The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats

The aims of this study were to evaluate the effects of CM082 on the development of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to determine the drug concentration in the ocular tissues. After the laser-induced CNV model was established in rats, CM082 was orally administered. The effects of CM082 on the CNV lesions were assessed using fundus fluorescein angiography (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly less neovascularization than did the control group. The total concentration of CM082 in the eyes (172.86 ± 57.11 ng/g) was similar to that in the plasma (196.87 ± 73.13 ng/ml). Within the eye, the concentrations of CM082 and its metabolites were highest in the retina-sclera. The orally administered CM082 thus effectively passed through the blood-retina barrier (BRB) to reach the retina in the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was able to reduce CNV lesions in the laser-induced CNV rat model.

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Mechanism of Hypoxia Inducible Factor-1α (HIF-1α) in Choroidal Neovascularization in Macular Lutea of High Myopia

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2876 ◽

2022 ◽

Vol 12 (1) ◽

pp. 105-111

Author(s):

Lishuai Xu ◽

Qian Shi ◽

Dan Liao ◽

Zhen Yang ◽

Xiaoli Yang ◽

...

Keyword(s):

Choroidal Neovascularization ◽

Pigment Epithelium ◽

Quantitative Polymerase Chain Reaction ◽

Retinal Pigment ◽

Hypoxia Inducible Factor ◽

Group Versus ◽

Test Group ◽

Expression Level ◽

Control Group ◽

And Control

To explore the changes in the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the process of choroidal neovascularization (CNV) in the macular area of cases with form deprivation myopia (FDM), in this study, 36 healthy mice were selected as research subjects for analysis. Specifically, they were randomly divided into test group (n = 18) and control group (n = 18). The right eye of the test group mice underwent form deprivation for 6 weeks to induce FDM, also known as FDM group. Five mice were randomly selected from FDM group and control group at 6 time points (before photocoagulation, at 7 d, 14 d, 21 d, 28 d, and 35 d after photocoagulation), respectively, for fluorescein angiography and hematoxylin-eosin staining (HE) staining to observe differences in the retina. It was found that the retina of Control group mice was well-structured with clear stratification, while that of the test group mice was severely damaged with a disordered structure, manifested as edema and swelling and damaged Bruch membrane and retinal pigment epithelium (RPE) layer. Furthermore, macrophages and RPE cells were observed in the photocoagulation area, and there was a high-fluorescence area with a blurred margin in the fundus, indicating the formation of new blood vessels. The immunohistochemical experiment revealed that within three weeks after the surgery, HIF-1α was highly expressed in the test group, and the expression level was obviously higher than the Control group. The real-time quantitative polymerase chain reaction (PCR) results showed that the expression level of VEGF and HIF-α in the test group was obviously higher than the Control group within three weeks after the surgery. The Western blot experiment was performed 1 week after the surgery, and it was noted that the expression level of VEGF and HIF-1α were higher in the test group versus the Control group. In summary, HIF-1α is instrumental in ocular CNV, which is also associated with VEGF.

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Anti-VEGFR2 Antibody-modified Micelle for Triggered Drug Delivery and Effective Therapy of Choroidal Neovascularization

Current Neurovascular Research ◽

10.2174/1567202616666190619150956 ◽

2019 ◽

Vol 16 (3) ◽

pp. 258-265

Author(s):

Kei Takahashi ◽

Tomomi Masuda ◽

Mitsunori Harada ◽

Tadashi Inoue ◽

Shinsuke Nakamura ◽

...

Keyword(s):

Drug Delivery ◽

Choroidal Neovascularization ◽

Pigment Epithelium ◽

Drug Carrier ◽

Retinal Pigment ◽

Laser Coagulation ◽

Antiangiogenic Agents ◽

Drug Carrier System ◽

Novel Drug ◽

Drug Delivery Devices

Objective: This study aimed to examine whether DC101 (anti-VEGFR2 antibody)- modified micelles have applications as novel drug delivery devices, which allow small molecule antiangiogenic agents to deliver to angiogenic sites on a murine laser-induced choroidal neovascularization (CNV) model. Materials and Method: CNV was induced by photocoagulation on the unilateral eye of each mouse under anesthesia. Immediately after laser coagulation, E7974-loaded DC101-modified micelles and motesanib-loaded DC101-modified micelles were intravitreally administrated. Two weeks after photocoagulation, CNV was visualized using fluorescein-conjugated dextran (MW=2,000 kDa), and the CNV area was measured in retinal pigment epithelium (RPE)-choroidal flat mounts. Results: Intravitreal administration of both DC101-modified micelles loaded with E7974 at 2 µM and motesanib at 2 µM significantly reduced CNV area in the murine laser-induced CNV model at a clearly lower concentration than the effective dose of each agent. Conclusion: These results suggest that DC101-modified micelle might be effective drug carrier system for treating CNV and other ocular angiogenic diseases.

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Lactucaxanthin protects retinal pigment epithelium from hyperglycemia-regulated hypoxia/ER stress/VEGF pathway mediated angiogenesis in ARPE-19 cell and rat model

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.174014 ◽

2021 ◽

Vol 899 ◽

pp. 174014

Author(s):

Rani Elavarasan Anitha ◽

Rajasekar Janani ◽

Divya Peethambaran ◽

Vallikannan Baskaran

Keyword(s):

Retinal Pigment Epithelium ◽

Er Stress ◽

Rat Model ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Vegf Pathway

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Choroidal neovascularization associated with combined hamartoma of retina and retinal pigment epithelium: Multimodal imaging

Indian Journal of Ophthalmology ◽

10.4103/ijo.ijo_992_18 ◽

2018 ◽

Vol 66 (12) ◽

pp. 1866 ◽

Cited By ~ 2

Author(s):

Jay Chhablani ◽

Rajan Gupta ◽

RajeevR Pappuru ◽

VivekP Dave

Keyword(s):

Retinal Pigment Epithelium ◽

Choroidal Neovascularization ◽

Multimodal Imaging ◽

Pigment Epithelium ◽

Retinal Pigment

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Focal Choroidal Excavation in a Case of Choroidal Osteoma Associated with Choroidal Neovascularization

Journal of Ophthalmic and Vision Research ◽

10.18502/jovr.v15i3.7461 ◽

2020 ◽

Author(s):

Mahdieh Azimizadeh ◽

Seyedeh Maryam Hosseini ◽

Esmaeil Babaei

Keyword(s):

Choroidal Neovascularization ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Subretinal Fluid ◽

Retinal Hemorrhage ◽

Retinal Layers ◽

Choroidal Osteoma ◽

Focal Choroidal Excavation ◽

Neurosensory Retina ◽

The Right

Purpose: To report a case of choroidal osteoma associated with reactivation of choroidal neovascularization (CNV) and development of focal choroidal excavation (FCE). Case Report: A 34-year-old woman with choroidal osteoma complicated by CNV in the right eye for two years presented with deterioration of visual acuity in her right eye. A small retinal hemorrhage accompanied by subretinal fluid (SRF) was seen in the macular area of the right eye. Optical coherence tomography (OCT) showed that the inner retina was intact, and the outer retinal layers had outward displacement. SRF and a wedge-shaped choroidal depression were also seen. This choroidal excavation was not present on previous OCT images. The integrity of the inner retinal layers was maintained, and an optically clear space was present between the neurosensory retina and the retinal pigment epithelium. Conclusion: Choroidal osteoma can be complicated by CNV and FCE could occur as a consequence. Again, FCE can lead to CNV development. This cascade can deteriorate vision and sometime lead to permanent visual loss.

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Association of Thiol–disulfide Homeostasis with Retinal Layer Thickness in Patients with Diabetes Mellitus

10.21203/rs.3.rs-791653/v1 ◽

2021 ◽

Author(s):

Muhammet Cuneyt Bilginer ◽

Abbas Ali Tam ◽

Berna Evranos Ogmen ◽

Bagdagul Yuksel Guler ◽

Nagihan Ugurlu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Layer Thickness ◽

Disease Duration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Control Group ◽

Retinal Layer ◽

Healthy Controls ◽

Total Thiol

Abstract Background: This study aimed to investigate the relationship between early changes in retinal layer thickness and thiol–disulfide homeostasis in patients with type II diabetes mellitus (T2DM).Materials-Methods: There were 69 patients with T2DM (61 patients without retinopathy, 8 patients with retinopathy) and 21 healthy controls. In patients without retinopathy, 31 of the patients had a disease duration under 10 years, 30 of the patients had a disease duration over 10 years. Retinal layer thickness of the right eye was measured using Spectral Domain Optical Coherence Tomography. Results: Patients with T2DM and healthy controls had mean ages of 48.40 ± 8.25 years and 45.94 ± 7.32 years, respectively. The ganglion cell layer and retinal pigment epithelium thicknesses were significantly lesser in patients without diabetic retinopathy than those in the control group. In patients without diabetic retinopathy and with a disease duration of under 10 years, there was a negative correlation between the retinal nerve fiber layer thickness (µm) and disulphide/total thiol ratio, between the inner nuclear layer thickness (µm) and disulphide/native thiol ratio as well as disulphide/total thiol ratio (r= −0.376, p= 0.037; r= −0.356, p= 0.050; r= −0.380, p= 0.035, respectively) and positive correlation between the INL thickness (µm) and native thiol/total thiol ratio (r= 0.359, p= 0.047).Conclusion: Early changes in retinal layers in patients with DM were associated with thiol–disulfide homeostasis. Administration of therapeutic supplements may aid in the management of low thiol concentrations; this increases the importance of the study findings.

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The Effects of Indocyanine Green Dye-Enhanced Photocoagulation on the Blood Flow in the Choriocapillaris and the Choroidal Neovascularization (CNV)

10.1115/imece2000-2213 ◽

2000 ◽

Author(s):

C. von Kerczek ◽

L. Zhu ◽

A. Ernest ◽

C. Eggleton ◽

L. D. T. Topoleski ◽

...

Keyword(s):

Laser Treatment ◽

Choroidal Neovascularization ◽

Vision Loss ◽

Pigment Epithelium ◽

Retinal Pigment ◽

The United States ◽

Age Related Macular Degeneration ◽

Central Vision ◽

Age Related ◽

Direct Laser

Abstract Age-related macular degeneration (AMD) is the most common cause of vision loss in patients aged 65 years and older in the United States. In the majority of cases, the loss of central vision is secondary to exudative changes and fibrovascular scarring following choroidal neovascularization (CNV). Prompt laser treatment is recommended [Asrani et al., 1996; Macular Photocoagulation Study Group, 1993; Schneider et al, 1998]. However, direct laser treatment to the entire subfoveal lesion is almost invariably associated with immediate loss of central vision. Loss of central vision may be due to direct damage to foveal photoreceptors and retinal pigment epithelium or from damage to the nerve fiber layer serving foveal function [Han et al., 1988].

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