Matrix Metalloproteinases ; Neovascularization, Pathologic ; Neovascularization, Physiologic

Vascular endothelial growth factor (VEGF) is a protein secreted by cells to stimulate angiogenesis, a complex biological phenomenon essential for the development of new blood vessels. Aberrant angiogenesis has been implicated in various retinal diseases such as age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. Ever since the concept of angiogenesis was first introduced by Judah Folkman, and its crucial role in the pathophysiology of retinal diseases was elucidated by many scientists, much effort focused on identifying treatments has led to the development of anti-VEGF agents, which have become a critical component in the treatment of various retinal diseases associated with pathological angiogenesis. The application of various anti-VEGF agents has achieved not only the resolution of pathological lesions associated with aberrant angiogenesis, but also an improvement of visual acuity unattainable with conventional treatment modalities. Despite these major accomplishments with the use of anti-VEGF agents, there are still issues remaining to be addressed, such as how to treat non-responders to anti-VEGF agents, the need for repeated injections, and the economic burden on patients. This review highlights the outcomes from major clinical trials investigating the efficacy and safety of various anti-VEGF agents that are currently available and how they can be utilized in the daily clinical setting.
Bevacizumab ; Biological Phenomena ; Blood Vessels ; Diabetic Retinopathy ; Endothelial Growth Factors* ; Humans ; Macular Degeneration ; Neovascularization, Pathologic ; Ranibizumab ; Retinal Diseases* ; Retinal Vein Occlusion ; Vascular Endothelial Growth Factor A ; Visual Acuity

Photodynamic therapy (PDT) involves the induction of endothelial cell death or occlusion of blood vessels. On the basis of this mechanism of action, PDT is used in the treatment of predominant classic choroidal neovascularization (CNV), if the classic component is over 50%, and in myopic CNV. This study describes 2 cases of distinctive, abnormal, large, subretinal new vessels that are thought to have originated from the choroids. Diminishment of the new vessels was observed following treatment with PDT.
Retinal Vessels/drug effects/*pathology ; Retinal Diseases/*drug therapy/pathology ; *Photochemotherapy ; Neovascularization, Pathologic/*drug therapy/pathology ; Middle Aged ; Male ; Humans ; Female ; Angiography

PURPOSE: To evaluate the relationship between pericytes and endothelial cells in retinal neovascularization through histological and immunofluorescent studies. METHODS: C57BL/6J mice were exposed to hyperoxia from postnatal day (P) 7 to P12 and were returned to room air at P12 to induce a model of oxygen-induced retinopathy (OIR). The cross sections of enucleated eyes were processed with hematoxylin and eosin. Immunofluorescent staining of pericytes, endothelial cells, and N-cadherin was performed. Microfluidic devices were fabricated out of polydimethylsiloxane using soft lithography and replica molding. Human retinal microvascular endothelial cells, human brain microvascular endothelial cells, human umbilical vein endothelial cells and human placenta pericyte were mixed and co-cultured. RESULTS: Unlike the three-layered vascular plexus found in retinal angiogenesis of a normal mouse, angiogenesis in the OIR model is identified by the neovascular tuft extending into the vitreous. Neovascular tufts and the three-layered vascular plexus were both covered with pericytes in the OIR model. In this pathologic vascularization, N-cadherin, known to be crucial intercellular adhesion molecule, was also present. Further evaluation using the microfluidic in vitro model, successfully developed a microvascular network of endothelial cells covered with pericytes, mimicking normal retinal angiogenesis within 6 days. CONCLUSIONS: Pericytes covering endothelial cells were observed not only in vasculature of normal retina but also pathologic neovascularization of OIR mouse at P17. Factors involved in the endothelial cell-pericyte interaction can be evaluated as an attractive novel treatment target. These future studies can be performed using microfluidic systems, which can shorten the study time and provide three-dimensional structural evaluation.
Animals ; Brain ; Cadherins ; Endothelial Cells ; Eosine Yellowish-(YS) ; Fungi ; Hematoxylin ; Human Umbilical Vein Endothelial Cells ; Humans ; Hyperoxia ; In Vitro Techniques ; Lab-On-A-Chip Devices ; Mice ; Microfluidics ; Microvessels ; Neovascularization, Pathologic ; Pericytes ; Placenta ; Retina ; Retinal Neovascularization ; Retinaldehyde

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.
Humans ; Organoids ; Neovascularization, Pathologic ; Technology

PURPOSE: To report the occurrence of central vein occlusion in an Eales disease patient. CASE SUMMARY: A 23-year-old man presented with decreased left eye visual acuity and was diagnosed with bilateral Eales disease after ophthalmic evaluations. The patient received laser photocoagulation and visual acuity in his left eye improved 1 month after treatment. He was followed up regularly for 3 years and had no specific eye problems. Subsequently, the patient visited our clinic because of visual disturbance in his right eye. The patient's visual acuity was 0.6 in his right eye, and 1.0 in his left eye. On right eye fundus examination, there were multiple flame shape hemorrhages and retinal vascular tortuosity was observed. Arteriovenous transit time was extended on fluorescein angiography. Therefore, the patient was diagnosed with central retinal vein occlusion and underwent an internal medical examination to reveal a possible systemic cause of the central retinal vein occlusion; however, there were no systemic problems. Macular edema was observed on optical coherence tomography and the patient received an intravitreal bevacizumab injection. Six months after treatment, the right eye visual acuity and macular edema improved. CONCLUSIONS: Reports of branched retinal vein occlusion on the peripheral retina are common in Eales disease patients. However, the authors experienced and report a case of central retinal vein occlusion occurring in Eales disease.
Antibodies, Monoclonal, Humanized ; Eye ; Fluorescein Angiography ; Hemorrhage ; Humans ; Light Coagulation ; Macular Edema ; Neovascularization, Pathologic ; Retina ; Retinal Vasculitis ; Retinal Vein ; Retinal Vein Occlusion ; Retinaldehyde ; Tomography, Optical Coherence ; Veins ; Visual Acuity ; Young Adult ; Bevacizumab

Humans ; Microvessels ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Plaque, Atherosclerotic ; pathology

Thrombospondin-1 (TSP-1) is widely distributed in human tissues and is important in inhibiting angiogenesis.It also occupies an indispensable position in the formation, growth, differentiation, and metastasis of tumors in different tissues.TSP-1 plays an important role in the occurrence and development of various types of tumors. The inhibitory effect of TSP-1 on the angiogenesis and tumor development of oral and maxillofacial malignant tumors has been demonstrated in recent years. This paper reviews the findings and progress of TSP-1 research involving all kinds of tumors as well as oral and maxillofacial malignancies.
Humans ; Neoplasms ; Neovascularization, Pathologic ; Thrombospondin 1

Choroidal neovascular membranes are often poorly defined on fluorescein angiography because of fluorescein leakage or blockage of hyperfluorescence by overlying hemorrhage, lipid, turbid fluid, or pigment. Indocyanine green (ICG) is a highly protein-bound dye in the near infrared portion of the spectrum. Therefore, ICG remained in and around the neovascular membrane and enhanced the visualization of certain membranes poorly defined with fluorescein. ICG penetrated through the overlying turbid tissue, and improved the visualization of the underlying choroidal neovascular membrane. Using an infrared angiography system, the authors obtained 21 ICG-angiograms with suspected choroidal neovascularization, and compared them to fluorescein angiograms. In 5 of the 21 eyes, occult choroidal neovascularization was well delineated on the ICG angiograms. In 2 eyes, we were able to detect a well-defined choroidal neovascular membrane underlying a subretinal hemorrhage. In 12 of the 21 eyes with choroidal neovascular membrane, we performed argon-green laser photocoagulation applying the overlay technique of the ICG angiogram to red-free photo or the early fluorescein angiogram, and evaluated the effect of full coverage laser treatment.
Choroid/*blood supply ; Female ; Fluorescein Angiography/*methods ; Fundus Oculi ; Humans ; Indocyanine Green/*diagnostic use ; *Laser Coagulation ; Macular Degeneration/*complications ; Male ; Middle Aged ; Neovascularization, Pathologic/diagnosis/etiology/*surgery ; Retinal Hemorrhage/complications ; Signal Processing, Computer-Assisted ; Visual Acuity

BACKGROUNDNeovascularization can cause vision loss in proliferative diabetic retinopathy (PDR) and may be affected by many factors. Stromal cell-derived factor-1 (SDF-1) is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor (VEGF) in the eyes with diabetic retinopathy.

METHODSThe levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole (IMH). Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry.

RESULTSThe vitreous concentration of VEGF was significantly higher in eyes with PDR ((2143.7 +/- 1685.21) pg/ml) than in eyes with IMH ((142.42 +/- 72.83) pg/ml, P < 0.001). The vitreous level of SDF-1 was also significantly higher in eyes with PDR ((306.37 +/- 134.25) pg/ml) than in eyes with IMH ((86.91 +/- 55.05) pg/ml, P < 0.001). The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation (PRP) could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR (r = 0.61, P < 0.001). The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes.

CONCLUSIONSSDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.

Chemokine CXCL12 ; metabolism ; Diabetic Retinopathy ; metabolism ; pathology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Neovascularization, Pathologic ; metabolism ; physiopathology ; Retinal Perforations ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vitrectomy ; Vitreous Body ; metabolism