latanoprost and Inflammation

There is debate concerning whether the use of Latanoprost in early postoperative period of cataract surgery and in glaucoma patients with uveitis as it may aggravate the inflammation and results in macular edema (ME), because of blood-ocular barrier disruption. However, there is no solid evidence for disruption of blood-ocular barrier with Latanoprost and aggravation of uveitis or ME formation. Similar to pseudophakic ME, the imaging ME in cases claimed to be secondary to Latanoprost is greater than clinical ME, happens mostly in complicated surgeries, and the vast majority resolve within weeks to months with using a non-steroidal anti-inflammatory drug. The current literature suggests that Latanoprost can be used in patients with uveitis and early after cataract surgery with or without concomitant topical non-steroidal anti-inflammatory drugs that are currently used by many ophthalmologists as a preventive measure for ME even in non-glaucoma uncomplicated cataract surgeries.

Topics: Antihypertensive Agents; Humans; Inflammation; Latanoprost; Macular Edema; Uveitis

A new class of hydrogen sulfide (H(2)S)-donating hybrids combined with pharmacologically active compounds is presented in this article. The pharmacological profiles of some hybrid lead compounds in the areas of inflammation, H(2)S-donating diclofenac (ACS 15); cardiovascular, H(2)S-donating aspirin (ACS 14); urology, H(2)S-donating sildenafil (ACS 6); and neurodegenerative, H(2)S-donating latanoprost (ACS 67) for glaucoma treatment and H(2)S-donating levodopa (ACS 84) for Parkinson's disease, are described. The new H(2)S-releasing hybrids demonstrate remarkable improvement in activity and tolerability as compared with the related parent compounds, suggesting an active pharmacological role for H(2)S. Finally the mechanism(s) of action of glutathione-dependent and independent, and of gas (H(2)S) release (spontaneous or enzymatic) and its implications for clinical pharmacology perspectives will be also discussed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Humans; Hydrogen Sulfide; Inflammation; Latanoprost; Levodopa; Prodrugs; Prostaglandins F, Synthetic

The role of the intestitium (the extracellular and extravascular tissue) with regard to transcapillary fluid balance and control of interstitial fluid volume has normally been considered to be a "passive controller".. This review is based upon literature collected through the authors' own studies and through Medline searches.. Recent studies, however, indicate that the connective tissue cells can actively modulate physical properties of the interstitial matrix, so that it becomes an "active" participant in transcapillary fluid exchange and thereby interstitial fluid homeostasis. The beta 1-integrin system seems to provide a common pathway by which the cells can raise and lower interstitial fluid pressure and thereby regulate the tissue fluid volume.. Experiments in which a new anti-inflammatory agent (alpha-trinositol), platelet-derived growth factor (PDGF), and a prostagladin F2 alpha-analog (latanoprost) modulate interstitial fluid pressure and oedema generation in acute inflammation, suggest that the extracellular matrix can be a target for pharmacological intervention during inflammatory processes.

Topics: Acute Disease; Anti-Inflammatory Agents; Antihypertensive Agents; Capillary Permeability; CD18 Antigens; Cytoskeleton; Edema; Extracellular Space; Fibroblasts; Humans; Hydrostatic Pressure; Inflammation; Integrins; Latanoprost; Models, Biological; Osmotic Pressure; Platelet-Derived Growth Factor; Prostaglandins F, Synthetic; Water-Electrolyte Balance

The purpose of this study is to investigate the effects of latanoprost on the secretion of cytokines and chemokines from meibomian gland epithelial cells, and to evaluate the modulation of peroxisome proliferator-activated receptor γ (PPAR-γ) and retinoid X receptor α (RXR-α) during latanoprost-induced inflammation. Mouse meibomian gland epithelial cells were cultured in proliferation and differentiation medium, respectively. Cells were exposed to latanoprost, rosiglitazone (PPAR-γ agonist), or LG100268 (RXR-α agonist), respectively. The expression of IL-6, IL-1β, TNF-α, MMP-9, MCP-1, and CCL-5 were detected by real-time PCR and ELISA. The effect of latanoprost, rosiglitazone, LG100268, and inflammatory cytokines on the differentiation of meibocyte were evaluated by related gene expression and lipid staining. The expression of Keratin-1, 6, 17 protein was detected by western immunoblotting. The results showed that the above cytokines could be induced by latanoprost in meibomian gland epithelial cells. LG100268 and rosiglitazone could inhibit the production of IL-6 and TNF-α induced by latanoprost, respectively. Latanoprost suppressed the expression of differentiation-related mRNA through a positive feedback loop by enhancement of COX-2 expression via FP receptor-activated ERK signaling. The expression of Keratin-17 was upregulated by rosiglitazone and suppressed by LG100268. The application of IL-6 and TNF-α showed negative effects on lipid accumulation in meibomian gland epithelial cells. These results demonstrated that latanoprost could induce inflammation and suppress differentiation of mouse meibomian gland epithelial cells. The activation of PPAR-γ and RXR-α showed an anti-inflammatory effect, showing a potential role to antagonize the effect of latanoprost eyedrops on meibomian gland epithelial cells.

Topics: Animals; Anti-Inflammatory Agents; Chemokines; Cyclooxygenase 2; Cytokines; Epithelial Cells; Inflammation; Interleukin-6; Keratin-1; Keratin-17; Latanoprost; Matrix Metalloproteinase 9; Meibomian Glands; Mice; Ophthalmic Solutions; PPAR gamma; Retinoid X Receptor alpha; RNA, Messenger; Rosiglitazone; Tumor Necrosis Factor-alpha

To investigate the side effects of preservative-free 0.005% latanoprost on the murine ocular surface.. We applied 0.005% latanoprost or vehicle in mice in two patterns for 14 to 28 days. Tear production was measured by phenol red cotton test, and corneal epithelial barrier function was assessed by Oregon-green-dextran (OGD) staining. Periodic acid-Schiff (PAS) staining was used to quantify conjunctival goblet cells (GCs). The expression of matrix metalloproteinase (MMP)-3 and -9, occludin-1 and zonula occludens (ZO)-1 in corneal epithelium was assessed by immunofluorescent staining and/or quantitative real-time PCR (qRT-PCR). Inflammation in conjunctiva was assessed by activation of P38 and NF-κB, infiltration of CD4+ T cells, and production inflammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-17A, and IL-13. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Cell viability assay was performed in human corneal epithelial cells.. Topical latanoprost treatment decreased tear production, induced conjunctival GC loss, disrupted the corneal epithelial barrier, and promoted cell apoptosis in the ocular surface. Topical latanoprost treatment increased the expression of MMP-3 and -9, and decreased the expression of ZO-1 and occludin-1 in the corneal epithelium. Topical application of latanoprost promoted activation of P38-NF-κB signaling and production of TNF-α and IL-1β in conjunctiva. Topical application of latanoprost increased CD4+ T cells infiltration, with increased production of IFN-γ and IL-17A and decreased production of IL-13 in conjunctiva.. 0.005% latanoprost induced dry eye-like ocular surface damage via promotion of inflammation in mice.

Topics: Animals; Antihypertensive Agents; Blotting, Western; Conjunctivitis; Cornea; Dry Eye Syndromes; Enzyme-Linked Immunosorbent Assay; Epithelium, Corneal; Female; Fluorescent Antibody Technique, Indirect; Humans; In Situ Nick-End Labeling; Inflammation; Latanoprost; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; NF-kappa B; Occludin; p38 Mitogen-Activated Protein Kinases; Preservatives, Pharmaceutical; Real-Time Polymerase Chain Reaction; Tears; Zonula Occludens-1 Protein

Many antiglaucoma eyedrops are reported to cause cystoid macular edema (CME) in aphakia and pseudophakia. We review 4 clinical and laboratory studies that compare the incidence of CME in early postoperative pseudophakia in eyes that received preserved latanoprost and timolol, nonpreserved timolol, and the preserved and nonpreserved vehicle for these drugs and looked at the morphological damage to cells and the changes in the indicators of cytokine and prostaglandin (PG) synthesis caused by latanoprost and timolol and the preservative benzalkonium chloride. Based on the findings of these studies, which indicate that the preservative causes increased synthesis of PGs and other substances and intensified postoperative inflammation, the term pseudophakic preservative maculopathy is proposed for CME caused by antiglaucoma eyedrops.

Topics: Aqueous Humor; Cataract Extraction; Humans; Incidence; Inflammation; Intraocular Pressure; Latanoprost; Macular Edema; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F, Synthetic; Pseudophakia; Timolol