fibrin and Retinal-Diseases

In December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract. However, further studies documented other systemic involvement. This study investigates histopathologic eye changes in postmortem material of coronavirus disease 2019 (COVID-19) patients.. Sections of formalin-fixed, paraffin-embedded eyes from 5 patients (10 eyes) who died of COVID-19 at the University Hospital in Basel were included. Gross examination and histological evaluation were performed by 3 independent ophthalmopathologists. Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3, and ACE-2. Five enucleated eyes of patients not infected with SARS-CoV-2 served as control group. All cases have been studied for presence of SARS-CoV-2 RNA by means of reverse transcription PCR and RNA in situ hybridization (ISH). The choroidal vessels of one case were analyzed with electron microscope.. Ophthalmopathologically, 8 eyes from 4 patients displayed swollen endothelial cells in congested choroidal vessels. No further evidence of specific eye involvement of SARS-CoV-2 was found in any of the patients. In the 8 eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina, and choroidea and displayed significantly lower amounts of stained cells as in COVID-19 eyes. SARS-CoV-2 RNA was detectable in both bulbi of 2/5 patients, yet ISH failed to visualize viruses. Electron microscopy showed no significant results due to the artifacts.. As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, that is, hypercoagulation and vasculopathy most probably due to endothelial damage. A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. The expression of ACE-2 receptors in the conjunctiva hints toward its susceptibility to infection. To what extend eyes, function is disrupted by SARS-CoV-2 is subject to further studies, especially in the clinic.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme 2; Caspase 3; Choroid; Choroid Diseases; Ciliary Body; Conjunctiva; Cornea; COVID-19; COVID-19 Nucleic Acid Testing; Endothelial Cells; Eye Infections, Viral; Female; Fibrin; Humans; Immunohistochemistry; In Situ Hybridization; Male; Real-Time Polymerase Chain Reaction; Retinal Diseases; Retinal Vessels; RNA, Viral; SARS-CoV-2; Thrombosis

Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision.. Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders.. In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells.. Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration.

Topics: Animals; Cell Differentiation; Conjunctiva; Fibrin; Gels; Humans; Hydrogels; Mesenchymal Stem Cells; Photoreceptor Cells, Vertebrate; Retina; Retinal Diseases; Tissue Engineering; Tissue Scaffolds

Oxygen-induced retinopathy (OIR) is a well-characterized model for retinopathy of prematurity, a disorder that results from rapid microvascular proliferation after exposure of the retina to high oxygen levels. Here, we report that the proliferative phase of OIR requires transcriptional induction of the annexin A2 (A2) gene through the direct action of the hypoxia-inducible factor-1 complex. We show, in addition, that A2 stabilizes its binding partner, p11, and promotes OIR-related angiogenesis by enabling clearance of perivascular fibrin. Adenoviral-mediated restoration of A2 expression restores neovascularization in the oxygen-primed Anxa2(-/-) retina and reinstates plasmin generation and directed migration in cultured Anxa2(-/-) endothelial cells. Systemic depletion of fibrin repairs the neovascular response to high oxygen treatment in the Anxa2(-/-) retina, whereas inhibition of plasminogen activation dampens angiogenesis under the same conditions. These findings show that the A2 system enables retinal neoangiogenesis in OIR by enhancing perivascular activation of plasmin and remodeling of fibrin. These data suggest new potential approaches to retinal angiogenic disorders on the basis of modulation of perivascular fibrinolysis.

Topics: Animals; Annexin A2; Aorta; Blotting, Western; Cell Movement; Cells, Cultured; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrinolysin; Fibrinolysis; Flow Cytometry; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Immunoprecipitation; Luciferases; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic; Oxygen; Plasminogen Activators; Promoter Regions, Genetic; Retinal Diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA Stability; RNA, Messenger; Transfection; Umbilical Veins

To study the optical coherence tomography (OCT) pattern of the fluorescein angiographic leakage in acute central serous chorioretinopathy (CSCR).. This is a non-interventional pilot case study. OCT line scan was performed over the fluorescein angiographic leak site in eyes clinically diagnosed acute CSCR. Clinical fundus photograph, site of leakage on fundus fluorescein angiography and corresponding OCT were analysed.. The mean age of 10 consecutive patients was 38.8 +/- 6.9 years. Six patients were male and the mean duration of symptom was 7 days. Six eyes (60%) showed a characteristic dipping pattern of neurosensory retina with intervening hyper-reflective echoes suggestive of fibrin over the leakage site. All these eyes had ink-blot leak and subretinal fibrin.. Ink-blot leak in acute CSCR with subretinal fibrin generates a dipping morphological pattern on OCT.

Topics: Acute Disease; Adult; Capillary Permeability; Choroid Diseases; Exudates and Transudates; Female; Fibrin; Fluorescein Angiography; Humans; Male; Middle Aged; Pilot Projects; Retinal Diseases; Retinal Vessels; Tomography, Optical Coherence

To report unusual and heretofore unreported visually damaging manifestations of severe central serous chorioretinopathy.. Case studies.. Each of six male patients (average age, 40 years) had a form of severe central serous chorioretinopathy with at least one eye containing fibrin in the subretinal space that then developed into a subretinal fibrotic scar. Scar formation was followed by a tenting up of the macula, vascularization of the fibrosis (subretinal neovascularization), or a retinal pigment epithelial rip. Four of the seven eyes with subretinal fibrosis had severe visual loss (20/400 or worse).. Subretinal fibrin and other extracellular matrix molecules appear to stimulate the retinal pigment epithelium to undergo fibrous metaplasia, which results in subretinal fibrotic scar formation and other sequelae, all of which can lead to severe visual loss.

Topics: Adult; Body Fluids; Choroid Diseases; Exudates and Transudates; Fibrin; Fibrosis; Fluorescein Angiography; Fundus Oculi; Humans; Male; Middle Aged; Retina; Retinal Detachment; Retinal Diseases; Vision Disorders; Visual Acuity

Laboratory and clinical observations have implicated microparticles in the pathogenesis of Purtscher's retinopathy, which leads to the occlusion of small arterioles. These microparticles may be caused by aggregated leukocyte platelets or fibrin clots. The phenomenon of intravascular coagulation is well known following trauma or acute pancreatitis. Purtscher's retinopathy is linked with both diseases. To support this presumed pathogenesis of Purtscher's retinopathy, fibrin clots ranging in size from 0.15 to 1.0 mm were injected into the ophthalmic artery of the pig. They resulted in superficial and deep retinal infarctions. In addition, flame-shaped and spotted hemorrhages occurred. These retinal changes are characteristic of Purtscher's retinopathy.

Topics: Animals; Blood Coagulation; Disease Models, Animal; Female; Fibrin; Fundus Oculi; Ophthalmic Artery; Retinal Artery Occlusion; Retinal Diseases; Retinal Hemorrhage; Swine

The authors injected 25 micrograms of recombinant tissue plasminogen activator (tPA) into the anterior chamber or vitreous cavity of 23 eyes of 22 patients with severe intraocular fibrin formation that developed after vitrectomy surgery for complicated cases of proliferative vitreoretinopathy (PVR) (13 eyes), diabetic traction retinal detachment (TRD) (7 eyes), or endophthalmitis (3 eyes). Tissue plasminogen activator injected an average (+/- standard deviation) of 73 +/- 63 hours after vitrectomy surgery resulted in complete fibrinolysis in 21 of 23 eyes and partial fibrinolysis in one eye. The mean time to fibrin resolution was 3.0 +/- 1.0 hours. Four eyes required repeat tPA injection for recurrent fibrin formation; repeat injection resulted in complete fibrinolysis in each case. The mean follow-up duration after tPA administration was 6 months. At the final follow-up examination, the retina was totally attached in 18 of 23 eyes and was partially attached in 2. Visual acuity improved in 12 eyes (52%); it was at least 20/400 in 8. Complications of tPA injection included hyphema (2 patients) and corneal stromal thickening (2 patients). Mild, transient, periocular pain that was easily managed with non-narcotic analgesia developed in three patients.

Topics: Adolescent; Adult; Aged; Anterior Chamber; Child; Endophthalmitis; Female; Fibrin; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Retinal Detachment; Retinal Diseases; Tissue Plasminogen Activator; Visual Acuity; Vitrectomy; Vitreous Body

Topics: Fibrin; Humans; Recombinant Proteins; Retinal Diseases; Tissue Plasminogen Activator; Vitrectomy

Local ocular hypothermia was evaluated in experimental open sky vitrectomy, closed vitrectomy, and anterior chamber irrigation and aspiration in 40 albino rabbits (80 eyes). The irrigating balanced salt solution was used at room temperature in control eyes and was cooled to 7 degrees C in experimental eyes. Experimental eyes demonstrated less intraocular bleeding volume, less fibrin production, and less postoperative inflammation. No detectable tissue intolerance to hypothermia was observed on short- or long-term follow-up.

Topics: Animals; Anterior Chamber; Eye Hemorrhage; Fibrin; Hypothermia, Induced; Inflammation; Postoperative Complications; Rabbits; Retinal Diseases; Retinal Hemorrhage; Vitrectomy

Eighty-five patients with retinal emboli, visible ophthalmoscopically, were studied retrospectively. All the patients had presented with transient or permanent visual loss. Follow up from the time of presentation was one year to 12 years with a mean of 4.5 years. Life expectancy in the 58 medically treated patients who presented with cholesterol emboli was significantly reduced (p = 0.028). Stroke was the commonest cause of death and was significantly more frequent than in the general population (p less than 0.001); there was also an increased total incidence of cerebrovascular disease (fatal and non-fatal) compared with the Oxfordshire Stroke Project (p less than 0.001). The mortality from ischaemic heart disease was not significantly increased. We report a series of 85 patients with retinal emboli, 69 of whom had cholesterol emboli (70 fundi), 15 calcific emboli and one platelet-fibrin embolus. The natural history of medically treated patients with cholesterol emboli is compared both with an age and sex matched population and with patients with amaurosis fugax but no visible retinal emboli.

Topics: Adult; Aged; Aged, 80 and over; Blindness; Calcinosis; Cholesterol; Embolism; Female; Fibrin; Humans; Male; Middle Aged; Platelet Aggregation; Prognosis; Retinal Artery; Retinal Diseases; Risk Factors

A male rhesus macaque was found to have what appeared to be numerous platelet-fibrin emboli in retinal vessels in the perimacular area. Indocyanine green (ICG) dye fluorescence and fluorescein angiograms of the fundus demonstrated leakage of fluorescein, but not ICG, from the involved arterioles. Histopathologic changes in the eyes included occlusion of retinal and choroidal vessels with platelet-fibrin emboli, inner retinal ischemia, ischemic injury to the parafoveal capillary bed distally to occlusion of precapillary arterioles, and retinal exudate limited to the regions of capillary damage. Differential leakage of fluorescein may be explained by the difference in binding affinities of the 2 dyes to blood protein: 20% to 40% of the circulating fluorescein is unbound, and 98% of ICG is bound to serum albumin. Simultaneously or serially performed angiograms with fluorescent probes of different sizes might be used to obtain a qualitative measure of vascular integrity in persons with embolism, diabetic retinopathy, sickle cell retinopathy, vasculitis, and other disorders known to produce focal retinal and choroidal vascular occlusion.

Topics: Animals; Blood Platelets; Embolism; Fibrin; Fluorescein; Fluorescein Angiography; Fluoresceins; Indocyanine Green; Male; Monkey Diseases; Retina; Retinal Diseases; Retinal Vessels

Retinal changes in accelerated hypertension were studied in seventeen monkeys with experimental hypertension by means of ophthalmoscopy and colour and flourescence photography during life, and by injection and digest preparations and light and electron microscopy after the animals had been killed. Cotton-wool spots developed in all but three monkeys. The arteries became tortuous and dilated and the light reflex decreased in those animals that became hypertensive. The earliest abnormality was a development of many points of fluorescein leakage on terminal arterioles or small arteries. Such leaking points were always present in relation to cotton-wool spots but were not confined to such areas. Focal narrowing of arteries was not observed but arteriolar occlusion and retrograde filling of the distal segment was present in three animals. Superficial linear haemorrhages were noted in five animals. Light microscopy revealed cotton-wool spots which were identical to those observed in man with a collection of swollen axons containing densely staining pseudonuclei. Study of the arterioles by electron microscopy showed findings ranging from normality to extensive necrosis. Many precapillary arteries were constricted and some were virtually occluded. Degenerative changes were present in smooth muscle cells in the wall of many of the constricted arterioles. Many arteries also showed insudation into their wall of plasma which had seeped into the muscular coat displacing and sometimes entirely replacing the smooth muscle cells. Except for arterioles with advanced necrosis, there was no indication of how plasma insudation occurred. Two arterioles with extensive necrosis showed a break within the endothelial cell cytoplasm through which penetration of plasma proteins had probably occurred. The extravascular tissues showed collections of amorphous material, sone of it with the typical banded configuration of fibrin. The sequence of events proposed to explain these features is as follows: (1) The arterioles constrict as the pressure rises, most likely as a result of vascular autoregulation. This may head to occlusion of the precapillary arterioles and is associated with necrosis of vascular smooth muscle. (2) Dilatation then occurs with insudation of plasma into the unsupported wall through a damaged endothelium. This stage probably corresponds to the autoregulatory break-point and is evidenced clinically by focal leakage of fluorescein. (3) Progressive plasma insudation

Topics: Animals; Arterial Occlusive Diseases; Basement Membrane; Blood Flow Velocity; Blood Pressure; Capillaries; Dilatation; Fibrin; Fluorescein Angiography; Haplorhini; Hypertension, Malignant; Muscle, Smooth; Necrosis; Ophthalmoscopy; Reflex, Pupillary; Retina; Retinal Artery; Retinal Diseases; Urea

We wished to know if excision of artificially produced intravitreal vessels would cause bleeding and if the hemorrhage could be controlled by increasing the intraocular pressure. In 17 rabbit eyes, the distal end of several intravitreal blood vessels was excised and removed by the Peyman vitrophage. No significant bleeding occurred from the vessels in 13 eyes, and in the remaining four bleeding stopped after 30 seconds or less of increased intraocular pressure. In one month of observation after surgery, there was no evidence of delayed hemorrhage. Electron microscopy of several transected intravitreal vessels revealed that vessel constriction, platelets and fibrin strands contributed to the prevention of immediate and delayed hemorrhage.

Topics: Ammonium Chloride; Animals; Disease Models, Animal; Endothelium; Erythrocytes; Eye Diseases; Fibrin; Hemorrhage; Hemostasis; Intraocular Pressure; Microscopy, Electron; Postoperative Complications; Rabbits; Retinal Diseases; Retinal Vessels; Time Factors; Vitreous Body

Topics: Adult; Aged; Anemia, Hemolytic; Blood Cell Count; Creatinine; Erythrocytes; Female; Fibrin; Fibrinogen; Fluorescein Angiography; Humans; Hypertension; Iodine Isotopes; Kidney Diseases; Male; Middle Aged; Retinal Diseases; Retinal Vessels

Topics: Anemia, Sickle Cell; Animals; Anticoagulants; Coumarins; Fibrin; Heparin; Humans; Male; Priapism; Pulmonary Embolism; Retinal Diseases; Retinal Vessels; Snakes; Thrombosis; Venoms