Development and Optimization of Freeze-Dried Eye Drops Derived from Plasma Rich in Growth Factors Technology

Purpose: To investigate whether plasma rich in growth factors (PRGF) eye drops maintain their biological potential after a freeze drying process. The addition of a lyopro-tectant like trehalose was also evaluated. Methods: Blood from three healthy donors was collected to obtain eye drops by PRGF technology. The resultant eye drops were divided in four groups: PRGF, freeze-dried PRGF (PRGF lyo), and PRGF lyophilized mixed with 2,5% trehalose (PRGF lyo+2.5T) or 5% trehalose (PRGF lyof+5T). Chemical and biological characteristics were evaluated. Photorefractive keratectomy was performed on C57BL/6 mice which were divided in three treatment groups: control, PRGF, and PRGF lyo. Corneal wound healing and haze formationwere evaluated macroscopically. Eyeswere collected at 1, 2, 3, and 7 days after surgery, and were processed for histologic studies. Results: The pH values of PRGF samples increased significantly after the lyophilization process. Osmolarity levels increased significantly in PRGF samplesmixed with trehalose in comparison with PRGF samples without protectants. The freeze drying process maintained growth factors levels as well as the biological properties of PRGF eye drops even without the use of lyoprotectants. PRGF lyo treatment significantly decreased the re-epithelialization time and haze formation in photorefractive keratectomy-treated corneas regarding PRGF and control groups. Furthermore, the PRGF lyo group significantly decreased the number of smooth muscle actin-positive cells in comparison with the control group at each time of the study and at days 2 and 3 in the PRGF group. Conclusions: The freeze drying process preserves the protein and growth factor content as well as the biological properties of PRGF eye drops, even without the use of protectants. Freeze-dried PRGF eye drops accelerate corneal tissue regeneration after photorefractive keratectomy in comparison with the control group. Translational Relevance: Our study shows the feasibility to preserve the biological capability of PRGF eye drops as freeze-dried formulation, avoiding the addition of protectants.This study received funding from the Basque Country Government, within the Elkartek program, phase I. Support program for collaborative research in strategic area, within the project named SINET (reference KK-2018/00048

Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy

Dry eye syndrome is a complex and insidious pathology with a high level of prevalence among the human population and with a consequently high impact on quality of life and economic cost. Currently, its treatment is symptomatic, mainly based on the control of lubrication and inflammation, with significant limitations. Therefore, the latest research is focused on the development of new biological strategies, with the aim of regenerating affected tissues, or at least restricting the progression of the disease, reducing scar tissue, and maintaining corneal transparency. Therapies range from growth factors and cytokines to the use of different cell sources, in particular mesenchymal stem cells, due to their multipotentiality, trophic, and immunomodulatory properties. We will review the state of the art and the latest advances and results of these promising treatments in this pathology

Assessing the brain through the eye: New ways to explore hepatic encephalopathy

Minimal hepatic encephalopathy (mHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments in mHE. We studied one of its precipitating factors, portal hypertension which is driving the inflammatory process behind mHE. The purpose was to describe an indirect diagnostic method able to detect the pathology at early stages based on the study of the vascularization and mast cells conjunctival hyperplasia as secondary inflammatory response associated to portal hypertension. Finally, we correlated the presence of histological changes in the eye in mHE with deficits in behavioral task acquisition.Rats were trained on a stimulus-response task and a spatial working memory task using the Morris water maze. Two groups of animals were used: a SHAM (sham-operated) group (n=10) and a portal hypertension (HT) group (n=10). The triple portal vein ligation method was used to create an animal model of mHE. Latencies to reach the platform, number of glial fibrillary acidic protein-immunoreactive astrocytes (GFAP-IR), mast cell expression and presence/absence of blood and lymphatic vessels were examined.There were differences in stimulus-response behavioral performance, with a deficit in the acquisition in the HT group. However, no differences between groups were found on the spatial working memory task. At the same time, differences between groups were found in the GFAP-IR density, which was lower in the HT group, and in the number of mast cells and the presence of vessels, which were higher in the HT group.In this study, we provide the first preliminary insight into the validity of exploring the eye as a possible tool to assess the diagnosis of mHE conditions

Anatomía radiológica y realidad aumentada: metodología basada en la ludificación para su aprendizaje

[ES] En los últimos años, la ludificación en el aula ha pasado de ser usada exclusivamente en el ámbito escolar hast a llegar a la universidad. El presente trabajo muestra y compara una experiencia de ludificación llevada a cabo en alumnado perteneciente tanto a Educación Superior universitaria como no universitaria. Se trata de un juego tipo quizz basado en casos clínicos reales de Radiología y Anatomía Radiológica, en los que el estudiante va avanzando a medida que acierta la respuesta mostrada a través de realidad aumentada. Tras el juego, se analizaron los conocimientos teórico-prácticos adquiridos y se observaron mejoras estadísticamente significativas. Por último, las encuestas de satisfacción indican que ambos perfiles de alumnado prefieren usar herramientas de ludificación en su aprendizaje y en el desarrollo de sus competencias.[EN] In recent years, gamification in the classroom has gone from being used primarily in the school environments to also being used at universities. The present work shows and compares a gamification experience carried out in students belonging to both higher education and non-university higher education. It is a questionnaire-type game based on real clinical cases of Radiology and Radiological Anatomy, in which the student advances as the answer shown through augmented reality is correct. After playing, the theoretical-practical knowledge acquired will be analyzed and statistically significant improvements will be observed. Finally, satisfaction surveys indicate that both student profiles prefer to use gamification tools in their learning and the development of their skills.Dugnol Menéndez, J.; Jiménez Arberas, E.; Ruiz Fernandez, M.; Fernández Valera, D.; Merayo-Lloves, J. (2021). Anatomía radiológica y realidad aumentada: metodología basada en la ludificación para su aprendizaje. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 128-141. https://doi.org/10.4995/INRED2020.2020.11935OCS12814

Differential profile of protein expression on human keratocytes treated with autologous serum and plasma rich in growth factors (PRGF)

Purpose The main objective of this study is to compare the protein expression of human keratocytes treated with Plasma rich in growth factors (PRGF) or autologous serum (AS) and previously induced to myofibroblast by TGF-beta 1 treatment. Methods Blood from healthy donor was collected and processed to obtain AS and PRGF eye drops. Blood derivates were aliquoted and stored at-80 degrees C until use. Keratocyte cells were pretreated for 60 minutes with 2.5 ng/ml TGF-beta 1. After that, cells were treated with PRGF, AS or with TGF-beta 1 (control). To characterize the proteins deregulated after PRGF and AS treatment, a proteomic approach that combines 1D-SDS-PAGE approach followed by LC-MS/MS was carried out. Results Results show a catalogue of key proteins in close contact with a myofibroblastic differentiated phenotype in AS treated-cells, whereas PRGF-treated cells show attenuation on this phenotype. The number of proteins downregulated after PRGF treatment or upregulated in AS-treated cells suggest a close relationship between AS-treated cells and cytoskeletal functions. On the other hand, proteins upregulated after PRGF-treatment or downregulated in AS-treated cells reveal a greater association with processes such as protein synthesis, proliferation and cellular motility. Conclusion This proteomic analysis helps to understand the molecular events underlying AS and PRGF-driven tissue regeneration processes, providing new evidence that comes along with the modulation of TGF-beta 1 activity and the reversion of the myofibroblastic phenotype by PRGF.This study was fully supported by BTI Biotechnology Institute, a dental implant company that investigates in the fields of oral implantology and PRGF-Endoret technology. MF and FM received a salary as scientists from BTI Biotechnology Institute. EA is the Scientific Director and president of BTI Biotechnology Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Plasma Rich in Growth Factors Membrane as Coadjuvant Treatment in the Surgery of Ocular Surface Disorders

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.14.2 (4.8-22.8) months, the mean ICT was 2.5 +/- 1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 +/- 2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 +/- 1.2 (1-4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P.05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis.This study received funding from the Ministry of Economy and Competitiveness of the Spanish Government, within the project denominated SURFEYE (reference RTC-2014-2375-1)

La oftalmología en la obra del escritor mexicano Octavio Paz (I)

1905-2016年までの112年間に出版された文献に基づき，日本産淡水魚類から記録された線虫類の情報を寄生虫－宿主リストと宿主－寄生虫リストに整理した。これまでに2綱3目17科に属する線虫類が報告され，52名義種が記録された。そのうち，以下の10科に含まれる30名義種と未同定種の情報を本前篇で示す。各科に属する名義種数は次の通りである：ドリライムス綱ディオクトフィメ目の腎虫科（1種）；同綱鞭虫目の毛細線虫科（4種）；クロマドラ綱旋尾線虫目の頭飾線虫科（0種），鰾線虫科（2種），海回虫科（4種），兜線虫科（2種），大口線虫科（3種），魚線虫科（7種），極細線虫科（1種），顎口虫科（6種）。本目録には種まで同定されなかった線虫類の情報も含む。Information on the nematodes of freshwater fishes of Japan published during 112 years between 1905 and 2016 is assembled as Parasite-Host and Host-Parasite lists. Fiffty-two nominal species and some unidentified species of the nematodes in 17 families, 3 orders, and 2 classes were reported during this period. The first part of this checklist includes 30 nominal species in the following nine families: Dioctophymatidae (1 species) in the order Dictophymatida, and Capillariidae (4 species) in the order Trichocephalida (class Dorylaimea); Anguillicolidae (2 species), Anisakidae (4 species), Camallanidae (2 species), Cucullanidae (3 species), Cystidicolidae (7 species), Daniconematidae (1 species), and Gnathostomatidae (6 species) in the order Spriruida (class Chromadorea). Information is also given on the nematodes of Acuariidae and other families that were not identified to species level

Eye bank versus surgeon prepared DMEK tissues: influence on adhesion and re-bubbling rate

AIM: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues. METHODS: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study. RESULTS: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02). CONCLUSIONS: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates

Consensus document on allergic conjunctivitis (DECA)

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms