Synthesis and Evaluation of Glucosyl-, Acyl- and Silyl- Resveratrol Derivatives as Retinoprotective Agents: Piceid Octanoate Notably Delays Photoreceptor Degeneration in a Retinitis Pigmentosa Mouse Model.

Background: Retinitis pigmentosa (RP), the leading cause of inherited blindness in adults, is marked by the progressive degeneration of rod photoreceptors in the retina. While gene therapy has shown promise in treating RP in patients with specific mutations, no effective therapies currently exist for the majority of patients with diverse genetic backgrounds. Additionally, no intervention can yet prevent or delay photoreceptor loss across the broader RP patient population.

Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice.

Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against HO oxidative stress and in rd10 mice.

Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa.

Background: Gene therapy is a therapeutic possibility for retinitis pigmentosa (RP), in which therapeutic transgenes are currently delivered to the retina by adeno-associated viral vectors (AAVs). Although their safety and efficacy have been demonstrated in both clinical and preclinical settings, AAVs present some technical handicaps, such as limited cargo capacity and possible immunogenicity in repetitive doses. The development of alternative, non-viral delivery platforms like nanoparticles is of great interest to extend the application of gene therapy for RP.

Nanofibrous Matrix of Defined Composition Sustains Human Induced Pluripotent Stem Cell Culture.

Human induced pluripotent stem cells (hiPSCs) represent the most promising biological material for regenerative medicine applications. In this work, a 3D solid nanofibrous matrix of defined composition (Colamigel-S) consisting of 97 wt % gelatin, 2.6 wt % atelocollagen, and 0.

Biocompatibility Study of a Commercial Printed Circuit Board for Biomedical Applications: Lab-on-PCB for Organotypic Retina Cultures.

Printed circuit board (PCB) technology is well known, reliable, and low-cost, and its application to biomedicine, which implies the integration of microfluidics and electronics, has led to Lab-on-PCB. However, the biocompatibility of the involved materials has to be examined if they are in contact with biological elements. In this paper, the solder mask (PSR-2000 CD02G/CA-25 CD01, Taiyo Ink (Suzhou) Co.

Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy.

Mutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease.

Generation of the human iPSC line ESi082-A from a patient with macular dystrophy associated to mutations in the CRB1 gene.

Retinal dystrophies associated to mutations in the CRB1 gene comprise a wide array of clinical presentations. A blood sample from a patient with a family history of CRB1-retinal dystrophy was used to prepare the iPSC line ESi082-A. The genotype of the donor, affected of a perifoveal-bilateral macular dystrophy includes one frameshift deletion and one hypomorphic allele.

Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins.

Background: Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease.

Methods: In this study, we have analyzed a mouse model containing the p.

The Resveratrol Prodrug JC19 Delays Retinal Degeneration in rd10 Mice.

It has been reported that resveratrol (RES) has a therapeutic effect in different neurodegenerative and ocular diseases. However, RES is rapidly eliminated from the organism, and high doses need to be administered resulting in potential toxic side effects. We hypothesized that a RES prodrug such as 3,4'-diglucosyl resveratrol (JC19) would reduce RES metabolism to produce a neuroprotective effect.

Generation of a human iPS cell line (CABi003-A) from a patient with age-related macular degeneration carrying the CFH Y402H polymorphism.

Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries and is characterized by progressive degeneration of the macula, the central region of the retina. A human induced pluripotent stem cell (hiPSC) line was derived from peripheral blood mononuclear cells (PBMCs) from a patient with a clinical diagnosis of dry AMD carrying the CFH Y402H polymorphism. Sendai virus was using for reprogramming and the pluripotent and differentiation capacity of the cells were assessed by immunocytochemistry and RT-PCR.

Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose.

In the promising field of cellular therapy for retinal degenerative diseases, a new biomaterial is proposed as a scaffold to grow and surgically introduce a monolayer of retinal pigment epithelial cells into the subretinal space, keeping the orientation of the cells for a proper functional integration of the transplant. The use of induced pluripotent stem cells as the starting material for retinal pigment epithelial cells is intended to advance toward a personalized medicine approach.

Generation and characterization of the human iPSC line CABi001-A from a patient with retinitis pigmentosa caused by a novel mutation in PRPF31 gene.

PRPF31 gene codes for a ubiquitously expressed splicing factor but mutations affect exclusively the retina, producing the progressive death of photoreceptor cells. We have identified a novel PRPF31 mutation in a patient with autosomal dominant retinitis pigmentosa. A blood sample was obtained and mononuclear cells were reprogrammed using the non-integrative Sendai virus to generate the cell line CABi001-A.

Generation of a human iPS cell line from a patient with retinitis pigmentosa due to EYS mutation.

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease. Mutations in EYS have been associated with autosomal recessive RP. The human iPS cell line, CABi002-A, derived from peripheral blood mononuclear cells from a patient carrying a heterozygous double mutation in EYS gene was generated by non-integrative reprogramming technology, using hOCT3/4, hSOX2, hc-MYC and hKLF4 reprogramming factors.

Rasagiline delays retinal degeneration in a mouse model of retinitis pigmentosa via modulation of Bax/Bcl-2 expression.

Aims: Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive degeneration of rod photoreceptors. An imbalance between pro- and antiapoptotic factors, such as Bax/Bcl-2, has been involved in retinal degeneration. To date, no cure or effective treatments are available for RP.

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common cause of inherited blindness in adults. Mutations in the PRPF31 gene produce autosomal dominant RP (adRP). To date there are no effective treatments for this disease.

Striatal astrocytes act as a reservoir for L-DOPA.

L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astrocytes may influence their availability in the dopaminergic system of PD. To assess possible L-DOPA- and DA-uptake and metabolic properties of striatal astrocytes, we examined the expression of L-DOPA, DA and DAT in striatal astrocytes of hemi-parkinsonian model rats after repeated L-DOPA administration, and measured the contents of L-DOPA, DA and their metabolite in primary cultured striatal astrocytes after L-DOPA/DA treatment.

A Study into the Evolutionary Divergence of the Core Promoter Elements of and .

Mutations in have been implicated in retinitis pigmentosa, a blinding disease caused by degeneration of rod photoreceptors. The disease mechanism in the majority of cases is haploinsufficiency. Crucially, attempts at generation of animal models of disease have proved unsuccessful, yielding animals with a visual phenotype that does not mirror human disease.

Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.

Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson's disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine.

Study of cerebello-thalamocortical pathway by transcranial magnetic stimulation in Parkinson's disease.

Background: Although functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms.

Objective/hypothesis: We used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment.

Methods: We studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition-CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls.

ATR localizes to the photoreceptor connecting cilium and deficiency leads to severe photoreceptor degeneration in mice.

Ataxia-telangiectasia and Rad3 (ATR), a sensor of DNA damage, is associated with the regulation and control of cell division. ATR deficit is known to cause Seckel syndrome, characterized by severe proportionate short stature and microcephaly. We used a mouse model for Seckel disease to study the effect of ATR deficit on retinal development and function and we have found a new role for ATR, which is critical for the postnatal development of the photoreceptor (PR) layer in mouse retina.

Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT.

Lewy bodies containing the centrosomal protein γ-tubulin and fragmentation of Golgi apparatus (GA) have been described in nigral neurons of Parkinson's disease (PD) patients. However, the relevance of these features in PD pathophysiology remains unknown. We analyzed the impact of proteasome inhibition in the formation of γ-tubulin-containing aggregates as well as on GA structure.

Neuroprotective effects of zonisamide target astrocyte.

Objective: Recent double-blind, controlled trials in Japan showed that the antiepileptic agent zonisamide (ZNS) improves the cardinal symptoms of Parkinson's disease. Glutathione (GSH) exerts antioxidative activity through quenching reactive oxygen species and dopamine quinone. GSH depletion within dopaminergic neurons impairs mitochondrial complex I activity, followed by age-dependent nigrostriatal neurodegeneration.

Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease.

Purpose: To determine clinical predictors and accuracy of (123)I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD).

Methods: Several clinical features and (123)I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated.

Results: DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.