Uncovering a Mutation-Independent Therapeutic Strategy against Inherited Retinal Diseases: Development of Class I HDAC/LSD1 Hybrid Inhibitors.

Among genetic retinal disorders, retinitis pigmentosa (RP) is characterized by degeneration of rod photoreceptors caused by a large number of diverse mutations, most of which act through different pathways to which epigenetic targets also contribute. The eraser enzymes lysine demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) play major roles in the development of rod photoreceptors, and their inhibitors were shown to block inherited rod degeneration, preserving vision and contributing to a general anti-inflammatory profile at the retinal level. In this work, we proposed the development of polypharmacological agents targeting class I HDAC/LSD1 enzymes with the aim of treating the mice model of RP.

In Vitro Evaluation of the Protective Efficacy of L. Waste for the Sustainable Development of Bioactive Phytocomplexes.

Saffron, branded as Repron, is effective in slowing the progression of several neurodegenerative diseases. Its production, however, requires specific cultivation techniques and procedures that, together with low yields, make it expensive. To address this challenge, hydroponic cultivation has been adopted.

The efficacy of Saffron Repron® in counteracting the progression of retinitis pigmentosa: Neuroprotection and resilience.

The mutations observed in the various forms of retinitis pigmentosa (RP) affect genes coding for rod-specific proteins and direct the progression of different forms of dystrophy toward total blindness. The present investigation aims to explore the protective effects of Saffron Repron®, in a mouse model of RP. Saffron was administered orally to pregnant females and weaned pups for 120 days.

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

Background: Photoreceptor death leads to inherited blinding retinal diseases, such as retinitis pigmentosa (RP). As disease progression often outpaces therapeutic advances, developing effective treatments is urgent. This study evaluates the efficacy of small peptides derived from pigment epithelium-derived factor (PEDF), which are known to restrict common cell death pathways associated with retinal diseases.

β-Cyclodextrin nanosponges for the ocular delivery of therapeutic Micro-RNA in a Mouse model of retinitis Pigmentosa: A proof of concept study.

The exploitation of micro-RNA (miR) sequences as therapeutics has become highly attractive for the treatment of several diseases, including those still lacking effective cures such as retinitis pigmentosa (RP). Interestingly, miR-155-5p plays a role in photo-oxidative inflammation in wild-type mice and is up-regulated in rd10 mice showing peak rod degeneration, suggesting its inhibition by the corresponding anti-miR as a viable therapeutic strategy for RP. However, biomedical application of (anti-)miRs is limited by their oligonucleotide nature, suffering from low solubility and bioavailability along with a very low half-life in vivo due to enzymatic degradation.

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.

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.

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).

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.

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 Ce/Ce 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 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.

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 Ce 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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.