Effect of retrobulbar prostaglandin analog injection on orbital fat in rats.

PURPOSE: Periorbital fat atrophy is a known side effect of topical prostaglandin analogs (PA). This side effect may have implications in the treatment of diseases like thyroid orbitopathy. In this in vivo study we aimed to evaluate the effects of retrobulbar injection of three different PAs on orbital fat. METHODS: Eighteen adult male Wistar-albino rats were divided into three groups of six animals. 0.1 ml of 0.03% bimatoprost, 0.005% latanoprost, or 0.005% travoprost was injected into the right orbits and saline was injected into the left orbits, as controls. Both orbits were exenterated after 3 weeks. Histological cross-sections were analyzed using ImageJ image analysis software. Intraconal adipocyte density was calculated. RESULTS: There was no significant difference in the adipocyte density between the PA injected orbits and the control side in each of the three groups. When calculations from all three groups were analyzed together, again the difference in the adipocyte density between the PA injected orbits and the control side was not significant. CONCLUSION: No significant fat atrophy was noted in this rat model three weeks after retrobulbar injection of PAs. To evaluate retrobulbar injection of PA as a potential therapy for orbital diseases with fat proliferation, in vivo studies in different animal models, higher concentrations of PA, or longer follow-up duration are required.

Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

The effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% at a tertiary glaucoma center.

PURPOSE: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center. METHODS: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use. RESULTS: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from - 1.6 ± 3.5 to - 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of - 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan-Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4). CONCLUSION: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention.

[Neuroprotective properties of latanoprost]. / Neiroprotektornye svoistva latanoprosta.

Glaucoma is the main cause of irreversible blindness in the world. Latanoprost - an ester prodrug of prostaglandin F2α (PGF2α) - was the first prostaglandin analogue used to treat glaucoma. The review shows that latanoprost possesses direct neuroprotective properties such as blocking the entry of calcium ions into neurons and inhibiting the action of caspase-3, inhibiting the activity of cyclooxygenase and activation of polypeptide 2B1 (OATP2B1) and Klotho protein. It is emphasized that when the drug is instilled into the eye, the concentration of the drug inside the vitreous body is twice as high as what is required to ensure the survival of retinal ganglion cells.

[Structure/function/treatment in glaucoma: progress over the last 10 years]. / Struktur/Funktion/Behandlung beim Glaukom: Fortschritt in den letzten 10 Jahren.

Since the 1990s several so-called landmark studies were carried out, which played an important role in the management of glaucoma patients due to their multicenter, randomized and masked structure. The Ocular Hypertension Treatment Study (OHTS) and the Collaborative Initial Treatment Glaucoma Study (CIGTS) and their follow-up studies are especially important in the conservative glaucoma management and in the evaluation of structure and function. The OHTS examined if lowering of the intraocular pressure (IOP) treatment reduces the progression from ocular hypertension to primary open angle glaucoma and what risk factors influence the progression. The CIGTS examined the progression of glaucoma in patients treated either with pharmacotherapy or with surgery. The recent studies, the United Kingdom Glaucoma Treatment Study (UKGTS) and Glaucoma Automated Test Evaluation (GATE) investigated the influence of treatment with latanoprost on the development of visual field defects and examination of different screening tests in glaucoma, respectively. The OHTS provided results that justify prophylactic treatment as well as watchful waiting. The results of CIGTS showed that under certain conditions surgical treatment of a newly discovered glaucoma can be recommended for moderate to advanced glaucoma. In the UKGTS treatment with latanoprost reduced the intraocular pressure and also the progression of visual field defects in beginning and moderate glaucoma damage. The GATE study found no clear-cut advantage of screening examinations, with cost effectiveness and without a substantial proportion of diagnoses being missed.

Puberty attainment and reproductive performance of yearling Bos indicus-influenced heifers after two sequential treatments with progesterone.

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P4) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen.

Protection of 6-OHDA neurotoxicity by PGF2α through FP-ERK-Nrf2 signaling in SH-SY5Y cells.

6-Hydroxydopamine (6-OHDA) is a neurotoxin that destroy dopaminergic neurons and widely used to establish animal models of Parkinson's disease. Prostaglandins (PGs) are involved in various cellular processes, including the damage and repair of neuronal cells. However, the function of PGF2α in neuronal cells remains unclear. In this study, we investigated the effects of PGF2α against 6-OHDA-mediated toxicity in human neuroblastoma SH-SY5Y cells and elucidated its underlying molecular mechanism. When the cells were treated with 6-OHDA (50 µM) for 6 h, the expression levels of PGF2α synthetic enzymes; cyclooxygenase-2 and aldo-keto reductase 1C3 as PGF2α synthase were enhanced in an incubation-time-dependent manner. In addition, the production of PGF2α was increased in 6-OHDA-treated cells. Fluprostenol, a PGF2α receptor (FP) agonist (500 nM), suppressed 6-OHDA-induced cell death by decreasing the production of reactive oxygen species (ROS) and increasing the expression of the anti-oxidant genes. These fluprostenol-mediated effects were inhibited by co-treatment with AL8810, an FP receptor antagonist (1 µM) or transfection with FP siRNA (20 nM). Moreover, 6-OHDA-induced phosphorylation of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase family, was inhibited by co-incubation with AL8810. Furthermore, fluprostenol itself enhanced ERK phosphorylation and further elevated the 6-OHDA-induced phosphorylation of ERK. In addition, 6-OHDA induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), activating anti-oxidant gene expression, was repressed by co-culturing with AL8810. These results indicate that PGF2α suppressed 6-OHDA-induced neuronal cell death by enhancing anti-oxidant gene expression via the FP receptor-ERK-Nrf2 signaling. Thus, FP receptor is a potential target for inhibition of ROS-mediated neuronal cell death.

Advances in medical therapy for glaucoma.

PURPOSE OF REVIEW: To discuss a new class of medication that has recently become available for the treatment of glaucoma; as well as share insights into developments in glaucoma medicine administration which has the potential to revolutionize medical therapy for glaucoma. RECENT FINDINGS: Newly available eye drops, netarsudil 0.02% and latanoprostene bunod 0.024%, are improving aqueous outflow through the conventional outflow tract. Other new developments in medical glaucoma are focused on alternative methods for sustained glaucoma medication delivery. SUMMARY: Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need of glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.

Heterocromia de íris: uma revisão das condições que podem afetar a pigmentação iridiana / Heterochromia: a review of conditions that may affect iris pigmentation

RESUMO A íris é responsável pela cor dos olhos. Ela ainda realiza o controle da quantidade de luz que penetra no olho pela pupila. Variações nos genes de cada indivíduo, além da quantidade e da qualidade de melanina na íris, determinam a cor dos olhos. A heterocromia é caracterizada por diferenças na coloração da íris de um mesmo indivíduo, sendo, na maioria das vezes, benigna. Existem basicamente três tipos de heterocromia de íris: central, setorial e completa. A heterocromia de íris pode ter como causa alterações genéticas e congênitas, relacionadas ou não a síndromes específicas, como a de Sturge-Weber, a de Waardenburg, a de Parry-Romberg e a de Horner congênita. Há também causas adquiridas, como doenças ou lesões, trauma ocular e corpos estranhos intraoculares, uso de certas medicações tópicas, siderose ocular, irites ou uveítes como a síndrome uveítica de Fuchs, dentre outras. Diante de um paciente com heterocromia de íris, deve-se entender o contexto e o curso clínico desse sinal, pois pode se tratar de uma alteração de pigmentação benigna ou existir uma doença base em curso, que requer terapêutica específica. Este artigo de revisão de literatura visa abordar as principais etiologias relacionadas à heterocromia de íris, além de discorrer sobre a anatomia e a fisiologia da coloração iridiana e sobre a fisiopatologia de suas possíveis alterações.

ABSTRACT The iris is responsible for eye color and controls the amount of light that enters the eye through the pupil. Variation in each individual's genes, besides the quantity and quality of melanin in the iris, determine eye color. Heterochromia is characterized by different colors of irises in the same individual, and it is benign in most cases. There are basically three types of heterochromia: central, partial and complete. Heterochromia can be caused by genetic and congenital alterations, which may or may not be related to specific conditions, such as Sturge-Weber syndrome, Waardenburg syndrome, Parry-Romberg syndrome and congenital Horner syndrome. It may be associated to acquired causes like diseases or injuries, such as eye trauma and intraocular foreign bodies, use of some topical medications, ocular siderosis, iritis or uveitis, such as Fuchs´ uveitis, among others. When assessing a patient with heterochromia, one must understand the context and clinical course of this signal, since it may be a benign pigmentation disorder or there may be an underlying disease, which requires specific therapy. This literature review article was set out to address the main etiologies related to heterochromia, in addition to describing the anatomy and physiology of the iris color and the pathophysiology of possible alterations.

Contribution of FP receptors in M1 macrophage polarization via IL-10-regulated nuclear translocation of NF-κB p65.

Macrophages are the effector immune cells with plasticity to differentiate as M1 (classically activated) and M2 (alternatively activated) phenotypes. Prostaglandins (PGs) have various important roles and are involved in the regulation of macrophage activation. However, the role of PGF2α in macrophage activation remains unclear. We investigated the role of PGF2α receptor (FP)-mediated signaling in the M1 macrophage polarization using murine macrophage RAW264.7 cells. Stimulation with lipopolysaccharide (LPS) + interferon (IFN)-γ increased the mRNA expression of the M1 macrophage markers such as inducible nitric oxide synthase, tumor necrosis factor-α, and CD11c. Pre-treatment with AL8810, an FP receptor antagonist, further enhanced the expression of these genes. In contrast, treatment with fluprostenol, an FP receptor agonist, decreased the LPS + IFN-γ-induced expression of M1 markers. LPS-induced M1 macrophage polarization was dependent on the activation of NF-κB p65. Treatment with IκB kinase ß inhibitor reduced AL8810-induced mRNA expression of the M1 markers. Stimulation with LPS + IFN-γ increased the expression of IL-10. Pre-treatment with AL8810 lowered LPS + IFN-γ-induced IL-10 expression, and further enhanced LPS + IFN-γ-stimulated nuclear translocation of NF-κB p65. In contrast, co-treatment with IL-10 reversed AL8810-induced nuclear translocation of NF-κB p65. These results indicate that the FP receptor signaling was involved in the control of M1 polarization of macrophages via IL-10-regulated nuclear translocation of NF-κB p65.

Effects of the Selective EP2 Receptor Agonist Omidenepag on Adipocyte Differentiation in 3T3-L1 Cells.

Purpose: We aimed at comparing the effects of omidenepag (OMD) with those of prostaglandin F (FP) receptor agonists (FP agonists) on adipogenesis in mouse 3T3-L1 cells. Methods: To evaluate the agonistic activities of OMD against the mouse EP2 (mEP2) receptor, we determined cAMP contents in mEP2 receptor-expressing CHO cells by using radioimmunoassays. Overall, 3T3-L1 cells were cultured in differentiation medium for 10 days and adipocyte differentiation was assessed according to Oil Red O-stained cell areas. Changes in expression levels of the adipogenic transcription factors Pparg, Cebpa, and Cebpb were determined by using real-time polymerase chain reaction (PCR). OMD at 0.1, 1, 10, and 40 µmol/L, latanoprost free acid (LAT-A) at 0.1 µmol/L, or prostaglandin F2α (PGF2α), at 0.1 µmol/L were added to cell culture media during adipogenesis. Oil Red O-stained areas and expression patterns of transcription factor targets of OMD or FP agonists were compared with those of untreated controls. Results: The 50% effective concentration (EC50) of OMD against the mEP2 receptor was 3.9 nmol/L. Accumulations of Oil Red O-stained lipid droplets were observed inside control cells on day 10. LAT-A and PGF2α significantly inhibited the accumulation of lipid droplets; however, OMD had no effect on this process even at concentrations up to 40 µmol/L. LAT-A and PGF2α significantly suppressed Pparg, Cebpa, and Cebpb gene expression levels during adipocyte differentiation. Conversely, OMD had no obvious effects on the expression levels of these genes. Conclusions: A selective EP2 receptor agonist, OMD, did not affect the adipocyte differentiation in 3T3-L1 cells, whereas FP agonists significantly inhibited this process.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

PTGFR activation promotes the expression of PTGS-2 and growth factors via activation of the PKC signaling pathway in bovine endometrial epithelial cells.

The endometrium of domestic animals has a remarkable capacity to self-repair. Prostaglandin F2α (PGF2α) is one of the major prostaglandins secreted from the endometrium. The role of PGF2α in endometrial repair, however, is still unknown. In the present study, it was investigated whether prostaglandin F2α receptor (PTGFR) activation could induce expression of prostaglandin-endoperoxide synthase 2 (PTGS-2) and growth factors associated with endometrial repair via activation of protein kinase C (PKC) signaling in endometrial epithelial cells (bEECs) of cattle. Results of the present study indicated that the treatment with the PTGFR agonist, fluprostenol, resulted in an increase in abundance of proteins for PTGS-2, vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), transforming growth factor beta 1 (TGF-ß1), and interleukin-8 (IL-8). The increased abundances of these proteins were suppressed by the treatment with the PTGFR antagonist, AL8810.Furthermore, fluprostenol treatment also induced PKC phosphorylation. Subsequently, treatment with AL8810 inhibited the fluprostenol-induced PKC phosphorylation. Additionally, treatment with the PKC inhibitor, chelerythrine, reduced the fluprostenol-induced increase in the relative abundance of VEGF, CTGF, TGF-ß1, and IL-8 mRNA in bEECs. Taken together, these results suggest that PTGFR activation may induce endometrial repair by upregulating PTGS-2 gene expression and stimulating VEGF, CTGF, TGF-ß1, and IL-8 gene expression via activation of the PKC signaling pathway.

New Drugs 2018, part 3.

This article discusses eight drugs recently approved by the FDA, including their indications and contraindications, precautions, dosage, and nursing considerations. The article also includes summary charts on 14 recently approved antineoplastic drugs and four drugs approved for rare disorders.

Treatment merits of Latanoprost/Thymoquinone - Encapsulated liposome for glaucomatus rabbits.

Elevation of the intraocular pressure (IOP) is recognized as a risk factor for glaucoma development. Latanoprost (LAT) is a prostaglandin analog used to reduce the (IOP). Thymoquinone (TQ) is a major bioactive ingredient of Nigella sativa. The aim of this study was to develop novel liposomal drug carriers for ocular delivery of LAT, TQ and a mixture of them to investigate their IOP lowering efficacy upon subconjunctival injection in glaucoma-induced rabbit's eye. The aim of the present work extends also to study the effect of the different liposome formulations on the aqueous humor oxidative stress. Liposome samples were prepared using thin film hydration method. The physiochemical properties of the prepared drugs were characterized. The IOP was recorded for 70 rabbits using Schiotz-tonometer. Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) activities and total antioxidant activity of the aqueous humor were estimated. Fourier transform infrared and differential scanning calorimetric studies confirmed the interaction between the drug and the vesicles, which resulted in high drug encapsulation efficiency ≥88%. The size of the prepared liposomes was less than 10 µm which make them suitable in ophthalmic applications. The sustained effect was achieved by liposome samples of Lip (LAT) and Lip (LAT + TQ) which were able to reduce the IOP significantly up to 84 h. Morever, the treatment of glaucomatous rabbits with liposome formulations containing TQ in their preparation [Lip (TQ) and Lip (LAT + TQ)] greatly improved the ocular tissue-induced histopathological lesions. None of the prepared liposome formulations succeeded to improve the glaucoma-induced oxidative stress damage.

Effect of consecutive re-synchronization protocols on pregnancy rate in buffalo (Bubalus bubalis) heifers out of the breeding season.

The combined effect of six consecutive timed artificial inseminations (TAIs) on pregnancy rates, following two different synchronization protocols on buffalo heifers, over a period of seven months typically characterized by low breeding performances, were investigated in this study. A total of 2189 TAIs were performed on 1463 buffalo heifers within a large buffalo farm in the south of Italy. Individual animals were allowed to undergo synchronization protocol (either a slightly modified Ovsynch or Progesterone treatment) and TAI until establishment of pregnancy or else for not more than six consecutive times. Semen of seven proven bulls was used throughout the study, which was carried out from March to September of the same year. Therefore, other than the effect given by consecutive TAIs over time, a monthly and a seasonal effect could also be tested, once the entire period was split into a Low Breeding Season (LBS) from March to June, and a Transition to Breeding Season (TBS) from July to September. From the data recorded in this study and the statistical analysis performed, it can be stated that the two protocols for the synchronization of ovulation were similar in efficiency in determining pregnancies with an overall fertility rate of 89.4% when the comparison was run both on a monthly basis or when months were grouped into two different seasons. In addition, an average of 1.83 AI/pregnancy was reported, slightly higher for the Ovsynch when compared to the Progesterone protocol: 1.91 vs 1.70, respectively. Finally, when considering the number of progressive synchronization treatments implemented over time as covariate, neither Ovsynch nor Progesterone treatment significantly affected pregnancy rates following the first of the six synchronization sessions. However, repeating the synchronization procedure, the progesterone based protocol resulted in significantly higher probability of success in terms of established pregnancies during the second and third re-synchronization sessions.

The prostaglandin E2 receptor PTGER2 and prostaglandin F2α receptor PTGFR mediate oviductal glycoprotein 1 expression in bovine oviductal epithelial cells.

Oviductal glycoprotein 1 (OVGP1), an oviductin, is involved in the maintenance of sperm viability and motility and contributes to sperm capacitation in the oviduct. In this study, the regulatory effects exerted by prostaglandin E2 (PGE2) and F2α (PGF2α) on OVGP1 expression via their corresponding receptors in bovine oviductal epithelial cells (BOECs) were investigated. BOECs were cultured in vitro, and their expression of receptors of PGE2 (PTGER1, PTGER2, PTGER3, and PTGER4) and PGF2α (PTGFR) was measured using RT-qPCR. Ca2+ concentration was determined with a fluorescence-based method and cAMP was quantified by enzyme-linked immunosorbent assays to verify activation of PTGER2 and PTGFR by their corresponding agonists in these cells. OVGP1 mRNA and protein expression was measured using RT-qPCR and western blotting, respectively, following PTGER2 and PTGFR agonist-induced activation. PTGER1, PTGER2, PTGER4, and PTGFR were found to be present in BOECs; however, PTGER3 expression was not detected. OVGP1 expression was significantly promoted by 10-6 M butaprost (a PTGER2 agonist) and decreased by 10-6 M fluprostenol (a PTGFR agonist). In addition, 3 µM H-89 (a PKA inhibitor) and 3 µM U0126 (an ERK inhibitor) effectively inhibited PGE2-induced upregulation of OVGP1, and 5 µM chelerythrine chloride (a PKC inhibitor) and 3 µM U0126 negated OVGP1 downregulation by PGF2α. In conclusion, this study demonstrates that OVGP1 expression in BOECs is enhanced by PGE2 via PTGER2-cAMP-PKA signaling, and reduced by PGF2α through the PTGFR-Ca2+-PKC pathway.

The Glaucoma Italian Pediatric Study (GIPSy): 1-Year Results.

PURPOSE: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. PATIENTS AND METHODS: Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results. RESULTS: A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events. CONCLUSION: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.