Abstract:
PURPOSE:This study was aimed at determining the intraocular pharmacokinetics based on molecular physicochemical properties in a rabbit model. METHODS:The entire dataset was obtained from previous literature, and research articles regarding 70 molecular compounds were investigated. The intravitreal half-lives in rabbit eyeballs of 22 macromolecules and 48 micromolecules were analyzed. Multiple linear regression analysis was carried out with non-collinear independent variables (molecular weight [MW] and lipophilicity) influencing intravitreal half-lives. The best-fit equations were selected based on the correlation coefficients and goodness-of-fit statistics. RESULTS:The best-fit models obtained from the entire dataset, macromolecules, and micromolecules suggest the correlation between molecular physicochemical properties (MW and lipophilicity) and intravitreal half-life. Exclusion of outlier molecules (amphotericin B and foscarnet) leads to a better-fit correlation. MW is the definite single factor affecting intravitreal half-lives of macromolecules (Log t1/2 = 0.148 + 0.370 Log MW, R2 = 0.769), while both MW and lipophilicity influence the intraocular pharmacokinetics of micromolecules (Log t1/2 = -1.213 + 0.762 Log MW - 0.115 Log p, R2 = 0.554). CONCLUSION:The present study indicates that intravitreal half-life could be predicted based on molecular physicochemical properties (MW and lipophilicity). Also, increasing MW while reducing lipophilicity would be a reliable method for prolonging the intravitreal half-life of small chemical drugs, while MW is the single major determinant for large biologic drugs.
journal_name
Ophthalmic Resjournal_title
Ophthalmic researchauthors
Kim HM,Park KH,Chung JY,Woo SJdoi
10.1159/000499529subject
Has Abstractpub_date
2020-01-01 00:00:00pages
41-49issue
1eissn
0030-3747issn
1423-0259pii
000499529journal_volume
63pub_type
杂志文章abstract:OBJECTIVE:To evaluate the feasibility of a new technique for the implantation of ultrathin substrates containing stem cell-derived retinal pigment epithelium (RPE) cells into the subretinal space of retina-degenerate Royal College of Surgeon (RCS) rats. METHODS:A platform device was used for the implantation of 4-µm-t...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000338749
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVES:To evaluate the efficacy of postenucleation saline wash and the effect of different antimicrobial agents on the microbial contamination of donor eyes. METHODS:Two hundred donor eyes were given saline wash and treated with any one of the following 5 randomly selected antimicrobial solutions: 1% povidone-iodi...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000095772
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:To investigate the role of integrin-linked kinase (ILK) in endothelial cell migration, proliferation and tube formation in vitro. MATERIALS AND METHODS:Cultured RF/6A cells were knocked down for ILK using small interfering RNA (siRNA). Cellular ILK expression was quantified by real-time quantitative PCR and We...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000232971
更新日期:2009-01-01 00:00:00
abstract::In order to develop a more adequate ultraviolet (UV)-induced cataract model, a combination of l-buthionine sulfoximine (BSO) treatment was applied to experimental animals. A single administration of BSO 4 mmol/kg caused reduced glutathione concentration until experimental day 8. In the 0.067-J/cm2 UV-B irradiation exp...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267957
更新日期:1996-01-01 00:00:00
abstract::The aqueous humors of 100 freshly enucleated rabbit eyes were assessed within 10 min postmortem by taking samples in the last stage of corneal dissection following the Dikstein-Maurice procedure. Aqueous levels of partial pressure of carbon dioxide (pCO2) averaged 58.2 +/- 8.5 mm Hg to give calculated tCO2 and bicarbo...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267269
更新日期:1993-01-01 00:00:00
abstract::The turnover and migration of synthesized glycoproteins in the cultured retinal pigment epithelium have been studied. Quantitative study indicated that half-time of 3H-fucosylglycoproteins was 11.6 days. Autoradiography was performed several times after incubation of 3H-fucose. Retinal pigment epithelium constantly sy...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000265423
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To investigate the antiangiogenic effect of itraconazole for the prevention of experimentally induced corneal neovascularization and whether the efficacy depends on the route of administration. MATERIALS AND METHODS:Thirty-six rats were randomly divided into 6 groups with 6 rats in each group. Chemical cauteri...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000366283
更新日期:2014-01-01 00:00:00
abstract::To ascertain the effectiveness of topical antioxidant therapy on acute corneal inflammation, we have studied the effectiveness of topical treatment with a saline solution and with antioxidants such as 0.2% superoxide dismutase and 0.5% dimethylthiourea (DMTU) in a controlled experimental study. The evolution of the in...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267648
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To describe the characteristics of macular lesions after eye trauma using spectral-domain optical coherence tomography (OCT). METHODS:We retrospectively reviewed and described 2-dimensional (2D) and 3-dimensional (3D) spectral-domain OCT characteristics of 24 consecutive eyes of 24 cases that were identified w...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000325732
更新日期:2012-01-01 00:00:00
abstract::Two out of three normal eyes tested with frequent instillation of 30 microliters of drops of 0.5% bupranolol, a beta 1 + beta 2 blocking drug with some intrinsic sympathomimetic and local anesthetic activity, showed a miotic effect of the order of a 25% reduction of pupil area, as estimated by an open-loop iris-videor...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000265407
更新日期:1986-01-01 00:00:00
abstract::Soluble dextran polymer derivatives (CMDBSs) are originally synthesized as heparin-like plasma substitutes. Some of them mimic heparin in its interactions and stabilize, protect and facilitate actions of heparin binding growth factors. The wound healing activity of one specific CMDBS was studied in a model of corneal ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267497
更新日期:1994-01-01 00:00:00
abstract::We measured prostaglandin E2 (PGE2) and prostacyclin levels in the vitreous bodies of 5 eyes of patients with diabetic retinopathy complicated by rhegmatogenous retinal detachment (RRD) and compared them with the corresponding levels in 9 nondiabetic eyes with the same condition as well as with 10 control eyes of dece...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000266995
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:We assessed bleb morphology and the intraocular pressure (IOP)-lowering effect of trabeculectomy with ologen compared to mitomycin C (MMC) in juvenile open-angle glaucoma (JOAG). METHODS:This is a prospective interventional comparative study conducted on 40 eyes (20 patients) with medically uncontrolled JOA...
journal_title:Ophthalmic research
pub_type: 杂志文章,随机对照试验
doi:10.1159/000456719
更新日期:2017-01-01 00:00:00
abstract::Vitamin E (d-alpha-tocopherol) and aspirin were evaluated for their effects on the phase separation temperature, Tc, of calf lens cytoplasm. Vitamin E and aspirin were added to nuclear homogenate and the change in Tc was measured. Aspirin had no measurable effect on Tc. Vitamin E lowered Tc at a rate of -22 degrees C ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000265475
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. METHODS:Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic Retinopathy St...
journal_title:Ophthalmic research
pub_type: 杂志文章,多中心研究
doi:10.1159/000438793
更新日期:2015-01-01 00:00:00
abstract:AIM:To investigate the diagnostic efficacy and clinical application value of plasma endothelin-1 for diabetic retinopathy using receiver operating characteristic (ROC) curve analysis. METHODS:This was a prospective investigational study. Funduscopy and fundus fluorescein angiography were used as gold standards for the...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000108123
更新日期:2007-01-01 00:00:00
abstract::Cholinergic agents used to lower intraocular pressure in the medical management of glaucoma act on muscarinic receptors in the eye. Recently, subtypes of muscarinic receptors have been recognized in many tissues including the eye. To localize the M3 muscarinic receptor subtype and m3 messenger RNA (mRNA) in the human ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267472
更新日期:1994-01-01 00:00:00
abstract::The ultrastructure of optic nerve axons was examined in several mammals (human, cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and raised intra-ocular pressure (IOP). We describe accumulations of organelles (prin...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267739
更新日期:1995-01-01 00:00:00
abstract::The component oxygen fluxes that constitute a single recording of corneal oxygen uptake when a polarographic oxygen sensor (POS) is placed in contact with the cornea were determined in the in vivo rabbit eye by removing the epithelium and injecting an air bubble into the anterior chamber. The relative contribution of ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000265369
更新日期:1985-01-01 00:00:00
abstract::The aim of the study was to examine the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acid (ASA) on human lens epithelial cells (HLECs) during oxidative stress. HLECs were exposed to H2O2 in the absence or presence of indomethacin, diclofenac, celecoxib (NSAIDs) or ASA for 24 h. HLECs were a...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000113885
更新日期:2008-01-01 00:00:00
abstract::Autofluorescence and transmission values of the lens for blue-green light were determined at two locations with the use of identical fluorophotometers: in Coimbra, Portugal, in 44 healthy controls, 15 haemodialysis and 11 renal failure patients, and in Leiden, The Netherlands, in 57 healthy controls, 23 haemodialysis ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000266736
更新日期:1988-01-01 00:00:00
abstract::The high-voltage electron microscope (HVEM) permits examination of sections much thicker (up to 1 micron) than those usually used in transmission electron microscopy, which are approximately 70 nm in thickness. Two examples of the utility of the HVEM in research on the ultrastructure of the retinal pigment epithelium ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000265457
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Single-field non-mydriatic fundus photography (NMFP) has been used to detect diabetic retinopathy (DR) in many studies; however, its value in a general clinical setting has not been established. Here we performed a meta-analysis to evaluate its diagnostic effectiveness. METHOD:We systematically searched PubMed...
journal_title:Ophthalmic research
pub_type: meta分析
doi:10.1159/000499106
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:The aim of the present study was to characterize the development of after-cataract in the rabbit by measuring its wet weight, protein, DNA and glycosaminoglycan (GAG) contents and using Scheimpflug and slitlamp analysis. Further, aqueous humor (AqH) leukocytes, protein and lens epithelial cell proliferation act...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000048320
更新日期:2002-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the characteristics of corneal endothelial cells and central corneal thickness (CCT) in patients with diabetes mellitus (DM), comparing them with those of healthy subjects (controls) and to determine potential factors affecting the corneal parameters in patients with DM. M...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000507197
更新日期:2020-01-01 00:00:00
abstract::We hypothesize that the differential susceptibility to photic injury among different strains of rat retinas may depend on the levels of phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity, one of the endogenous antioxidant enzymes in the retina. The retinas of four inbred strains of albino rat (Fischer,...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267376
更新日期:1994-01-01 00:00:00
abstract::Cellular immune responses in retinal autoimmunity have scarcely been studied in rabbits. An effective isolation of rabbit peripheral blood lymphocytes is difficult to achieve and requires specific conditions. This hampers especially the assay of antigen-induced lymphocyte transformation. We have improved the lymphocyt...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000266934
更新日期:1989-01-01 00:00:00
abstract::Cannabinoid receptor involvement in the intraocular-pressure (IOP)-lowering effect of the cannabinoids has not been determined. These receptors bind four structural classes of agonists: the classical and the nonclassical cannabinoids, the aminoalkylindoles and the arachidonylethanolamides (the endogenous ligands). We ...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000267984
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND/AIM:Corneal epithelial defects may heal slowly in patients with diabetes, limbal stem cell deficiency, extensive chemical burns or anesthetized corneas. Studies have shown that erythropoietin, a glycoprotein hormone that promotes red blood cell proliferation and inhibits apoptosis of erythroid progenitors, m...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000351627
更新日期:2013-01-01 00:00:00
abstract:PURPOSE:To evaluate the corneal button of primary penetrating keratoplasty of patients diagnosed with congenital aniridia. The study took place at the Instituto Universitario Barraquer and the Centro de Oftalmología Barraquer. METHODS:A retrospective analysis of cases diagnosed with congenital aniridia was carried out...
journal_title:Ophthalmic research
pub_type: 杂志文章
doi:10.1159/000444930
更新日期:2016-01-01 00:00:00