Quantitative MR imaging study of intravitreal sustained release of VEGF in rabbits.
نویسندگان
چکیده
PURPOSE To determine whether sustained elevation of vascular endothelial growth factor (VEGF) in the vitreous cavity causes retinal hyperpermeability [blood-retinal barrier (BRB) breakdown] before the development of retinal neovascularization (NV) and to document the kinetics of the integrity of BRB breakdown versus time. METHODS Poly(L-lactide-co-glycolide)based devices loaded with VEGF were implanted intravitreally in rabbit eyes. Contrast-enhanced magnetic resonance imaging (MRI) methods were used to identify and quantitate the retinal permeability at various time points after implantation. This was done with the newly developed MR tracer AngioMARK (Epix Medical, Boston, MA). After the MRI measurements, fundus photography and fluorescein angiography (FA) also were performed on the same set of animals. RESULTS At 3 days after implantation, the MR images showed a significant retinal leakage into the vitreous cavity (BRB breakdown) of the VEGF-implanted eyes. To quantitate this leakage, the permeability surface area product (PS) was measured. At 3 days, the mean PS product was 1.25 +/-0.25 x 10(-5) cm3/min. Based on the VEGF in vitro release study, this 3-day BRB breakdown corresponded to a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. The fundus and FA photographs of these VEGF-implanted eyes taken at 4 days after implantation also showed a considerable level of retinal vascular dilation and tortuosity. By 12 days after implantation, the mean PS product decreased to 5.83 +/- 1.38 x 10(-6) cm3/min. However, the retinal NV was observed only after the second week after implantation. By this time, a total of 10.70 +/- 0.92 microg/ml of VEGF was released in a sustained fashion. Also, after the retinal NV development, retinal detachment also was observed. The control eyes, however, which were implanted with blank devices, remained unchanged and normal during the entire course of this study (PS = 5.57 +/- 0.66 x 10(-7) cm3/min). CONCLUSIONS. The findings indicate that sustained delivery of elevated amounts of VEGF in the vitreous cavity induces a BRB breakdown even earlier than 3 days after implantation. This was achieved after a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. This retinal leakage regressed by more than half by the time the retinal NV developed. Furthermore, a retinal detachment occurred after this retinal NV. These results are similar to proliferative diabetic retinopathy (PDR). The sustained elevation of VEGF in the vitreous cavity of rabbit eyes is potentially a good model to test VEGF antagonists to treat or prevent PDR in humans. The quantifiable change of BRB breakdown by the contrast-enhanced MRI method is ideal to assess the therapeutic intervention in vivo without killing the animal and may prove to be clinically useful in humans.
منابع مشابه
Evaluation of the Vascular Density, the Area of Foveal Avascular Zone, and Corrected Vision in Patients with Diabetic Macular Edema after Anti-VEGF Therapy
Background and Objective: This study aimed to evaluate the changes in macular superficial and deep capillary plexus (SCP and DCP) density, Foveal Avascular Zone (FAZ) area, and visual acuity in patients with diabetic macular edema after anti-VEGF therapy. Materials and Methods: This descriptive-analytical study utilized before and after treatment design. In total, 30 eyes of 30 patients with d...
متن کاملEvaluation of intravitreal injection of pentoxifylline in experimental endotoxin-induced uveitis in rabbits
The objective of the present study was to investigate the clinical and histopathological effects of intravitreal injection of pentoxifylline (PTX) the management of an experimental model of uveitis. Fifty-two rabbits were divided randomly into six intravitreal treated groups as below: 1) Balanced salt solution (BSS), 2) Salmonella typhimurium lipopolysaccharide endotoxin (LPS) + BSS, 3...
متن کاملSustained Release of Risedronate from PLGA Microparticles Embedded in Alginate Hydrogel for Treatment of Bony Lesions
Background: Inflammatory bone resorption in periodontitis can lead to tooth loss. Systemic administration of bisphosphonates such as risedronate for preventing bone resorption can cause adverse effects. Alginate hydrogel (ALG) and poly (lactic acid-co-glycolic acid) (PLGA) microparticles have been studied as drug delivery systems for sustained release of drugs. Therefore, the release pattern of...
متن کاملPharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits
The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid-co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performe...
متن کاملCoaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies
Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to en...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Investigative ophthalmology & visual science
دوره 41 6 شماره
صفحات -
تاریخ انتشار 2000