Diabetic retinopathy (RD) is a microvascular disease that can cause the formation of fragile neovessels, increasing the risk of hemorrhages and leading to vision loss. Current therapies are based on the intravitreal injection of anti-VEGF (vascular endothelial growth factor), which is invasive and can cause secondary effects. The development of new treatments that complement the current therapies is necessary to improve the patient’s outcomes. Nanostructured formulations offer several advantages regarding drug delivery and penetration. In this research, a resveratrol nanosuspension (RSV-NS) was prepared and characterized using dynamic light scattering, field emission scanning electron microscopy, and infrared spectroscopy. The RSV-NS had an average particle size of 304.0 ± 81.21 nm with a PDI of 0.225 ± 0.036, and a spherical-like morphology and uniform particle distribution. Cell viability, proliferation, and migration were tested on endothelial cells (HMRECs). RSV-NS in a concentration of less than 18.75 µM did not have a cytotoxic effect on HMRECs. Likewise, proliferation and migration were significantly reduced compared to the unstimulated control at 37.5 µM. The RSV-NS did not present cytotoxic effects but decreased cell proliferation and migration, indicating that it could provide an important contribution to future medical implementations and could have a high potential to treat this disease.

Diabetes is a metabolic disorder characterized by a high level of glucose in the blood. Diabetes is projected to affect 366 million people by 2030, and the prevalence of diabetic retinopathy (DR) is expected to rise accordingly. DR is a multifactorial late-stage manifestation in diabetic patients. This hyperglycemia is potentially the leading cause of retinal vascular disorder. With DR consuming roughly 40% of the total cost of diabetes care in the US, it translates to approximately $120 billion annually in economic burden, not only from direct disease management costs but also from lost worker productivity. Although some treatments are available, there is no treatment yet that could fully attenuate clinical progression to reverse damage to the retina. These shortcomings make it imperative to explore non-invasive, novel, and cost-effective routes for treating DR since all the available techniques are invasive, expensive, and primarily associated with side effects. Specialized databases and Mesh (terms defined as keywords by the researchers) were consulted to search for information that gathered scientific evidence on the subject in the last decade. Some of the databases used were: National Center for Biotechnology Information (NCBI), ScienceDirect, Cochrane Library, SpringerLink, and Clinicaltrials, among others. This review focuses on the importance of developing non-invasive alternatives for the treatment of DR.

Two PSEN1 E280A carriers have presented extreme protection against autosomal dominant Alzheimer’s disease (ADAD), with over two decades of delay for dementia onset. One of them, a male heterozygous for the RELN-COLBOS protective variant showed increased neuronal density in the entorhinal cortex ¹ . We conducted a deep phenotyping and genotyping study of the entorhinal cortex in protected and unprotected PSEN1 E280A cases, sporadic AD, and non-demented controls. We used single nuclei and spatial transcriptomics, whole genome sequencing, and candidate genotype-associated expression changes (GAEC) analysis. Our results showed unique neuronal and oligodendrocytic populations in the male RELN-COLBOS patient. Unique RELN positive inhibitory interneurons were enriched in cortical Layer I, while unique abundant ADAMTSL1 positive excitatory neurons were distributed in Layers II/III and Layer Va. These neurons and mature myelinated oligodendrocytes benefitted from increased expression of LRP6 receptor, functioning as a non-canonical receptor for the mutated Reelin protein encoded by RELN-COLBOS . Finally, GAEC and pathway enrichment analyses suggested that other mutations enhanced RELN-COLBOS effects in oligodendrocytes in the male RELN-COLBOS patient, explaining the phenotypic differences with his sister, a RELN-COLBOS carrier with no evident protection from ADAD. Our findings suggest that extreme deviations of the PSEN1 E280A phenotype are more likely attributed to oligogenic effects, including simultaneous mutations occurring in genes including ITGA2, involved in single molecular pathways, such as the Integrins / Focal Adhesion pathway, as potential disease modifiers for Alzheimer’s disease (AD).

Diabetes is a metabolic disorder characterized by a high level of glucose in the blood. Diabetes is projected to affect 366 million people by 2030, and the prevalence of diabetic retinopathy (DR) is expected to rise accordingly. DR is a multifactorial late-stage manifestation in diabetic patients. This hyperglycemia is potentially the leading cause of retinal vascular disorder. With DR consuming roughly 40% of the total cost of diabetes care in the US, it translates to approximately $120 billion annually in economic burden, not only from direct disease management costs but also from lost worker productivity. Although some treatments are available, there is no treatment yet that could fully attenuate clinical progression to reverse damage to the retina. These shortcomings make it imperative to explore non-invasive, novel, and cost-effective routes for treating DR since all the available techniques are invasive, expensive, and primarily associated with side effects. Specialized databases and Mesh (terms defined as keywords by the researchers) were consulted to search for information that gathered scientific evidence on the subject in the last decade. Some of the databases used were: National Center for Biotechnology Information (NCBI), ScienceDirect, Cochrane Library, SpringerLink, and Clinicaltrials, among others. This review focuses on the importance of developing non-invasive alternatives for the treatment of DR.