.8%) and obesity (7.1%). These factors contributed more in men (33.2%) than in women (25%), specifically when the disease was diagnosed before the age of 46 (46.7% vs. 30%). Genes played a substantially more important role in men than in women (14.9% vs. 5.5%), while obesity and PH played a similar role in both genders. Genes and PH appeared to play a greater role than obesity in T2D. However, obesity contribution was calculated at the time of recruitment and may be underestimated in patients because the BMI decreased linearly with the number of years with the disease. The data suggest that sexual hormones may play important roles in genes that are associated with T2D.