Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Autoantibodies detection in patients affected by autoimmune retinopathies.

OBJECTIVE: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. PATIENTS AND METHODS: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. RESULTS: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). CONCLUSIONS: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Bioetics Issues of Artificial Placenta and Artificial Womb Technology.

Abstract: The worldwide infertility crisis and the increase in mortality and morbidity among infants, due to preterm births and associated complications, have stimulated research into artificial placenta (AP) and artificial womb (AW) technology as novel solutions. These technologies mimic the natural environment provided in the mother's womb, using chambers that ensure the supply of nutrients to the fetus and disposal of waste substances through an appropriate mechanism. This review aims to highlight the background of AP and AW technologies, revisit their historical development and proposed applications, and discuss challenges and bioethical and moral issues. Further research is required to investigate any negative effects of these new technologies, and ethical concerns pertaining to the structure and operation of this newly developed technology must be addressed and resolved prior to its introduction to the public sphere.

In Memory of Professor Derek Pheby.

Abstract: Professor Derek Pheby's passing in November 2022 marked a profound loss for the scientific community. Professor Derek Pheby, a stalwart figure in the fields of autoimmune diseases and bioethics, was known for his dedication to scientific research and patients' support, particularly for those affected by paraneoplastic autoimmune syndromes. Professor Pheby made significant contributions to research, especially about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). His leadership of the ME Biobank and scientific coordination of EUROMENE demonstrated his commitment to pushing boundaries and fostering international collaborations. Professor Pheby's scientific work addressed various aspects of ME/CFS, from physician education to patient needs, the development of a post-mortem tissue bank, and effective treatments. Beyond his medical career, Professor Pheby was a crucial member of the Independent Ethics Committee of MAGI, he was a poet, humanitarian, and advocate for child protection. His generosity and boundless spirit left an enduring legacy, fostering innovative research in the pursuit of combating autoimmune diseases.

Human Cloning: Biology, Ethics, and Social Implications.

Abstract: This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal implications. The exposition commences with a succinct historical and contextual overview of human cloning, segueing into an in-depth exploration of its biological intri-cacies. Central to this biological scrutiny is a comprehensive analysis of somatic cell nuclear transfer (SCNT) and its assorted iterations. The accomplishments and discoveries in cloning technology, such as successful animal cloning operations and advances in the efficiency and viability of cloned embryos, are reviewed. Future improvements, such as reprogramming procedures and gene editing technology, are also discussed. The discourse extends to ethical quandaries intrinsic to human cloning, entailing an extensive contemplation of values such as human dignity, autonomy, and safety. Furthermore, the ramifications of human cloning on a societal plane are subjected to scrutiny, with a dedicated emphasis on ramifications encompassing personal identity, kinship connections, and the fundamental notion of maternity. Culminating the analysis is a reiteration of the imperative to develop and govern human cloning technology judiciously and conscientiously. Finally, it discusses several ethical and practical issues, such as safety concerns, the possibility of exploitation, and the erosion of human dignity, and emphasizes the significance of carefully considering these issues.

Neurofibromatosis type 1-associated optic pathway gliomas: pathogenesis and emerging treatments.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder associated with an increased risk of developing a variety of benign and malignant tumors. Fifteen to 20% of children with NF1 are diagnosed with an optic pathway glioma (NF1-OPG) before 7 years of age, and more than half of them experience visual decline. At present, no effective therapy is available for prevention, restoration, or even stabilization of vision loss in subjects affected by NF1-OPG. This paper aims to review the main emerging pharmacological approaches that have been recently assessed in preclinical and clinical settings. We performed a search of the literature using Embase, PubMed, and Scopus databases to identify articles regarding NF1-OPGs and their treatment up to July 1st, 2022. The reference lists of the analyzed articles were also considered a source of literature information. To search and analyze all relevant English articles, the following keywords were used in various combinations: neurofibromatosis type 1, optic pathway glioma, chemotherapy, precision medicine, MEK inhibitors, VEGF, nerve growth factor. Over the past decade, basic research and the development of genetically engineered mice models of NF1-associated OPG have shed light on the cellular and molecular mechanisms underlying the disease and inspired animal and human testing of several compounds. A promising line of research is focusing on the inhibition of mTOR, a protein kinase controlling proliferation, protein synthesis rate and cell motility that is highly expressed in neoplastic cells. Several mTOR blockers have been tested in clinical trials, the most recent of which employed oral everolimus with encouraging results. A different strategy aims at restoring cAMP levels in neoplastic astrocytes and non-neoplastic neurons, since reduced intracellular cAMP levels contribute to OPG growth and, more importantly, are the major determinant of NF1-OPG-associated visual decline. So far, however, this approach has only been attempted in preclinical studies. Stroma-directed molecular therapies - seeking to target Nf1 heterozygous brain microglia and retinal ganglion cells (RGCs) - are another fascinating field. Microglia-inhibiting strategies have not yet reached clinical trials, but preclinical studies conducted over the last 15 years have provided convincing clues of their potential. The importance of NF1-mutant RGCs in the formation and progression of OPGs also holds promise for clinical translation. The evidence of Vascular Endothelial Growth Factor (VEGF)- Vascular Endothelial Growth Factor (VEGFR) signaling hyperactivity in pediatric low-grade gliomas prompted the use of bevacizumab, an anti-VEGF monoclonal antibody, which was tested in children with low-grade gliomas or OPGs with good clinical results. Neuroprotective agents have also been proposed to preserve and restore RGCs and topical eye administration of nerve growth factor (NGF) has demonstrated encouraging electrophysiological and clinical results in a double-blind, placebo-controlled study. Traditional chemotherapy in patients with NF1-OPGs does not significantly ameliorate visual function, and its effectiveness in halting tumor growth cannot be considered a satisfactory result. Newer lines of research should be pursued with the goal of stabilizing or improving the vision, rather than reducing tumor volume. The growing understanding of the unique cellular and molecular characteristics of NF1-OPG, coupled with the recent publication of promising clinical studies, raise hope for a shift towards precision medicine and targeted therapies as a first-line treatment.

In vitro cell culture of amniotic fluid keratinocytes on amniotic membrane: the ideal tissue for repairing skin ulcers.

OBJECTIVE: The amniotic fluid contains a large population of stem keratinocytes demonstrating minimal immunological rejection. Recent evidence suggests that stem cells from the amniotic fluid can be employed in the field of tissue engineering. In this work we identified precursors of the epithelial cells and expanded them in vitro. MATERIALS AND METHODS: After collecting samples of amniotic fluid and separating the cells via centrifugation, we seeded a portion of these cells in selection media to analyze the proliferation of epithelial cells. The stem cells precursors of keratinocytes were identified through specific markers. The expression of these markers was evaluated by immunofluorescence and reverse transcription polymerase chain reaction (PCR). RESULTS: The stem cells demonstrated 90% confluence, after undergoing proliferation in the selection medium for 15 days. Most of these cells tested positive for the keratinocyte-specific markers, but negative for stem cell specific markers. Of note, the identity of the keratinocytes was well established even after several subcultures. CONCLUSIONS: These results suggested that it is feasible to isolate and expand differentiated cell populations in the amniotic fluid from precursor cells. Furthermore, amniotic membranes can be utilized as scaffolds to grow keratinocytes, which can be potentially exploited in areas of skin ulcer transplantation and tissue engineering interventions.

PERG adaptation for detection of retinal ganglion cell dysfunction in glaucoma: a pilot diagnostic accuracy study.

It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-min presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls. In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects. PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01), whereas phase angular dispersion was greater in patients but not significantly different between the two groups. The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude, and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase, respectively. The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional retinal ganglion cell autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.

Taste, olfactory and texture related genes and food choices: implications on health status.

OBJECTIVE: The food choices are due to a mixture of sensory signals including gustatory, olfactory, and texture sensations. The aim of this quality review was to update data about studies concerning genetics of taste, olfactory and texture receptors and their influence on the health status in humans. MATERIALS AND METHODS: An electronic search was conducted in MEDLINE, Pubmed database and Scopus, for articles published in English until December 2018. Two independent researches selected the studies and extracted the data. RESULTS: The review confirms the importance of inter-individual variations in taste, olfactory and texture related genes on food choices and their implications in the susceptibility to nutrition-related conditions such as obesity, dental caries, diabetes, cardiovascular disease, hypertension, hyperlipidemia and cancer. CONCLUSIONS: The knowledge of variants in taste, olfactory and texture related genes can contribute to the prevention of diseases related to unhealthy nutrition. Further studies would be useful to identify other variants in the genes involved in these systems.

The value of multifocal electroretinography to predict progressive visual acuity loss in early AMD.

BACKGROUND: To investigate, in a prospective study, the role of multifocal electroretinography (mfERG) for predicting visual acuity decline in early age-related macular degeneration (AMD) with time. METHODS: Twenty-six early AMD patients (12 males and 14 females, mean age 66.9 ± 9.8; range 46-82 years) were included in the study. A complete ophthalmic examination and mfERG (Retiscan, Roland Germany, ISCEV standard protocol) were performed at the study entry (baseline), after 20 and 24 months. The first-order kernel mfERG responses were analyzed by ring analysis. The amplitude density (AD) of the first positive peak (P1, nV/deg(2)), the P1 amplitude (µV) and P1 implicit time (ms) for Rings 1 (central) to 6 (most peripheral) were evaluated. Data were statistically analyzed by analysis of variance and receiver operating characteristic (ROC) curves. RESULTS: The loss in the mfERG Ring 1 AD from normal control values, recorded at baseline, was correlated with the decrease in ETDRS visual acuity with time (P = 0.004). ROC analysis showed that, after 24 months, the average decline in visual acuity was greater (3 letters vs 0.4 letters, P = 0.0021) in patients whose Ring 1 P1 AD at baseline was equal to or less than 65.9 nV/deg(2), compared to those with higher AD values. Both P1 amplitude and AD of Ring 1 had an area under the curve of 0.702 (95% confidence interval 0.50-0.92) with a sensitivity of 64.3% (35.14-87.24%) and a specificity of 91.7% (61.52-99.79%). CONCLUSIONS: The present results indicate that mfERG P1 amplitude and AD of Ring 1 may be highly specific to predict visual acuity decline in early AMD.

A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function.

Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. Design. Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology setting. Participants. Twenty-nine early AMD patients (age range: 55-85 years) with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation (20 mg/day) over an average period of treatment of 14 (±2) months. Measurements. Clinical examination and focal-electroretinogram-(fERG-) derived macular (18°) flicker sensitivity estimate (Falsini et al. (2010)) every three months over a followup of 14 (±2) months. Retinal sensitivity, the reciprocal value of the estimated fERG amplitude threshold, was the main outcome measure. Results. After three months of supplementation, mean fERG sensitivity improved by 0.3 log units compared to baseline values (P < 0.01), and mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P < 0.01). These changes remained stable over the follow-up period. Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup.

[Clinic use of Laser Doppler Flowmetry (LDF) in the study of subfoveal choroidal circulation]. / Impiego clinico del Laser Doppler Flussometria (LDF) nello studio della circolazione coroideale sottofoveale.

Today our knowledge of the choroidal circulation is limited: we know its anatomy, but, on the other hand, its physiopathology remains to be fully. The choroid is involved in a number of important ocular diseases. The Laser Doppler Flowmetry (LDF) is a technique that allows non-invasive measurement of haemodynamic parameters of the subfoveal choroidal circulation. It is easy to use in daily clinic activity. The aim of this mini-review is to describe LDF studies of the choroidal circulation performed in healthy subjects under different environmental conditions, in subjects with ocular diseases, as well as studies of the effects of various drugs can induce on this circulation.

The effects of hypoxia on the ERG in paediatric cerebral malaria.

BACKGROUND/AIMS: Cerebral malaria (CM) is a disease of high mortality worldwide. It can be associated with malarial retinopathy (MR) resulting from impaired perfusion within the retinal microvasculature. Areas of capillary non-perfusion (CNP) appear white (retinal whitening) on ophthalmoloscopy. In this study, electrophysiological investigations were performed to investigate the physiological consequences of these hypoxic and ischaemic changes. METHODS: Children admitted with CM were assessed for inclusion in the study. Those with MR underwent further detailed fundus assessment to quantify retinal whitening and were then designated a severity score. Electrophysiological recordings were performed using a miniganzfeldt stimulator with calibration to the International Society for Clinical Electrophysiology of Visual (ISCEV) standards. ERG data were then analysed with respect to presence of MR and also graded disease severity. RESULTS: Thirty-one children were recruited with a diagnosis of CM, 20 had MR (group 1), and 11 had absent MR (group 2). Statistical analyses of these two groups showed a significant relationship between reduced single flash cone b wave amplitude (CBWA) and increased severity of retinal whitening/CNP (P<0.05). Cone and maximal response b : a wave ratios remained >1 in all subjects. CONCLUSION: Retinal whitening/CNP in MR is associated with significant changes in ERG cone b wave function. The relatively high b : a ratio is compatible with the high frequency of MR resolution without sequelae.

Cytidine-5'-diphosphocholine (Citicoline): a pilot study in patients with non-arteritic ischaemic optic neuropathy.

BACKGROUND AND PURPOSE: Our work evaluates visual function before and after treatment with cytidine-5-diphosphocholine (Citicoline) in patients with non-arteritic ischaemic optic neuropathy (NION). METHODS: Twenty-six patients in which at least 6 months elapsed from NION, were randomly divided into two age-similar groups: 14 patients had Citicoline (Cebrolux-Tubilux, Italy, 1600 mg/diem for 60 days, followed by a 120-day period of wash out, days 60-180) (T-NION); 12 patients had no treatment during the same period (NT-NION). At day 180, in T-NION a second period of treatment (days 181-240) followed by a wash-out (days 241-360) was performed. Fourteen age-matched healthy subjects provided normative data. In all patients, pattern-electroretinogram (PERG), visual evoked potentials (VEPs) and visual acuity (VA) measurements were performed at baseline and at days 60 and 180. In T-NION, further measurements were achieved at days 240 and 360. RESULTS: At baseline, NT-NION and T-NION patients showed abnormal PERGs and VEPs, and reduced VA, compared to controls. At the end of treatment (days 60 and 240), T-NION patients showed improvement (P < 0.01) of PERGs, VEPs parameters and VA, compared to pre-treatment values. After wash out, functional improvements persisted compared to baseline. No changes in NT-NION patients were observed. CONCLUSIONS: Our results suggest a beneficial effect of oral Citicoline in NION.

Optical coherence tomography and focal electroretinogram evaluation of cystoid macular edema secondary to retinitis pigmentosa treated with intravitreal triamcinolone: case report.

PURPOSE: To assess macular structure and function by optical coherence tomography (OCT) and focal electroretinogram (FERG) before and after intravitreal triamcinolone acetonide (IVTA) administration for cystoid macular edema (CME) in a patient with retinitis pigmentosa (RP). METHODS: A 33-year-old man with RP and refractory bilateral macular edema was treated with IVTA in his left eye and evaluated with visual acuity, OCT, and FERG for 6 months. RESULTS. Compared to the fellow eye, after IVTA mean retinal thickness significantly decreased, while FERG amplitude and phase did not show significant changes at the end of follow-up. Visual acuity showed a significant tendency to improve. CONCLUSIONS: In this case report, IVTA improved macular anatomy and visual acuity; this result, however, was not associated with a similar electrophysiologic response.

Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families.

Retinitis pigmentosa is the most common form of retinal degeneration and is heterogeneous both clinically and genetically. The autosomal dominant forms (ADRP) can be caused by mutations in 12 different genes. This report describes the first simultaneous mutation analysis of all the known ADRP genes in the same population, represented by 43 Italian families. This analysis allowed the identification of causative mutations in 12 of the families (28% of the total). Seven different mutations were identified, two of which are novel (458delC and 6901C-->T (P2301S), in the CRX and PRPF8 genes, respectively). Several novel polymorphisms leading to amino acid changes in the FSCN2, NRL, IMPDH1, and RP1 genes were also identified. Analysis of gene prevalences indicates that the relative involvement of the RHO and the RDS genes in the pathogenesis of ADRP is less in Italy than in US and UK populations. As causative mutations were not found in over 70% of the families analysed, this study suggests the presence of further novel genes or sequence elements involved in the pathogenesis of ADRP.

[Diet and management of degenerative diseases of the retina (retinitis pigmentosa)]. / Dieta e Vitamina A nel trattamento di forme "sensibili" di retinite pigmentosa.

Considerable progress has been made in the understanding and management of degenerative diseases of the retina. The dietetic intervention has been favourably proposed in the most common forms of retinitis pigmentosa, a condition potentially leading to blindness. Vitamin A has been shown to be effective in delaying progression of the disease. In these patients such treatment is the only possible therapy, to date, and a lifetime generous supplementation of retinol is advisable, together with a vitamin A-rich diet and/or a dietary supplement (e.g. carrot flour) or pharmacologic supplement of vitamin A. Supply of vitamin A in doses up to 25000 IU (7500 igr/day), even for several years, has so far proved safe from risk of occurrence of liver disease. A possible effect on hypercholesterolemia related to a very prolonged treatment in predisposed individuals can be avoided by using a special diet, particularly enriched with beta-carotene. Guidelines for preparing a diet, specially formulated to provide an elevated weekly supply of vitamin and/or its precursor (equal to 15000 IU or 5000 microg of RE, retinol equivalent) and to control possible risk factors related to dietetic manipulation (supply of fat lower than 30% of total calories, variable levels of cholesterol and polyunsaturated fatty acids n-3, n-6) are presented. As long as resolutive therapy is lacking, dietetic intervention plays a primary role, although underestimated, in the management of the patients suffering from retinitis pigmentosa. The diet is specifically characterized by presence of food with a high content of carotenoids, substances with a favourable and additive effect.

Functionally rodless mice: transgenic models for the investigation of cone function in retinal disease and therapy.

Two genetically engineered strains of mice were used to characterize murine cone function electroretinographically, without interference of rod-driven responses: (1) mice with a deletion of the gene for the rod transducin alpha-subunit (transducin alpha-/-), and (2) mice with rod arrestin deleted (arrestin -/-). In the first three months of age, both strains have a normal complement of rods and normal rod structure, but transducin alpha-/- mice have no rod-driven responses to light, while rod-driven activity of arrestin -/- mice can be suppressed by a single intense flash for hours. In response to intense flashes the electroretinograms of these strains of mice showed a readily identifiable, pure-cone a-wave of approximately 10 microV saturating amplitude. A 530 nm background that saturates rod responses of wild type mice was found to desensitize the b-wave responses of mice of both transgenic lines, whether the b-waves were driven by photons captured by M- or UV-cone pigments. The desensitizing effect of the 530 nm background on UV-pigment driven responses provides new evidence in support of the hypothesis of functional co-expression of the M-pigment in cones expressing primarily the UV-pigment.