H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.

Photoreceptor death causes blinding inheritable retinal diseases, such as retinitis pigmentosa (RP). As disease progression often outpaces therapeutic advances, finding effective treatments is urgent. This study focuses on developing a targeted approach by evaluating the efficacy of small peptides derived from pigment epithelium-derived factor (PEDF), known to restrict common cell death pathways associated with retinal diseases. Peptides with affinity for the PEDF receptor, PEDF-R, (17-mer and H105A) delivered via eye drops reached the retina, efficiently promoted photoreceptor survival, and improved retinal function in RP mouse models based on both the rd10 mutation and the rhodopsin P23H mutation. Additionally, intravitreal delivery of AAV-H105A vectors delayed photoreceptor degeneration in the latter RP mouse model. Furthermore, peptide H105A specifically prevented photoreceptor death induced by oxidative stress, a contributing factor to RP progression, in human retinal organoids. This promising approach for peptide eye drop delivery holds significant potential as a therapeutic for preventing photoreceptor death in retinal disorders, offering a high safety profile, low invasiveness and multiple delivery options.

Targeting Relevant HDACs to Support the Survival of Cone Photoreceptors in Inherited Retinal Diseases: Identification of a Potent Pharmacological Tool with In Vitro and In Vivo Efficacy.

Inherited retinal diseases, which include retinitis pigmentosa, are a family of genetic disorders characterized by gradual rod-cone degeneration and vision loss, without effective pharmacological treatments. Experimental approaches aim to delay disease progression, supporting cones' survival, crucial for human vision. Histone deacetylases (HDACs) mediate the activation of epigenetic and nonepigenetic pathways that modulate cone degeneration in RP mouse models. We developed new HDAC inhibitors (5a-p), typified by a tetrahydro-γ-carboline scaffold, characterized by high HDAC6 inhibition potency with balanced physicochemical properties for in vivo studies. Compound 5d (repistat, IC50 HDAC6 = 6.32 nM) increased the levels of acetylated α-tubulin compared to histone H3 in ARPE-19 and 661W cells. 5d promoted vision rescue in the atp6v0e1-/- zebrafish model of photoreceptor dysfunction. A single intravitreal injection of 5d in the rd10 mouse model of RP supported morphological and functional preservation of cone cells and maintenance of the retinal pigment epithelium array.

Cell Electrokinetic Fingerprint: A Novel Approach Based on Optically Induced Dielectrophoresis (ODEP) for In-Flow Identification of Single Cells.

A novel optically induced dielectrophoresis (ODEP) system that can operate under flow conditions is designed for automatic trapping of cells and subsequent induction of 2D multi-frequency cell trajectories. Like in a "ping-pong" match, two virtual electrode barriers operate in an alternate mode with varying frequencies of the input voltage. The so-derived cell motions are characterized via time-lapse microscopy, cell tracking, and state-of-the-art machine learning algorithms, like the wavelet scattering transform (WST). As a cell-electrokinetic fingerprint, the dynamic of variation of the cell displacements happening, over time, is quantified in response to different frequency values of the induced electric field. When tested on two biological scenarios in the cancer domain, the proposed approach discriminates cellular dielectric phenotypes obtained, respectively, at different early phases of drug-induced apoptosis in prostate cancer (PC3) cells and for differential expression of the lectine-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcript levels in human colorectal adenocarcinoma (DLD-1) cells. The results demonstrate increased discrimination of the proposed system and pose an additional basis for making ODEP-based assays addressing cancer heterogeneity for precision medicine and pharmacological research.

Blue Light Damage and p53: Unravelling the Role of p53 in Oxidative-Stress-Induced Retinal Apoptosis.

In the digital age, the widespread presence of electronic devices has exposed humans to an exceptional amount of blue light (BL) emitted from screens, LEDs, and other sources. Studies have shown that prolonged exposure to BL could have harmful effects on the visual system and circadian rhythm regulation. BL is known to induce oxidative stress, leading to DNA damage. Emerging research indicates that BL may also induce cell death pathways that involve the tumor-suppressor protein p53. Activated p53 acts as a transcription factor to regulate the expression of genes involved in cell cycle arrest, DNA repair, and apoptosis. This study aimed to explore the implication of p53 in BL-caused retinal damage, shedding light on the potential mechanisms of oxidative-stress-induced retinal diseases. BL-exposed porcine retinal cultures demonstrated increased p53- and caspase-mediated apoptosis, depending on exposure duration. Direct inhibition of p53 via pifithrin α resulted in the prevention of retinal cell death. These findings raise concerns about the long-term consequences of the current daily BL exposure and its potential involvement in various pathological conditions, including oxidative-stress-based retinal diseases like age-related macular degeneration. In addition, this study paves the way for the development of novel therapeutic approaches for oxidative-stress-based retinal diseases.

Anti-inflammatory reprogramming of microglia cells by metabolic modulators to counteract neurodegeneration; a new role for Ranolazine.

Microglia chronic activation is a hallmark of several neurodegenerative diseases, including the retinal ones, possibly contributing to their etiopathogenesis. However, some microglia sub-populations have anti-inflammatory and neuroprotective functions, thus making arduous deciphering the role of these cells in neurodegeneration. Since it has been proposed that functionally different microglia subsets also rely on different metabolic routes, we hypothesized that modulating microglia metabolism might be a tool to enhance their anti-inflammatory features. This would have a preventive and therapeutic potential in counteracting neurodegenerative diseases. For this purpose, we tested various molecules known to act on cell metabolism, and we revealed the anti-inflammatory effect of the FDA-approved piperazine derivative Ranolazine on microglia cells, while confirming the one of the flavonoids Quercetin and Naringenin, both in vitro and in vivo. We also demonstrated the synergistic anti-inflammatory effect of Quercetin and Idebenone, and the ability of Ranolazine, Quercetin and Naringenin to counteract the neurotoxic effect of LPS-activated microglia on 661W neuronal cells. Overall, these data suggest that using the selected molecules -also in combination therapies- might represent a valuable approach to reduce inflammation and neurodegeneration while avoiding long term side effects of corticosteroids.

The Impressive Anti-Inflammatory Activity of Cerium Oxide Nanoparticles: More than Redox?

Cerium oxide nanoparticles (CNPs) are biocompatible nanozymes exerting multifunctional biomimetic activities, including superoxide dismutase (SOD), catalase, glutathione peroxidase, photolyase, and phosphatase. SOD- and catalase-mimesis depend on Ce3+/Ce4+ redox switch on nanoparticle surface, which allows scavenging the most noxious reactive oxygen species in a self-regenerating, energy-free manner. As oxidative stress plays pivotal roles in the pathogenesis of inflammatory disorders, CNPs have recently attracted attention as potential anti-inflammatory agents. A careful survey of the literature reveals that CNPs, alone or as constituents of implants and scaffolds, strongly contrast chronic inflammation (including neurodegenerative and autoimmune diseases, liver steatosis, gastrointestinal disorders), infections, and trauma, thereby ameliorating/restoring organ function. By general consensus, CNPs inhibit inflammation cues while boosting the pro-resolving anti-inflammatory signaling pathways. The mechanism of CNPs' anti-inflammatory effects has hardly been investigated, being rather deductively attributed to CNP-induced ROS scavenging. However, CNPs are multi-functional nanozymes that exert additional bioactivities independent from the Ce3+/Ce4+ redox switch, such as phosphatase activity, which could conceivably mediate some of the anti-inflammatory effects reported, suggesting that CNPs fight inflammation via pleiotropic actions. Since CNP anti-inflammatory activity is potentially a pharmacological breakthrough, it is important to precisely attribute the described effects to one or another of their nanozyme functions, thus achieving therapeutic credibility.

A Window to the Brain: The Retina to Monitor the Progression and Efficacy of Saffron Repron® Pre-Treatment in an LPS Model of Neuroinflammation and Memory Impairment.

A mechanism shared by most neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD), is neuroinflammation. It has been shown to have a link between cognitive impairment and retinal function under neuroinflammatory conditions, confirming the essential role of the retina as a window to the brain. Here, we characterize a mouse model of LPS-induced neuroinflammation describing the parallel deterioration of both memory and visual function. Then, we demonstrate, using the Novel Object Recognition test (NOR) and electroretinogram (ERG) recordings, that preventive, chronic treatment with saffron Repron® is able to reduce the neuroinflammation process and prevent the impairment of both cognitive and visual function. The improvement in behavioral and visual function is confirmed by the pattern of expression of neuroinflammation-related genes and related proteins where pre-treatment with Repron® saffron presents a positive modulation compared with that obtained in animals treated with LPS alone. These results hold for retinal tissue and partially in the brain, where it appears that the onset of damage was delayed. This trend underlines the critical role of the retina as a most sensitive portion of the central nervous system to LPS-induced damage and could be used as a "sensor" for the early detection of neurodegenerative diseases such as Alzheimer's.

Safe-Shields: Basal and Anti-UV Protection of Human Keratinocytes by Redox-Active Cerium Oxide Nanoparticles Prevents UVB-Induced Mutagenesis.

Cerium oxide nanoparticles (nanoceria), biocompatible multifunctional nanozymes exerting unique biomimetic activities, mimic superoxide-dismutase and catalase through a self-regenerating, energy-free redox cycle driven by Ce3+/4+ valence switch. Additional redox-independent UV-filter properties render nanoceria ideal multitask solar screens, shielding from UV exposure, simultaneously protecting tissues from UV-oxidative damage. Here, we report that nanoceria favour basal proliferation of primary normal keratinocytes, and protects them from UVB-induced DNA damage, mutagenesis, and apoptosis, minimizing cell loss and accelerating recovery with flawless cells. Similar cell-protective effects were found on irradiated noncancerous, but immortalized, p53-null HaCaT keratinocytes, with the notable exception that here, nanoceria do not accelerate basal HaCaT proliferation. Notably, nanoceria protect HaCaT from oxidative stress induced by irradiated titanium dioxide nanoparticles, a major active principle of commercial UV-shielding lotions, thus neutralizing their most critical side effects. The intriguing combination of nanoceria multiple beneficial properties opens the way for smart and safer containment measures of UV-induced skin damage and carcinogenesis.

Androgen Deprivation Freezes Hormone-Sensitive Prostate Cancer Cells in a Reversible, Genetically Unstable Quasi-Apoptotic State, Bursting into Full Apoptosis upon Poly(ADP-ribose) Polymerase Inhibition.

Androgen deprivation therapy (ADT) is a powerful treatment for metastatic hormone-sensitive prostate cancer (mHSPC) patients, but eventually and inevitably, cancer relapses, progressing to the fatal castration-resistant (CR)PC stage. Progression implies the emergence of cells proliferating in the absence of androgen through still elusive mechanisms. We show here for the first time that ADT induces LNCaP mHSPC cells to collectively enter a metastable quasi-apoptotic state (QUAPS) consisting of partial mitochondrial permeabilization, limited BAX and caspase activation, and moderate induction of caspase-dependent dsDNA breaks; despite this, cells maintain full viability. QUAPS is destabilized by poly(ADP)-polymerase inhibition (PARPi), breaking off toward overt intrinsic apoptosis and culture extinction. Instead, QUAPS is rapidly and efficiently reverted upon androgen restoration, with mitochondria rapidly recovering integrity and cells collectively resuming normal proliferation. Notably, replication restarts before DNA repair is completed, and implies an increased micronuclei frequency, indicating that ADT promotes genetic instability. The recovered cells re-acquire insensitivity to PARPi (as untreated LNCaP), pointing to specific, context-dependent vulnerability of mHSPC cells to PARPi during ADT. Summarizing, QUAPS is an unstable, pro-mutagenic state developing as a pro-survival pathway stabilized by PARP, and constitutes a novel viewpoint explaining how ADT-treated mHSPC may progress to CRPC, indicating possible preventive countermeasures.

Efficacy of Hydroponically Cultivated Saffron in the Preservation of Retinal Pigment Epithelium.

Saffron treatment is a broad-spectrum therapy used for several retinal diseases, and its effectiveness depends on a particular molecular composition (REPRON® saffron). Its production requires specific crops and procedures that, together with low yields, make this spice expensive. To reduce costs, the use of hydroponic crops is gradually increasing. In this study, we tested the protective properties of a hydroponic saffron (sH) batch in models of retinal pigmented epithelium (RPE) degeneration. ARPE-19 cells were pretreated with 40 µg/mL saffron and exposed to different types of damage: excess light and retinol (LE + RET) or oxidative stress (H2O2). After analyzing the composition of all saffron types with spectroscopy, we performed cell viability and immunofluorescence analysis for both protocols. We compared the sH results with those of a validated batch of saffron REPRON® (sR) and those of a saffron non-REPRON® (sNR) batch. sH and sR, which we found had the same chemical composition, were more effective than sNR in increasing cell survival and attenuating the morphological changes related to apoptosis. In conclusion, hydroponic culturing is a suitable strategy to produce high-quality saffron to reduce costs and increase the accessibility of this promising treatment for retinal degeneration.

Clinical parameters obtained during tear film examination in domestic rabbits.

BACKGROUND: One of the contributing factors to ocular surface health is a stable precorneal tear film. Considering the increasing interest in rabbits as pets and the limited literature available on domestic rabbit tearing, the aim of this study was to establish normative data for examination of the tear film in domestic rabbits. RESULTS: The study included 75 client-owned domestic Holland Lop rabbits (150 eyes). The following examinations were performed in each eye: Schirmer tear test-1, tear osmometry, interferometry, tear meniscus height measurement and meibography (quantifying meibomian gland loss as a percentage). The resulting median (95% central range) values were 10.0 (5.0-17.3) mm/min for the Schirmer tear test-1, 345.0 (280.5-376.1) mOsm/L for tear osmolarity, grade 2 (1-4) of interferometry, 0.28 (0.20-0.47) mm for tear meniscus height and 0.0 (0.0-67.6) % meibomian gland loss. A significant association was found between tear osmolarity and age, with an estimated decrease of - 4.0 mOsm/L with each additional year of age (p < 0.001). The distributions of interferometry grades were significantly different between males and females (p < 0.001), with grade 1 and grade 2 being the most frequent in females and males, respectively. A weak negative correlation was also observed between interferometry grade and the percentage of meibomian gland loss (r = - 0.22, p = 0.006). CONCLUSIONS: This is an original study that documents extensive tear film parameters in healthy Holland Lop rabbits. The results can be used as normative data for the examination of the tear film in this lagomorph breed.

Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration.

The 18 kDa translocator protein (TSPO) is predominantly located in the mitochondrial outer membrane, playing an important role in steroidogenesis, inflammation, survival, and cell proliferation. Its expression in the CNS, and mainly in glial cells, is upregulated in neuropathologies and brain injury. In this study, the potential of targeting TSPO for the therapeutic treatment of inflammatory-based retinal neurodegeneration was evaluated by means of an in vitro model of lipopolysaccharide (LPS)-induced degeneration in 661 W cells, a photoreceptor-like cell line. After the assessment of the expression of TSPO in 661W cells, which, to the best of our knowledge, was never investigated so far, the anti-inflammatory and cytoprotective effects of a number of known TSPO ligands, belonging to the class of N,N-dialkyl-2-arylindol-3-ylglyoxylamides (PIGAs), were evaluated, using the classic TSPO ligand PK11195 as the reference standard. All tested PIGAs showed the ability to modulate the inflammatory and apoptotic processes in 661 W photoreceptor-like cells and to reduce LPS-driven cellular cytotoxicity. The protective effect of PIGAs was, in all cases, reduced by cotreatment with the pregnenolone synthesis inhibitor SU-10603, suggesting the involvement of neurosteroids in the protective mechanism. As inflammatory processes play a crucial role in the retinal neurodegenerative disease progression toward photoreceptors' death and complete blindness, targeting TSPO might represent a successful strategy to slow down this degenerative process that may lead to the inexorable loss of vision.

Medicinal Hypervalent Tellurium Prodrugs Bearing Different Ligands: A Comparative Study of the Chemical Profiles of AS101 and Its Halido Replaced Analogues.

Ammonium trichloro (dioxoethylene-O,O') tellurate (AS101) is a potent immunomodulator prodrug that, in recent years, entered various clinical trials and was tested for a variety of potential therapeutic applications. It has been demonstrated that AS101 quickly activates in aqueous milieu, producing TeOCl3-, which likely represents the pharmacologically active species. Here we report on the study of the activation process of AS101 and of two its analogues. After the synthesis and characterization of AS101 and its derivatives, we have carried out a comparative study through a combined experimental and computational analysis. Based on the obtained results, we describe here, for the first time, the detailed reaction that AS101 and its bromido- and iodido-replaced analogues undergo in presence of water, allowing the conversion of the original molecule to the likely true pharmacophore. Interestingly, moving down in the halogens' group we observed a higher tendency to react, attributable to the ligands' effect. The chemical and mechanistic implications of these meaningful differences are discussed.

Design, Synthesis, and In Vitro Evaluation of Novel 8-Amino-Quinoline Combined with Natural Antioxidant Acids.

Overproduction of reactive oxygen species (ROS) and alterations in metallostasis are common and related hallmarks in several neurodegenerative diseases (NDDs). Nature-based derivatives always represent an attractive tool in MTDL drug design, especially against ROS in NDDs. On this notion, we designed a new series of 8-quinoline-N-substituted derivatives with a natural antioxidant portion (i.e., lipoic, caffeic, and ferulic acids). These compounds were shown to chelate copper, a metal involved in ROS-induced degeneration, and scavenger oxygen radicals in DPPH assay. Then, selected compounds 4 and 5 were evaluated in an in vitro model of oxidative stress and shown to possess cytoprotective effects in 661W photoreceptor-like cells. The obtained results may represent a starting point for the application of the proposed class of compounds in retinal neurodegenerative diseases such as retinitis pigmentosa (RP), comprising a group of hereditary rod-cone dystrophies that represent a major cause of blindness in patients of working age, where the progression of the disease is a multifactorial event, with oxidative stress contributing predominantly.

Nutraceutical Molecules Slow Down Retinal Degeneration, in Tvrm4 Mice a Model of Retinitis Pigmentosa, by Genetic Modulation of Anti-oxidant Pathway.

Rhodopsin (RHO) mutations are responsible for 25-40% of the dominant cases of retinitis pigmentosa (RP) with different severity and progression rates. The Tvrm4 mice, heterozygous for an I307N dominant mutation of RHO, display a normal retinal phenotype when raised in ambient light conditions, but undergo photoreceptor degeneration when briefly exposed to strong white light. Here, The Tvrm4 mice is pre-treated with naringenin 100 mg/kg/die, quercetin 100 mg/kg/die, naringenin 50 + quercercetin 100 mg/kg/die or vehicle dimethyl sulfoxide (DMSO 0.025%) in the drinking water for 35 days. On the 30th day, retinal degeneration was induced by exposure for 1 min to the white light of 12,000 lux intensity, and the treatment was repeated for another 5 days. At the end of the protocol retinal functionality was tested by recording an electroretinogram (ERG). The retinal tissue was collected and was used for further analyses, including immunohistochemically, biochemical, and molecular biology assays. The data obtained show that treatment with nutraceutical molecules is effective in counteracting retinal degeneration by preserving the functionality of photoreceptors and increasing the antioxidant and anti-apoptotic pathways of retinal cells. The present data confirm that nutraceutical molecules are effective in slowing photoreceptor degeneration in a mutation-independent way by modulating the antioxidant response of the retina at the gene expression level.

Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer.

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the relationship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC).

Metabolic Reprogramming of Castration-Resistant Prostate Cancer Cells as a Response to Chemotherapy.

Prostate cancer at the castration-resistant stage (CRPC) is a leading cause of death among men due to resistance to anticancer treatments, including chemotherapy. We set up an in vitro model of therapy-induced cancer repopulation and acquired cell resistance (CRAC) on etoposide-treated CRPC PC3 cells, witnessing therapy-induced epithelial-to-mesenchymal-transition (EMT) and chemoresistance among repopulating cells. Here, we explore the metabolic changes leading to chemo-induced CRAC, measuring the exchange rates cell/culture medium of 36 metabolites via Nuclear Magnetic Resonance spectroscopy. We studied the evolution of PC3 metabolism throughout recovery from etoposide, encompassing the degenerative, quiescent, and repopulating phases. We found that glycolysis is immediately shut off by etoposide, gradually recovering together with induction of EMT and repopulation. Instead, OXPHOS, already high in untreated PC3, is boosted by etoposide to decline afterward, though stably maintaining values higher than control. Notably, high levels of EMT, crucial in the acquisition of chemoresistance, coincide with a strong acceleration of metabolism, especially in the exchange of principal nutrients and their end products. These results provide novel information on the energy metabolism of cancer cells repopulating from cytotoxic drug treatment, paving the way for uncovering metabolic vulnerabilities to be possibly pharmacologically targeted and providing novel clinical options for CRPC.

The use of acellular porcine corneal stroma xenograft (BioCorneaVet™ ) for the treatment of deep stromal and full thickness corneal defects: A retrospective study of 40 cases (2019-2021).

OBJECTIVE: To document the effectiveness and outcome of corneal grafting using acellular porcine corneal stroma (APCS) for veterinary use (BioCorneaVet™ ) to restore corneal integrity in dogs. METHODS: A review of medical records of patients that underwent keratoplasty with APCS graft to repair deep corneal defects, descemetoceles, and perforations between 2019 and 2021 was carried out. Only animals with intact dazzle reflex, consensual PLR before the surgery and a minimum follow-up of four weeks were considered for the study, with forty dogs (1 eye each) meeting the inclusion criteria. RESULTS: Brachycephalic breeds were the most frequently represented, and 20 right eyes and 20 left eyes were affected with 25 perforations, 8 descemetoceles, and 9 deep stromal defects (1 eye had both perforation and descemetocele). Most of the patients had concurrent ocular diseases or had undergone previous surgery on the other eye. Two different thickness of xenograft was used (300 or 450 µm), and the diameter ranged from 3 to 10 mm. Postoperative complications included mild to severe corneal vascularization, partial dehiscence, melting, and glaucoma. Follow-up time ranged from 28 to 797 days (mean: 233 days). Ocular integrity was maintained in 37/40 cases (92.5%), and vision was preserved in 36 cases (90%). CONCLUSION: The use of APCS (BioCorneaVet™ ) is an effective surgical treatment for deep stromal defects, descemetocele, and perforations in dogs, providing a good tectonic support and preserving anatomical integrity and vision. The cosmetic appearance was considered good in all the cases and continued to improve with time.

NeuriTES. Monitoring neurite changes through transfer entropy and semantic segmentation in bright-field time-lapse microscopy.

One of the most challenging frontiers in biological systems understanding is fluorescent label-free imaging. We present here the NeuriTES platform that revisits the standard paradigms of video analysis to detect unlabeled objects and adapt to the dynamic evolution of the phenomenon under observation. Object segmentation is reformulated using robust algorithms to assure regular cell detection and transfer entropy measures are used to study the inter-relationship among the parameters related to the evolving system. We applied the NeuriTES platform to the automatic analysis of neurites degeneration in presence of amyotrophic lateral sclerosis (ALS) and to the study of the effects of a chemotherapy drug on living prostate cancer cells (PC3) cultures. Control cells have been considered in both the two cases study. Accuracy values of 93% and of 92% are achieved, respectively. NeuriTES not only represents a tool for investigation in fluorescent label-free images but demonstrates to be adaptable to individual needs.

Retinal Neurodegeneration: Correlation between Nutraceutical Treatment and Animal Model.

Retinal diseases can be induced by a variety of factors, including gene mutations, environmental stresses and dysmetabolic processes. The result is a progressive deterioration of visual function, which sometimes leads to blindness. Many treatments are under investigation, though results are still mostly unsatisfactory and restricted to specific pathologies, particularly in the case of gene therapy. The majority of treatments have been tested in animal models, but very few have progressed to human clinical trials. A relevant approach is to study the relation between the type of treatments and the degenerative characteristics of the animal model to better understand the effectiveness of each therapy. Here we compare the results obtained from different animal models treated with natural compounds (saffron and naringenin) to anticipate the potentiality of a single treatment in different pathologies.