Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration

Background: Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation (AFT) efficacy was demonstrated by several studies, since these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose derived stem-cells (ADSCs) in tissue adipose’s stromal vascular fractions (SVF), and platelet rich plasma (PRP). Methods: Twelve eyes in 12 dry age macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using: best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera by means of the variant second Limoli, grafting of mature fat cells and ADSCs in SVF enriched with PRP (LRRT). In order to test if the differences pre- and post-treatment were significant the Wilcoxon signed rank test has been performed. Results: Adverse effects were not reported in the patients. After surgery with LRRT the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 μVolts (µV) with an average increase of 47.44% highly significant (p<0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 μV with an average increase of 15.56% (p<0.1). Conclusions: Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies

Visual field improvement in non-arteritic posterior ischemic optic neuropathy in a patient treated with intravenous prostaglandin E1 and steroids

Non-arteritic posterior ischemic optic neuropathy (NA-PION) is a disorder of reduced blood flow to the retrobulbar optic nerve. There is usually an acute loss of visual acuity and field. Previous studies have noted an improvement in visual acuity and in ocular and retrobulbar blood flow with the use of a potent vasodilator of the microcirculation, prostaglandin E1 (PGE1), and steroids. The current report describes immediate improvement in the visual fields and visual acuity in a patient with NA-PION treated with intravenous PGE1 and steroids 66 hours after onset. An 89-year-old white female was first seen in December 2016 with a sudden loss of vision in the right eye. After a complete eye exam and visual fields, the patient was diagnosed with NA-PION. Treatment was immediately started with steroids and intravenous PGE1. This was repeated once again the next morning. Visual acuity in the right eye improved from 1/10 + 1 to 7/10 + 3 at 5 days. The mean deviation of the visual field improved from – 7.10 decibels (dB) with a central scotoma of – 22 dB to – 2.97 dB with a central scotoma of – 19 dB. After 2 weeks, her visual acuity was 7/10 + 1 and visual field testing of the right eye revealed a mean deviation of – 2.54 dB with a central scotoma of – 9 dB. The left eye was unchanged. In cases of NA-PION, PGE1 and steroids should be considered to immediately restore blood flow to help improve visual acuity and visual fields

Antioxidant and biological properties of mesenchymal cells used for therapy in retinitis pigmentosa

Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenges in the field of ophthalmological research. Although this inherited retinal dystrophy is still an incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidence regarding the effectiveness of cell therapies in RP, especially those based on mesenchymal cells, and we focus on their therapeutic action: limitation of both oxidative stress and apoptotic processes triggered by the disease and promotion of cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP

Therapeutic approaches with intravitreal injections in geographic atrophy secondary to age-related macular degeneration: current drugs and potential molecules

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy

Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects

Purpose: To assess whether treatment with the Limoli Retinal Restoration Technique (LRRT) can be performed in patients with retinitis pigmentosa (RP), grafting the autologous cells in a deep scleral pocket above the choroid of each eye to exert their beneficial effect on the residual retinal cells. Methods: The patients were subjected to a complete ophthalmological examination, including best corrected visual acuity (BCVA), close-up visus measurements, spectral domain-optical coherence tomography (SD-OCT), microperimetry (MY), and electroretinography (ERG). Furthermore, the complete ophthalmological examination was carried out at baseline (T0) and at 6 months (T180) after surgery. The Shapiro-Wilk test was used to assess the normality of distribution of the investigated parameters. A mixed linear regression model was used to analyse the difference in all the studied parameters at T0 and T180, and to compare the mean change between the two groups. All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Results: LRRT treatment was performed in 34 eyes of 25 RP patients recruited for the study. The eyes were classified in two groups on the basis of foveal thickness (FT) assessed by SD-OCT: 14 eyes in Group A (FT≤190μm) and the remaining 20 ones in Group B (FT > 190μm). Although it had not reached the statistical significance, Group B showed a better improvement in BCVA, residual close-up visus and sensitivity than Group A. Conclusions: Previous studies have described the role of LRRT in slowing down retinal degenerative diseases. Consequently, this surgical procedure could improve the clinical and rehabilitative prognostic parameters in RP patients. On the other hand, further clinical research and studies with longer follow-up will be needed to evaluate its efficacy

UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions

Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the different photolabilities of their C–I and C–Br bonds. Although singlet oxygen is involved in photolesion formation, DNA SBrdU and SIdU photoactivation does not detectably increase DNA 8-oxoguanine levels. The absence of significant collateral damage to normal guanine suggests that UVA activation of DNA SIdU or SBrdU might offer a strategy to target hyperproliferative skin conditions that avoids the extensive formation of a known mutagenic DNA lesion

The type IV pilus chemoreceptor PilJ controls chemotaxis of one bacterial species towards another

Bacteria live in social communities, where the ability to sense and respond to interspecies and environmental signals is critical for survival. We previously showed the pathogen Pseudomonas aeruginosa detects secreted peptides from bacterial competitors and navigates through interspecies signal gradients using pilus-based motility. Yet, it was unknown whether P. aeruginosa utilizes a designated chemosensory system for this behavior. Here, we performed a systematic genetic analysis of a putative pilus chemosensory system, followed by high- speed live imaging and single cell tracking, to reveal behaviors of mutants that retain motility, but are blind to interspecies signals. The enzymes predicted to methylate (PilK) and demethylate (ChpB) the putative pilus chemoreceptor, PilJ, are necessary for cells to control the direction of migration. While these findings implicate PilJ as a bona fide chemoreceptor, such function had yet to be experimentally defined, as full-length PilJ is essential for motility. Thus, we constructed systematic genetic modifications of PilJ and found that without the predicted ligand binding domains or predicted methylation sites, cells lose the ability to detect competitor gradients, despite retaining pilus-mediated motility. Chemotaxis trajectory analysis revealed that increased probability and size of P. aeruginosa pilus-mediated steps towards S. aureus peptides, versus steps away, determines motility bias in wildtype cells. However, PilJ mutants blind to interspecies signals take less frequent steps towards S. aureus or steps of equal size towards and away. Collectively, this work uncovers the chemosensory nature of PilJ, provides insight into how cell movements are biased during pilus-based chemotaxis and identifies chemotactic interactions necessary for bacterial survival in polymicrobial communities, revealing putative pathways where therapeutic intervention might disrupt bacterial communication

Quantifying Cognitive Decrements Caused by Cranial Radiotherapy

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For many patients afflicted with CNS and non-CNS malignancies, radiotherapy and chemotherapy offer the best options for disease control. These treatments however come at a cost, and nearly all cancer survivors (~11 million in the US alone as of 2006) incur some risk for developing cognitive dysfunction, with the most severe cases found in patients subjected to cranial radiotherapy (~200,000/yr) for the control of primary and metastatic brain tumors1. Particularly problematic are pediatric cases, whose long-term survival plagued with marked cognitive decrements results in significant socioeconomic burdens2. To date, there are still no satisfactory solutions to this significant clinical problem