ElsevierConejero-Garcia, Á.; Rivero-Gimeno, H.; Moreno-Sáez, Y.; Vilarino-Feltrer, G.; Ortuño-Lizarán, I.; Vallés Lluch, A. (2017). Correlating synthesis parameters with physicochemical properties of poly(glycerol sebacate). AbstractPoly(glycerol sebacate), PGS, is an elastomeric biodegradable polyester increasingly proposed in a variety of biomedical applications. It is prepared by polycondensation of sebacic acid and glycerol in a first stage in which a prepolymer is obtained, followed by a curing to conveniently crosslink it. In this work, synthesis parameters such as the curing temperature and time, and the molar ratio between reactants, were systematically varied to correlate them with the physicochemical properties of the resulting polymer networks. The efficiency of each manufacturing process was quantified through the relative mass effectively crosslinked and insoluble in tetrahydrofuran. Infrared spectra gave an estimation of the ratio of non-condensed polar terminal groups. These results were correlated with swelling results, which in turn provided the means to calculate the chains density through Flory-Rehner equilibrium swelling equation for lightly crosslinked polymers. The role of the synthesis parameters on the physical state of the resulting polymers, as well as their proneness to hydrolyze, were followed. The results 2 obtained highlight the relevance of rinsing them following synthesis, to remove noncrosslinked chains that easily diffuse to the surrounding medium. Curing under mild conditions equimolar mixtures of sebacic acid and glycerol proved to lead to poorly crosslinked swellable networks, which hydrolyze easily in bulk mode. Alternative molar ratios yield sticky and difficult to handle materials at higher polyol fractions in the reactive mixture, whilst an excess of acid terminal groups leads to a faster mass loss by hydrolysis in aqueous media together with surface salts deposition, concomitant with a lesser cell viability in in vitro culture. PGS synthesized from an equimolar ratio between reactants and cured at 130ºC or higher, for 48 h or longer, show suitable features for their use in tissue engineering applications where hydrophobic surface-degradable rubbers are required, without significant differences among them.

These data suggest that phosphorylated α-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia. Therefore, the retina may provide an in vivo indicator of brain pathology severity, and its detection could help in the diagnosis and monitoring of disease progression. © 2018 International Parkinson and Movement Disorder Society.

Despite decades of research, accurate diagnosis of Parkinson's disease remains a challenge, and disease-modifying treatments are still lacking. Research into the early (presymptomatic) stages of Parkinson's disease and the discovery of novel biomarkers is of utmost importance to reduce this burden and to come to a more accurate diagnosis at the very onset of the disease. Many have speculated that non-motor symptoms could provide a breakthrough in the quest for early biomarkers of Parkinson's disease, including the visual disturbances and retinal abnormalities that are seen in the majority of Parkinson's disease patients. An expanding number of clinical studies have investigated the use of in vivo assessments of retinal structure, electrophysiological function, and vision-driven tasks as novel means for identifying patients at risk that need further neurological examination and for longitudinal follow-up of disease progression in Parkinson's disease patients. Often, the results of these studies have been interpreted in relation to α-synuclein deposits and dopamine deficiency in the retina, mirroring the defining pathological features of Parkinson's disease in the brain. To better understand the visual defects seen in Parkinson's disease patients and to propel the use of retinal changes as biomarkers for Parkinson's disease, however, more conclusive neuropathological evidence for the presence of retinal α-synuclein aggregates, and its relation to the cerebral α-synuclein burden, is urgently needed. This review provides a comprehensive and critical overview of the research conducted to unveil α-synuclein aggregates in the retina of Parkinson's disease patients and animal models, and thereby aims to aid the ongoing discussion about the potential use of the retinal changes and/or visual symptoms as biomarkers for Parkinson's disease.

This study proposes a new interpretation of the outer retinal bands that leads to a more accurate interpretation of OCT images, providing information about the health of cones and their relationship with the RPE, and could help to form a better understanding of retinal disease diagnosis and prognosis.

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Metal-organic frameworks (MOFs) have been evaluated as potential nanocarriers for intra-ocular incorporation of brimonidine tartrate to treat chronic glaucoma. Experimental results show that UiO-67 and MIL-100 (Fe) exhibit the highest loading capacity with values up to 50-60 wt.%, while the performance is quite limited for MOFs with narrow cavities (below 0.8 nm, e.g. UiO-66 and HKUST-1). The large loading capacity in UiO-67 is accompanied by an irreversible structural amorphization in aqueous and physiological media that promotes extended release kinetics above 12 days. Compared to the traditional drawbacks associated with the sudden release of the commercial drugs (e.g., ALPHAGAN), these results anticipate UiO-67 as a potential nanocarrier for drug delivery in intra-ocular therapeutics. These promising results are further supported by cytotoxicity tests using retinal photoreceptor cells (661W). Toxicity of these structures (including the metal nodes and organic ligands) for retinal cells is rather low for all samples evaluated, except for HKUST-1.

Parkinson’s disease (PD) patients often suffer from non-motor symptoms like sleep dysregulation, mood disturbances or circadian rhythms dysfunction. The melanopsin-containing retinal ganglion cells are involved in the control and regulation of these processes and may be affected in PD, as other retinal and visual implications have been described in the disease. Number and morphology of human melanopsin-containing retinal ganglion cells were evaluated by immunohistochemistry in eyes from donors with PD or control. The Sholl number of intersections, the number of branches, and the number of terminals from the Sholl analysis were significantly reduced in PD melanopsin ganglion cells. Also, the density of these cells significantly decreased in PD compared to controls. Degeneration and impairment of the retinal melanopsin system may affect to sleep and circadian dysfunction reported in PD pathology, and its protection or stimulation may lead to better disease prospect and global quality of life of patients.

Objective: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD. Methods: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human donors. Results: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells were not reduced in number, but they showed cellular alterations compromising their adequate function: (1) a loss of mitochondria inside their lobular appendages, which may indicate an energetic failure; and (2) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal transmission from the rod pathway. Interpretation: The dopaminergic system impairment and the affection of the rod pathway through the AII cells may explain and be partially responsible for the reduced contrast sensitivity or electroretinographic response described in PD. Also, dopamine reduction and the loss of synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell loss previously described and to the disturbances in circadian rhythm and sleep reported in PD patients. These data support the idea that the retina reproduces brain neurodegeneration and is highly involved in PD pathology.