Abstract：
:Prostaglandins are widely used to lower intraocular pressure (IOP) as part of the treatment regimen for glaucoma. While FP and EP2 agonists are known to lower IOP, we investigated the ocular hypotensive activity and ocular drug distribution of PF-04475270, a novel EP4 agonist following topical administration in normotensive Beagle dogs. PF-04475270 is a prodrug of CP-734432, which stimulated cAMP formation in HEK293 cells expressing EP4 receptor and beta-lactamase activity in human EP4 expressing CHO cells transfected with a cAMP response element (CRE) with an EC(50) of 1 nM. Prodrug conversion and transcorneal permeability were assessed in rabbit corneal homogenates and a human corneal epithelial cell (cHCE) model. The compound underwent rapid hydrolysis to CP-734432 in corneal homogenates, and exhibited good permeability in the cHCE model. The descending order of ocular exposure to CP-734432 after topical dosing of PF-04475270 in dogs was as follows: cornea > aqueous humor >or= iris/ciliary body. When administered q.d., PF-04475270 lowered IOP effectively in the dog IOP model both after single and multiple days of dosing. A maximum decrease in IOP with PF-04475270 was between 30 and 45% at 24h post-dose relative to that observed with vehicle. In conclusion, PF-04475270 is a novel ocular hypotensive compound which is bioavailable following topical dosing, effectively lowering IOP in dogs. EP4 agonists could be considered as potential targets for lowering IOP for the treatment of glaucoma and ocular hypertension.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Prasanna G,Fortner J,Xiang C,Zhang E,Carreiro S,Anderson S,Sartnurak S,Wu G,Gukasyan H,Niesman M,Nair S,Rui E,Lafontaine J,Almaden CD,Wells P,Krauss Adoi
10.1016/j.exer.2009.05.002subject
Has Abstractpub_date
2009-11-01 00:00:00pages
608-17issue
5eissn
0014-4835issn
1096-0007pii
S0014-4835(09)00134-1journal_volume
89pub_type
杂志文章abstract：:Myo/Nog cells are essential for eye development in the chick embryo and respond to injury in adult tissues. These cells express mRNA for the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein (BMP) inhibitor Noggin and the cell surface protein recognized by the G8 monoclonal antibody (m...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2015.11.023
更新日期：2016-05-01 00:00:00
abstract：:Binocular vision provides the most accurate and precise depth information; however, many people have impairments in binocular visual function. It is possible that other sensory inputs could be used to obtain reliable depth information when binocular vision is not available. However, it is currently unknown whether dep...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.08.013
更新日期：2019-06-01 00:00:00
abstract：:The rapid increase in popularity of extracapsular cataract extraction may predispose the eye to postoperative bacterial infections by introducing viable organisms through the additional instrumentation and irrigation necessary for the extracapsular technique. Lens protein released into the aqueous humor of the anterio...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(89)80034-x
更新日期：1989-11-01 00:00:00
abstract：:Retinal pigment epithelial (RPE) cell-mediated extracellular matrix contraction is believed to contribute to developing proliferative vitreoretinopathy. It has been shown that platelet-derived growth factor (PDGF) and its intracellular signaling pathway, including mitogen-activated protein kinase (MAPK) and phosphatid...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.08.014
更新日期：2006-03-01 00:00:00
abstract：:Aldose reductase (AR) is implicated in some of the disabling complications of diabetes, including neuropathy, retinopathy and cataracts. Our studies are aimed at further clarifying the role of AR in diabetes and facilitating the design of new classes of potent, specific AR inhibitors by gaining an understanding of the...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(89)90048-1
更新日期：1989-09-01 00:00:00
abstract：:Axial-length and refraction measurements are presented for the lid-sutured rhesus monkey at 6-month intervals during the first 1.5 years of life. The experimental data are fitted to an exponential growth theory allowing the calculation of time constants, apparent time origins, and correlation coefficients for 10 eyes ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(86)90043-6
更新日期：1986-06-01 00:00:00
abstract：:Crystallin-bound non-tryptophan fluorescence and protein cross-linking were studied in chronic galactosemia. Fluorescence (excitation/emission--370/440 nm) was significantly higher in galactosemic rats compared to controls (P less than 0.001). Accumulation of fluorescence was significantly reduced both in water solubl...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90153-l
更新日期：1990-10-01 00:00:00
abstract：:The signal transduction pathways initiated by Ca(2+)-mobilizing agonists, such as prostaglandin F(2alpha)(PGF(2alpha)) and carbachol (CCh), leading to activation of cytosolic phospholipase A(2)(cPLA(2)) and arachidonic acid (AA) release in a wide variety of tissues remain obscure. To further define the role of protein...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.0991
更新日期：2001-05-01 00:00:00
abstract：:The purpose of this study was to examine the effects of myopia-inducing and myopia recovery conditions on the scleral biomechanics of enucleated eyes of young chicks. Enucleated eyes from 5-day old chicks, with fiducial markers attached at 5 locations on the external sclera, were placed in a custom-built chamber fille...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.07.004
更新日期：2014-10-01 00:00:00
abstract：:Bombina variegata 8 (Bv8), also known as prokineticin-2 (PK-2), is a potent pro-angiogenic factor. However, its role in retinal neovascularization (RNV) remains unknown. In this study, we explored the role of Bv8 in the pathogenesis of RNV. We found that the expression of Bv8 was significantly increased in two differe...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2020.107993
更新日期：2020-04-01 00:00:00
abstract：:The Purkinje cell degeneration (pcd) mutant mouse rapidly loses cerebellar Purkinje cells and about 50% of its retinal photoreceptor cells at between 3 and 5 weeks of age, and thereafter slowly loses the remaining photoreceptor cells during the first year of life. An ultrastructural study of the developing photorecept...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(92)90019-o
更新日期：1992-05-01 00:00:00
abstract：PURPOSE:To investigate the potential protective effect of novel G protein coupled estrogen receptor (GPER1) against the neurotoxicity induced by NMDA in the mouse retina. METHODS:We induce retinal ganglion cells (RGCs) toxic injury through intravitreal injection of NMDA or acute ocular hypertension (AOH) induced by an...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2019.107826
更新日期：2019-12-01 00:00:00
abstract：:Several studies have suggested that antioxidants retard the process of cataractogenesis by scavenging free oxygen radicals. The present study sought to assess the efficacy of the antioxidant acetyl-L-carnitine (ALCAR) in preventing selenite-induced cataractogenesis in an experimental setting. The first, in vitro phase...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.07.009
更新日期：2006-12-01 00:00:00
abstract：:Research over the past two decades has shown that the growth of young eyes is guided by vision. If near- or far-sightedness is artificially imposed by spectacle lenses, eyes of primates and chicks compensate by changing their rate of elongation, thereby growing back to the pre-lens optical condition. Little is known a...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1999.0813
更新日期：2000-04-01 00:00:00
abstract：:We sequenced selected peptides of alligator rhodopsin that accounted for about half of the total protein. These sequences were confirmed when the total primary structure of alligator rhodopsin was deduced from the cDNA sequence. Differences in the amino-terminal region, compared to that of bovine rhodopsin, account fo...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(05)80051-x
更新日期：1995-11-01 00:00:00
abstract：:Following the identification of potent, orally active inhibitors of aldose reductase, the next challenge comes in demonstrating clinical utility in the treatment of diabetic complications. It is not feasible to conduct pivotal studies in all indications within the same trial and neuropathy evolved as the lead indicati...
journal_title：Experimental eye research
pub_type： 临床试验,杂志文章,评审
doi：10.1016/0014-4835(90)90103-2
更新日期：1990-06-01 00:00:00
abstract：:Two low-Ca2+-requiring proteases (calpain I) and one high-Ca2+-requiring protease (calpain II) have been separated from the cytosol of rat retina by DEAE-cellulose column chromatography. Calpain I was half-maximally activated at 3 microM free Ca2+ and fully activated at 10 microM free Ca2+. Half-maximal activation of ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(85)90098-3
更新日期：1985-07-01 00:00:00
abstract：:The purpose of these experiments was to develop a hypothesis to explain activation of m-calpain in cataractogenesis observed in rodents. The in vitro model used to study m-calpain activation was to correlate breakdown of the 'reporter' protein alpha-crystallin with the appearance of activated m-calpain using protein s...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0234
更新日期：1997-04-01 00:00:00
abstract：:The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploitin...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.07.002
更新日期：2014-10-01 00:00:00
abstract：:Cell lines derived from the lens generally fail to maintain synthesis of crystallins in long-term culture. Here we demonstrate that the N/N1003A line of undifferentiated lens epithelial cells, derived from a newborn rabbit, does not produce detectable levels of alpha-, beta- or gamma-crystallin transcripts, yet is cap...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(89)90026-2
更新日期：1989-01-01 00:00:00
abstract：:Previous studies in the laboratory have shown that platelet-activating factor (PAF), a potent inflammatory mediator that accumulates rapidly in the cornea after an injury, stimulates the expression of urokinase (uPA) and matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9). Tissue inhibitors of MMPs (TIMPs) and plasminog...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.1135
更新日期：2002-03-01 00:00:00
abstract：:The purpose of this study was to determine the aqueous levels and pharmacokinetics of topical fluconazole 0.2% upon single and multiple drop applications. Forty-nine patients undergoing cataract surgery were given topical fluconazole 0.2%. They either received single drop or a loading dose of 1 drop per 5 min for 20 m...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2000.0936
更新日期：2001-02-01 00:00:00
abstract：:The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand alpha 2-Macroglobulin (alpha(2)M) was examined in tissues from human donor eyes of normal, diabetic and sickle cell disease subjects. Streptavidin alkaline phosphatase immunohistochemistry was performed with a mouse ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2010.05.017
更新日期：2010-08-01 00:00:00
abstract：:Myopia is the most common form of refractive eye disease, and the prevalence is increasing rapidly worldwide. However, the key metabolic alterations in individuals with high myopia are not understood clearly, and serum biomarkers remain to be determined. The objectives of this study were to identify serum biomarkers a...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2019.107737
更新日期：2019-09-01 00:00:00
abstract：:A newly-developed fibre-optic sensor (wavelength of 670 nm) was used to measure the index gradient in 16 human lenses ranging in age from 38 to 78 years. Two of these lenses had nuclear cataract. The refractive index, calculated from the proportion of reflected light at the sensor/sample interface, appeared to increas...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(05)80097-1
更新日期：1995-04-01 00:00:00
abstract：:As wounds in stratified epithelia close, the numbers of cells at the leading edge of migration decreases. It is not known whether cells at the leading edge are continually replaced or whether some retain their position at the leading edge over time. Replication-deficient adenovirus carrying the green fluorescent prote...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2001.1115
更新日期：2002-02-01 00:00:00
abstract：:Hypoxia inducible factor (HIF) regulates expression of over 60 genes by binding to hypoxia response elements (HRE) located upstream of the transcriptional start sites. Many genes encoding proteins involved in iron transport and homeostasis are regulated by HIF. Expression of iron handling proteins can also be translat...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.05.010
更新日期：2014-08-01 00:00:00
abstract：:Multidrug resistance associated protein (MRP) is a major family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify if the role of efflux transporters. MRP-2 is a major homologue of MRP family a...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.08.015
更新日期：2007-01-01 00:00:00
abstract：:When 15-day-old developing chick embryos were administered hydrocortisone hemisuccinate sodium (HC:0.25 mumol per egg) the concentration of glucose in both the aqueous humor and the vitreous body began to increase significantly after 3 hr and reached 24.4 +/- 0.3 mM and 22.3 +/- 0.9 mM, respectively, at 48 hr. Thereaf...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(89)80050-8
更新日期：1989-10-01 00:00:00
abstract：:Gene therapy has been proposed as a feasible strategy for RGC survival and optic nerve regeneration. Some preclinical and clinical studies revealed intraocular inflammation after intravitreal injection of adeno-associated virus (AAV) by slit-lamp or indirect ophthalmoscope. Here we evaluate the longitudinal profile of...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2020.107955
更新日期：2020-04-01 00:00:00
