Schwann Cell-Mediated Preservation of Vision in Retinal Degenerative Diseases via the Reduction of Oxidative Stress: A Possible Mechanism

After central nervous system (CNS) injuries, the regeneration process does not work out well except for remyelination process. This remyelination capacity in CNS can be mentioned as a worthy example of stem/precursor cell-mediated renewal process. Remyelination in CNS is mediated by Schwann cells which act mainly as remyelinating agents in peripheral nervous system (PNS) but several studies have shown their potential role in CNS too. Schwann cells have the capacity of supporting and saving retinal cells by secreting growth factors like:  Brain-derived neurotrophic factor (BDNF), Glial cell-derived neurotrophic factor (GDNF), and Basic fibroblast growth factor (bFGF) in subretinal space. Retinal degenerative diseases are one of the most important debilitating concerns in modern countries which has encountered the problem of ageing population. One of the best examples of retinal degenerative disease which is a leading cause of permanent visual loss in Western world is age related macular degeneration (AMD). In United States it is believed that nearly 1.75 million, older than 40 years have end stages of this debilitating disease, and it is estimated that this number will progress to approximately 3 million people by year 2020. One of the most common pathways which is involved in initiation and development of retinal disease is called Oxidative stress. Schwann cells are capable of secreting high amounts of antioxidant enzymes which protect PNS in front of oxidative stress which is result of glucose fluctuation in diabetic patients. The antioxidant role of Schwann cells in PNS may be the possible mechanism which can make Schwann cells potent reconstructing agents in CNS and especially in retinal injuries and retinal degenerative disease

Schwann Cell-Mediated Preservation of Vision in Retinal Degenerative Diseases via the Reduction of Oxidative Stress: A Possible Mechanism

After central nervous system (CNS) injuries, the regeneration process does not work out well except for remyelination process. This remyelination capacity in CNS can be mentioned as a worthy example of stem/precursor cell-mediated renewal process. Remyelination in CNS is mediated by Schwann cells which act mainly as remyelinating agents in peripheral nervous system (PNS) but several studies have shown their potential role in CNS too. Schwann cells have the capacity of supporting and saving retinal cells by secreting growth factors like:  Brain-derived neurotrophic factor (BDNF), Glial cell-derived neurotrophic factor (GDNF), and Basic fibroblast growth factor (bFGF) in subretinal space. Retinal degenerative diseases are one of the most important debilitating concerns in modern countries which has encountered the problem of ageing population. One of the best examples of retinal degenerative disease which is a leading cause of permanent visual loss in Western world is age related macular degeneration (AMD). In United States it is believed that nearly 1.75 million, older than 40 years have end stages of this debilitating disease, and it is estimated that this number will progress to approximately 3 million people by year 2020. One of the most common pathways which is involved in initiation and development of retinal disease is called Oxidative stress. Schwann cells are capable of secreting high amounts of antioxidant enzymes which protect PNS in front of oxidative stress which is result of glucose fluctuation in diabetic patients. The antioxidant role of Schwann cells in PNS may be the possible mechanism which can make Schwann cells potent reconstructing agents in CNS and especially in retinal injuries and retinal degenerative disease

Narrative review-drug delivery in age-related macular degeneration

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration (AMD). AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7% of blindness worldwide. Advanced AMD can be classified into two subtypes: late-stage dry AMD [known as geographic atrophy (GA)] and neovascular AMD (nAMD). GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium. Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium (RPE) or retina, a process known as choroidal neovascularization (CNV). Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD. Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD. Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies. Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems, including hydrogels, microparticles, nanoparticles, implants, and liposomes. Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations. New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment

Role of Schwann Cells in Preservation of Retinal Tissue Through Reduction of Oxidative Stress

The aim of this study was to evaluate the effect of subretinal injection of Schwann cells on preservation of retina by decreasing oxidative stress in Dystrophic Royal College of Surgeons (RCS) rats. Schwann cells were harvested from the sciatic nerve of postnatal day 5, RCS rats. Twenty-five RCS rats randomly assigned to cell and sham groups. Schwann cells injected in the sub-retinal space in one eye of the cell group and carrier medium was injected in one eye of the sham group. The proof for the appropriate site of injection of Schwann cells confirmed by the green fluorescent protein (GFP) positive cells. Electroretinogram (ERG) and enucleation for histopathology and enzymatic evaluation were performed 1, 2 and 3 months post-injection. The enzymatic evaluation included catalase, superoxide dismutase (SOD) and glutathione peroxidase 1 (GPx1) by enzyme-linked immunosorbent assay (ELISA) method. Three months after injection, histopathology assessments showed a complete absence of the outer nuclear layer (ONL), photoreceptors and obvious reduction of retinal pigment epithelium (RPE) in the sham group. Cell group showed marked preservation of RPE, choroidal congestion and mild presence of ONL. The green fluorescent protein positive Schwann cells remained in one integrated layer during the study under RPE. The enzymatic evaluation showed that in cell group expression of SOD and GPx1 until month 2 and catalase until month 1 were significantly more than the sham group. At the end of month 3, the amplitude of ERG waves significantly preserved in cell group in comparison to baseline waves and the sham group. We concluded that Schwan cells are able to preserve retinal in RCS rats by reducing oxidative stress. Epub: October 1, 2019

Topographic correspondence of peripheral retinal lesions between the fellow eyes of patients with rhegmatogenous retinal detachment and retinal break

Background: In rhegmatogenous retinal detachment (RRD), the risk of fellow eye involvement varies from 5% to 34% according to the follow-up duration and criteria used for patient selection. The aim of the present study was to investigate the frequency, characteristics, and predisposing factors for symmetric lesions in the fellow eyes of patients with RRD or retinal breaks. Results: Of the 68 participants, with a mean (standard deviation) age of 48 (12.1) years, 54 (79.4%) were men, and 14 (20.6%) were women. Of the 68 primary eyes, 60 (88.2%) had RRDs, and eight (11.8%) had retinal breaks. Horseshoe tears were the main lesion in 41 (68.3 %) primary eyes with RRD. Symmetric lesions were observed in 37 (54.4%) fellow eyes, including retinal breaks in 16 (43.2%) and lattice degeneration without breaks in 21 (56.8%) eyes. Lattice degeneration and multiple breaks were observed in 15 of 28 (53.6%) primary eyes with a lattice, whereas only seven of 40 (17.5%) lattice-free primary eyes had multiple breaks (P = 0.002). A multiple logistic regression model revealed that the presence of lattice degeneration in the primary eye (odds ratio, 26.91; 95% confidence interval, 4.18 – 173.20; P < 0.001) was the only factor predicting symmetricity in the fellow eye. Conclusions: More than half of the patients with RRD or retinal breaks in the primary eye harbored symmetrical retinal lesions in their fellow eyes. This emphasizes the importance of regular examination of the fellow eyes with a greater focus on symmetric positions in the fellow eye. The presence of a lattice in the primary eye was the only predictor of symmetry in the contralateral eye. Further longitudinal studies with larger populations are required to determine the significance of these symmetric lesions in the fellow eyes of patients with RRD and the value of prophylactic treatment

Immortal plain gut sutures: A case report

Purpose: We report the case of a 79-year-old male who presented with irritation and foreign body sensation due to the subconjunctival plain gut sutures that did not dissolve three years after undergoing pars plana vitrectomy (PPV) for macular hole repair. Observation: A 79-year-old male presented with foreign body sensation and irritation in his left eye. On slit lamp examination, the source of the foreign body sensation was two apparently intact plain gut sutures were visible under the conjunctiva, nasal and temporal to the cornea. These plain gut sutures were placed at the conclusion of PPV surgery three years prior to presentation. After discussion, the patient elected suture removal, and two thin, translucent suture fragments were removed. Histopathologic evaluation revealed eosinophilic dense collagenous material with frayed edges, compatible with gut suture, associated with rare macrophages and scant fibrous tissue. Conclusion and importance: The sclerotomies created for PPV occasionally need to be sutured at the conclusion of surgery to ensure wound closure, to retain tamponade, or to reduce endophthalmitis risk. Plain gut sutures have been shown to cause less scleral inflammation and to improve patient comfort compared to Vicryl sutures. However, in this case the plain gut sutures had not dissolved three years after PPV and had caused discomfort for patient and needed to be removed

Utility of blood as the clinical specimen for the diagnosis of ocular toxoplasmosis using uracil DNA glycosylase-supplemented loop-mediated isothermal amplification and real-time polymerase chain reaction assays based on REP-529 sequence and B1 gene

Background: Ocular infection with Toxoplasma gondii is a major preventable cause of blindness, especially in young people. The aim of the present study was to assess detection rate of T. gondii DNA in blood samples of clinically diagnosed of ocular toxoplasmosis using uracil DNA glycosylase-supplemented loop-mediated isothermal amplification (UDG-LAMP) and real-time quantitative PCR (qPCR) based on REP-529 and B1. Methods: One hundred and seventeen patients with clinically diagnosed ocular toxoplasmosis (OT) were participated in the study as well as 200 control patients. Peripheral blood samples were assessed using UDG-LAMP and qPCR techniques targeting REP-529 and B1. Results: Detection limits of qPCR using REP-529 and B1 were estimated as 0.1 and 1 fg of T. gondii genomic DNA, respectively. The limits of detection for UDG-LAMP using REP-529 and B1 were 1 and 100 fg, respectively. In this study, 18 and 16 patients were positive in qPCR using REP-529 and B1, respectively. Based on the results of UDG-LAMP, 15 and 14 patients were positive using REP-529 and B1, respectively. Results of the study on patients with active ocular lesion showed that sensitivity of REP-529 and BI targets included 64 and 63%, respectively using qPCR. Sensitivity of 62 and 61%, were concluded from UDG-LAMP using REP-529 and B1 in the blood cases of active ocular lesion. qPCR was more sensitive than UDG-LAMP for the detection of Toxoplasma gondii DNA in peripheral blood samples of patients with clinically diagnosed toxoplasmic chorioretinitis. Furthermore, the REP-529 included a better detection rate for the diagnosis of ocular toxoplasmosis in blood samples, compared to that the B1 gene did. Moreover, the qPCR and UDG-LAMP specificity assessments have demonstrated no amplifications of DNAs extracted from other microorganisms based on REP-529 and B1. Conclusions: Data from the current study suggest that qPCR and UDG-LAMP based on the REP-529 are promising diagnostic methods for the diagnosis of ocular toxoplasmosis in blood samples of patients with active chorioretinal lesions

Cell-based therapies for retinal diseases: a review of clinical trials and direct to consumer cell therapy clinics

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt\u27s macular dystrophy have been published. However, there have also been numerous reports of complications from unproven cell therapy treatments marketed by cell therapy clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside of legitimate studies are presented. Main body: Cell-based therapies can be applied to disorders that involve the RPE via a variety of techniques. A defining characteristic of any cell therapy treatment is the cell source used: human embryonic stem cells, induced pluripotent stem cells, and human umbilical tissue-derived cells have all been studied in published trials. In addition to the cell source, various trials have evaluated particular immunosuppression regiments, surgical approaches, and outcome measures. Data from early phase studies investigating cell-based therapies in non-neovascular age-related macular degeneration (70 patients, five trials), neovascular age-related macular degeneration (12 patients, four trials), and Stargardt\u27s macular dystrophy (23 patients, three trials) have demonstrated safety related to the cell therapies, though evidence of significant efficacy has not been reported. This is in contrast to the multiple reports of serious complications and permanent vision loss in patients treated at cell therapy clinics. These interventions are marketed directly to patients, funded by the patient, lack Food and Drug Administration approval, and lack significant oversight. Conclusion: Currently, there are no proven effective cell-based treatments for retinal diseases, although several trials have investigated potential therapies. These studies reported favorable safety profiles with multiple surgical approaches, with cells derived from multiple sources, and with utilized different immunosuppressive regiments. However, data demonstrating the efficacy and long-term safety are still pending. Nevertheless, cell therapy clinics continue to conduct direct-to consumer marketing for non-FDA-approved treatments with potentially blinding complications

Accuracy and Utility of Internet Image Search as a Learning Tool for Retinal Pathology

Purpose Ophthalmology residency training heavily relies on visual and pattern recognition-based learning. In parallel with traditional reference texts, online internet search via Google Image Search (GIS) is commonly used and offers an accessible fund of reference images for ophthalmology trainees seeking rapid exposure to images of retinal pathology. However, the accuracy and quality of this tool within this context is unknown. We aim to evaluate the accuracy and quality of GIS images of selected retinal pathologies. Methods A cross-sectional study was performed of GIS of 15 common and 15 rare retinal diseases drawn from the American Academy of Ophthalmology residency textbook series. A total of 300 evaluable image results were assessed for accuracy of images and image source accountability in consultation with a vitreoretinal surgeon. Results A total of 377 images were reviewed with 77 excluded prior to final analysis. A total of 288 (96%) search results accurately portrayed the retinal disease being searched, whereas 12 (4%) were of an erroneous diagnosis. More images of common retinal diseases were from patient education Web sites than were images of rare diseases (p < 0.01). Significantly more images of rare retinal diseases were found in peer-reviewed sources (p = 0.01). Conclusions GIS search results yielded a modest level of accuracy for the purposes of ophthalmic education. Despite the ease and rapidity of accessing multimodal retinal imaging examples, this tool may best be suited as a supplementary resource for learning among residents due to limited accuracy, lack of sufficient supporting information, and the source Web site's focus on patient education

Changes in Leukocyte Subpopulations with Decline in Glomerular Filtration Rate in Patients with Type 2 Diabetes

Recent studies suggested the role of white blood cells (WBCs) in the pathogenesis and complications of type 2 diabetes. Increased WBC counts predict mortality in patients with chronic kidney disease (CKD). In this study alterations in WBC subpopulations in diabetic patients with non-dialysis dependent CKD are investigated. This was a cross-sectional study  on 376 participants, including   272 diabetic  patients  and  104  healthy  controls.  Total  and  differential  WBC  counts  were  compared  among diabetics with CKD, diabetics without CKD and controls. Among patients with type 2 diabetes, there was no significant difference in total WBC count between those with and without CKD. Diabetic patients with CKD had higher neutrophil, monocyte and eosinophil and lower lymphocyte count compared with both diabetic patients without CKD and healthy controls. Except for monocytes, a significant association was observed between GFR and differential WBC counts, which persisted after adjustment for conventional diabetes riskfactors (R2=0.272, P < 0.001 for regression model). Neutrophil/lymphocyte ratio was the best predictor ofGFR in total study population (beta= -1.995 ± 0.45,