Showing papers in "Current Eye Research in 2005"
TL;DR: While AMPs are recognized as essential components of natural host innate immunity against microbial challenge, their usefulness as a new class of antimicrobial drugs still remains to be proven.
Abstract: Purpose: Antimicrobial peptides (AMPs) are an essential part of innate immunity that evolved in most living organisms over 2.6 billion years to combat microbial challenge. These small cationic peptides are multifunctional as effectors of innate immunity on skin and mucosal surfaces and have demonstrated direct antimicrobial activity against various bacteria, viruses, fungi, and parasites. This review summarizes their progress to date as commercial antimicrobial drugs for topical and systemic indications. Methods: Literature review. Results: Despite numerous clinical trials, no modified AMP has obtained Food & Drug Administration approval yet for any topical or systemic medical indications. Conclusions: While AMPs are recognized as essential components of natural host innate immunity against microbial challenge, their usefulness as a new class of antimicrobial drugs still remains to be proven.
665 citations
TL;DR: There was significant initial corneal flattening in the ortho-k group but no significant relationships were found between changes in Corneal power and changes in axial length and vitreous chamber depth and the relationships with changes of refractive errors, AL and VCD.
Abstract: Purpose: Myopia is a common ocular disorder, and progression of myopia in children is of increasing concern. Modern overnight orthokeratology (ortho-k) is effective for myopic reduction and has been claimed to be effective in slowing the progression of myopia (myopic control) in children, although scientific evidence for this has been lacking. This 2 year pilot study was conducted to determine whether ortho-k can effectively reduce and control myopia in children. Methods: We monitored the growth of axial length (AL) and vitreous chamber depth (VCD) in 35 children (7–12 years of age), undergoing ortho-k treatment and compared the rates of change with 35 children wearing single-vision spectacles from an earlier study (control). For the ortho-k subjects, we also determined the changes in corneal curvature and the relationships with changes of refractive errors, AL and VCD. Results: The baseline spherical equivalent refractive errors (SER), the AL, and VCD of the ortho-k and control subjects were not statisti...
478 citations
TL;DR: Idiopathic anterior uveitis, Behçet disease, and VKH syndrome are the most common entities of uve arthritis in China and ocular toxoplasmosis, ocular histoplasmotic, and birdshot retinochoroidopathy are less common or absent in China
Abstract: Purpose: To address the clinical pattern and characteristics of uveitis in a tertiary center for uveitis in China and compare the similarity and difference in the distribution of uveitis entities between China and other countries Methods: A retrospective study was performed on the patients with uveitis referred to the Zhongshan Ophthalmic Center from January 1996 to December 2003 The clinical data including category, etiology, gender, and the age of the patients at uveitis presentation were analyzed and compared with studies published previously from other countries Results: There were 902 male and 850 female patients in our series The mean age of these patients at uveitis presentation was 338 ± 165 years Anterior uveitis (800, 456%) was the most common anatomical entity, followed by panuveitis (727, 415%), posterior uveitis (119, 68%), and intermediate uveitis (106, 61%) Further classification with the etiology criteria revealed 16 entities in anterior uveitis, with idiopathic anterior uveiti
284 citations
TL;DR: Corneal and conjunctival epithelia express LL-37 as part of mucosal innate immunity to protect against bacterial and viral ocular infections.
Abstract: Purpose: This study determined whether LL-37 (cathelicidin) is expressed by conjunctival and corneal epithelia as part of ocular host defense The antimicrobial activity of LL-37 was also assessed
233 citations
TL;DR: This paper focuses on dispersing dimyristoyl phosphatidylcholine liposomes in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels, which are a common contact lens material, and shows that the p- HEMA gels loaded with liposome are transparent and that these gels release drugs for a period of about 8 days.
Abstract: Approximately 90% of all ophthalmic drug formulations are now applied as eyedrops. Although eyedrops are convenient and well accepted by patients, about 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage. A major fraction of the drug eventually enters the bloodstream and may cause side effects. To reduce drug loss and side effects, it is proposed to encapsulate the ophthalmic drug formulations in liposomes and to disperse the drug-laden liposomes in the lens material. Upon insertion into the eye, the liposome-laden lens will slowly release the drug into the pre-lens (the film between the air and the lens) and the post-lens (the film between the cornea and the lens) tear films and thus provide drug delivery for extended periods of time. This paper focuses on dispersing dimyristoyl phosphatidylcholine (DMPC) liposomes in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels, which are a common contact lens material. The results of this study show that the p-HEMA gels loaded with liposomes are transparent and that these gels release drugs for a period of about 8 days. Contact lenses made of particle-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading.
159 citations
TL;DR: These steroids show similar effects on the retinal vasculature suggesting their potential usefulness in treating diabetic retinopathy, and the potential to use glucocorticoids to restore vascular barrier properties in the retina is examined.
Abstract: Loss of blood-retinal barrier (BRB) integrity and vascular permeability characterizes diabetic retinopathy, and new therapies to reverse or prevent vascular permeability are needed to treat this debilitating disease. Glucocorticoids are currently under investigation for use as a local therapeutic treatment for diabetic retinopathy. This review examines the changes that occur to barrier properties in diabetic retinopathy and the potential to use glucocorticoids to restore vascular barrier properties in the retina. Glucocorticoids are useful in preserving the integrity of the blood-brain barrier in the treatment of brain tumors, and these steroids show similar effects on the retinal vasculature suggesting their potential usefulness in treating diabetic retinopathy. Recent progress has been made toward the goal of elucidating the precise mechanism underlying the protective effects of glucocorticoids on the retinal vasculature. Glucocorticoids may act by both suppressing inflammation and by directly affecting the endothelial cells by regulating phosphorylation, organization, and content of tight junction proteins. Further work will advance our understanding of glucocorticoid regulation of barrier properties allowing the ultimate goal of developing a specific and safe therapy to treat or prevent loss of the blood-neural barrier in a number of diseases, including brain tumors and diabetic retinopathy.
118 citations
TL;DR: A single intravitreal 200 ng dose of EPO appears to have a protective effect on RGC viability in an in vivo rat model of glaucoma.
Abstract: Purpose: The aim of this pilot study was to evaluate the potential neuroprotective effect of an intravitreal injection of erythropoietin (EPO) on retinal ganglion cell (RGC) preservation in an episcleral vessel cautery–induced rat model of glaucoma. Methods: The animals were randomly assigned into an unoperated control group (n = 11) and three experimental groups: episcleral vessel cautery only (EVC: n = 4), episcleral vessel cautery with intravitreal normal saline injection (EVC-NS; n = 5), and episcleral vessel cautery with intravitreal EPO treatment (EVC-EPO; n = 9). The intravitreal injections were limited to 5 μl containing either normal saline alone or 200 ng of EPO in normal saline administered immediately after the cautery procedure. RGCs were labeled retrogradely by FluoroGold neuron tracer 5 to 7 days prior to the collection of eyes at day 21 and counted in whole flat-mounted retinas with fluorescence microscopy. Results: Compared to the RGC counts in retinal specimens from unoperated control ra...
83 citations
TL;DR: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.
Abstract: Purpose: Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. Methods: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. Results: Adenosine triggered A3AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 ± 11 nM, p < 0.01) and by another A3AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 ± 0.8 mmHg at 25-μ M droplet concentration (n = 10, p < 0.005). Conclusions: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.
67 citations
TL;DR: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.
Abstract: Purpose: To describe MUC5AC alterations and the ocular surface disorder in atopic patients with or without corneal ulcers. Methods: Atopic patients' eyes were divided into two groups according to the presence and absence of corneal ulceration. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface and conjunctival impression cytology and brush cytology. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and quantitative real-time PCR for MUC5AC mRNA expression. The differences related to the tear function and ocular surface examination parameters between patients with and without corneal ulceration and healthy control subjects were studied. In addition, the differences of the study parameters related to ocular surface epithelial health and inflammatory status between patient eyes with at...
64 citations
TL;DR: Inhibition of proliferative regulators such as PCNA and/or activation of apoptotic executors such as caspase-3 may serve as therapeutic targets to halt progression of proliferationative retinal disorders.
Abstract: Purpose: To assess the incidence of cell proliferation and apoptosis in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and macular pucker (MP) and to further investigate the potential involvement of key executors of apoptosis. Methods: Epiretinal membranes were obtained from the eyes of 23 patients who underwent vitrectomy surgery for recurrent retinal detachment due to PVR (n = 16), traction retinal detachment due to PDR (n = 5), and macular pucker (n = 2). Cell proliferation was evaluated by Ki-67 and PCNA (proliferation cell nuclear antigen) immunostaining. Apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transfrase-dUTP-nick end labeling). The expression of caspase-3 and PARP (poly-ADP-ribose-polymerase) was detected using antibodies against activated caspase-3 and p85 fragment of PARP. Cytokeratin and activated caspase-3/PARP, GFAP (glial fibrillary acidic protein) and activated caspase-3/PARP double staining were used to...
63 citations
TL;DR: Aqueous extract of OS possesses potential anticataract activity against selenite-induced experimental cataractogenesis and was supported by restoration of the antioxidant defense system and inhibition of protein insolubilization of rat lenses as well.
Abstract: Purpose: To study the effect of Ocimum sanctum (OS) on selenite-induced morphological and biochemical changes in isolated rat lenses as well as on cataract incidence in rat pups. Methods: Transparent rat lenses were divided into normal, selenite-only, and four treated groups. Selenite-only and treated group lenses were subjected to oxidative stress in vitro by incorporating sodium selenite (100 μ M) in the culture medium. The effect of OS (70, 140, 280, and 560 μ g/ml) was studied on the levels of reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS) in selenite-challenged lenses. The lowest concentration of OS offering significant modulation on these two parameters was determined. Subsequently, the effect of prior and cotreatment with the lowest effective concentration of OS was studied on TBARS, GSH, and on lens antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), and glutathione-S-transferase (GST). Changes in lens protein profi...
TL;DR: In this paper, the role of adherence and matrix metalloproteinases (MMPs) in growth patterns of major fungal pathogens in cornea was investigated, and positive correlations among the number of binding conidia, degree of inflammation, and level of MMP-9 were found in all infected corneas.
Abstract: Purpose: To investigate the roles of adherence and matrix metalloproteinases (MMPs) in growth patterns of major fungal pathogens in cornea. Methods: Ninety-six eyes in 96 rabbits were equally divided into four groups receiving inoculation of fungal conidia of Aspergillus fumigatus, Candida albicans, Fusarium solani, and Penicillium citreo-viride, respectively, to induce fungal keratitis. Corneas in each group were obtained at 2, 8, 16 hr, and 1, 2, 3, 5, and 8 days after inoculation and were subjected to scanning electron microscopy, histopathological examination, and gelatin zymography. Eight saline-inoculated eyes in another eight rabbits served as controls. Results: All eyes in the fungus-inoculated groups developed fungal keratitis. The binding of conidia to corneal epithelial basement membrane was initiated earlier in the A. fumigatus and C. albicans groups than in the F. solani and P. citreo-viride groups. Destruction of basement membrane began at 1 to 3 days. Histopathologically, infiltration of inflammatory cells was more evident in the A. fumigatus and C. albicans groups than the F. solani and P. citreo-viride groups at 3 days. The hyphae of A. fumigatus and C. albicans traversed the cornea in a plane perpendicular to the stromal lamellae, whereas the hyphae of F. solani and P. citreo-viride lay parallel to the corneal lamellae. MMP-9 and MMP-2 were found in all infected corneas. At 3 days, proteolysis was most active; the level of MMP-9 was higher in the A. fumigatus and C. albicans groups than in the F. solani and P. citreo-viride groups. There were positive correlations among the number of binding conidia, degree of inflammation, and level of MMP-9 (p < 0.05). Conclusions. The adherence ability, chemotaxis to neutrophils, and MMP-9 expression level differ in eyes with different fungal pathogens, which may contribute to the different growth patterns of fungi in cornea.
TL;DR: The model developed here can serve as a useful tool to develop a more precise understanding of various issues related to tears and also evaluate the effect of various parameters on the tear volume.
Abstract: Purpose: In this paper we develop a mathematical model that can predict the steady-state tear film thickness and the dynamic tear film thickness and the solute concentration after instillation of a solute-laden fluid in the eye. Methods: The mathematical model developed in this paper is based on a balance between the inflow and outflow of tears into the tear film. It incorporates a tear drainage model and a model that relates the tear film thickness to the meniscus radius of curvature. To predict the solute concentrations, the tear balance is coupled with the solute balance. The differential equations for the unsteady balances are solved numerically. Results: The model predicts that the tear film thickness depends on a number of physiological factors, such as rates of tear production and evaporation, geometry and modulus of the canaliculi, and surface tension and viscosity of tears, and varies from about 3 to 15 μ m. The model also predicts that the drainage time for an instilled volume of 15 μ l is 1283 ...
TL;DR: High levels of GSSG and TBARS indicate high oxidative stress, as well as the decrease in the ratio of GSH/GSSG, which suggest a role for oxidation stress in the pathogenesis and the progression of PEX syndrome.
Abstract: Purpose:To investigate the oxidative status of the aqueous humor of patients with pseudoexfoliation (PEX) syndrome. Methods: Aqueous humor samples obtained during cataract surgery of patients with PEX syndrome and normal age-matched control subjects were examined for changes in the levels of glutathione (GSH), glutathione disulfide (GSSG), and TBA reactive species (TBARS), products of lipid peroxidation. GSH, GSSG, and TBARS were determined by specific fluorescent assays. Results: Compared to normal controls, PEX syndrome aqueous humor samples showed a decrease of up to 28% of GSH concentration, and GSSG was increased up to 23%. The ratio of GSH/GSSG was 1.7-fold decreased in PEX syndrome samples. TBARS levels were increased by 100% in the PEX aqueous humor samples as compared to the controls. Conclusions: High levels of GSSG and TBARS indicate high oxidative stress, as well as the decrease in the ratio of GSH/GSSG. Our findings suggest a role for oxidation stress in the pathogenesis and the progression o...
TL;DR: The episcleral vasculature shows a specialized morphology with absence of capillaries, numerous arteriovenous anastomoses, a muscle-rich venous network, and intense innervation by vasodilative and vasoconstrictive nerves, which might allow regulation of blood flow and volume in the episCleral vessels and Voigt's capillary for thermoregulation and modulation of episclal venous pressure and thereby outflow facility.
Abstract: Purpose: To investigate the primate episcleral vasculature and its innervation with respect to morphological specializations. Methods: Serial sections of the anterior episclera of 8 monkey eyes and 20 human eyes were investigated enzyme- and immunohistochemically using antibodies against smooth-muscle α -actin (SMA), neurofilament, synaptophysin, substance P (SP), calcitonin gene-related peptide (CGRP), vesicular acetylcholine transporter (VACHT), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), vesicular monoamine transporter II (VMAT II), as well as the NADPH-diaphorase reaction. Arteriovenous anastomoses (AVA) were quantified. Results: All episcleral vessels including veins showed intense staining for SMA. Capillary loops were only seen in the limbal arcades, not in the episclera itself. Instead, AVA connected the episcleral arteries with the veins, which formed an interlacing vascular network. In the monkey episclera, 4–6/mm2 AVA were found; in the human episcl...
TL;DR: P. aeruginosa triggers an innate immune response in HCECs, and NF-κ B and, to a lesser extent, the p38/JNK signal pathways are responsible for P. aerUGinosa–induced proinflammatory cytokine production in these cells.
Abstract: Purpose: We hypothesized that corneal epithelium plays a role in the innate immune response by sensing the presence of pathogens and providing signals that activate the corneal defense system. We sought to determine the mechanisms involved in the activation of the signaling pathways and subsequent production of proinflammatory cytokines in human corneal epithelial cells (HCECs) in response to Pseudomonas aeruginosa infection. Methods: Epithelial monolayers of a telomerase-immortalized HCEC line, HUCL, and primary cultures of HCECs were exposed to P. aeruginosa (PA01 strain) with or without the presence of the NF-κ B inhibitor kamebakaurin, the p38 inhibitor SB203580, or the JNK inhibitor SP600125. Iκ B-α phosphorylation and degradation and p38 and JNK phosphorylation were assessed at different time points by Western blot analysis. Interleukin (IL)-6, IL-8, and TNF-α levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: Ex...
TL;DR: Approaches to the induction of protective responses by altering or enhancing both innate and adaptive immunity, using novel vaccines specifically tested in models of HSV infections of the eye, such as recombinant viral vaccine vectors and DNA vaccines are detailed in this review.
Abstract: One of the hallmarks of herpes simplex virus (HSV) infection is the establishment of a lifelong latent infection accompanied by periods of recurrent disease Primary HSV infections or repeated clinical recurrences do not elicit immune responses capable of completely preventing recurrences of endogenous virus It is therefore questionable if vaccination approaches that seek to mimic the immune response to natural infection will reduce infection or disease due to an exogenous viral challenge Approaches to the induction of protective responses by altering or enhancing both innate and adaptive immunity, using novel vaccines specifically tested in models of HSV infections of the eye, such as recombinant viral vaccine vectors and DNA vaccines, are detailed in this review
TL;DR: Surgical approach modifies risk factors of proliferative vitreoretinopathy, and should be taken into account to improve the models for predicting it.
Abstract: Purpose: To asses risk factors of proliferative vitreoretinopathy (PVR) and a model for predicting it. Methods: Observational, case-control. 335 patients with non-complicated retinal detachment (RD) were included: 134 developed PVR (Cases); 201 patients did not (Controls). Risk factors for PVR were identified by multivariate analysis. Influence of variables was assayed according to the surgical approach. By logistic regression analysis a model to predict the risk of developing PVR and odds ratio (OR) values for each clinical factor were estimated. Results: Risk was higher in patients > 70 years and with intraocular pressure lower than 14 (OR: 3.84; CI 95%: 2.04–7.30) and in retinal breaks larger than “1 clock hour” (OR: 2.54; CI: 1.28–5.05), extended retinal detachments (OR: 4.01; CI: 1.98–8.10) and reinterventions (OR: 1.55; CI: 1.14–9.22). Scleral surgery also was a risk factor (OR: 3.89; CI: 2.12–7.14) and aphakia/pseudophakia when scleral surgery is performed (OR: 3.33; CI: 1.54–7.22). A model to pred...
TL;DR: Observations suggest that 22:6n-3 is incorporated directly into retinal phospholipids without further metabolism, whereas 20:5n- 3 and 22:5 n-3 are metabolically active precursors for synthesis of VLCFAs.
Abstract: The objective of this study was to determine if 20:5n-3 or 22:6n-3 is the primary precursor of very-long-chain fatty acids (VLCFAs; C24-C36) synthesized in retina. Rats were fed semisynthetic, nutritionally complete diet containing 20% (w/w) fat with 3% (w/w) of 22:6n-3. After 6 weeks feeding, the vitreal fluid of each eye was injected with [3H]20:5n-3 or [3H]22:6n-3. Rats were then maintained under constant light (330 lux) or dark conditions for 48 hr. After 48 hr in vivo metabolism, the amount of label present in individual fatty acids was determined in major phospholipids in retina. For [3H]22:6n-3, 90% of total incorporation remained in 22:6n-3, whereas for [3H]20:5n-3 the label was actively incorporated into pentaenoic and hexaenoic VLCFAs up to 34 carbon chain length. 22:5n-3 derived from [3H]20:5n-3 was among the most highly labeled fatty acids. These observations suggest that 22:6n-3 is incorporated directly into retinal phospholipids without further metabolism, whereas 20:5n-3 and 22:5n-3 are metabolically active precursors for synthesis of VLCFAs.
TL;DR: The duration of light was a significant factor in ICG toxicity and ICG needs to be used with caution as it decreases the mitochondrial dehydrogenase activity and increases the DNA synthesis in retinal cells, markers for cell toxicity and dysfunction.
Abstract: Purpose: To evaluate the toxicity of indocyanine green (ICG) in combination with light. Methods: Human retinal pigment epithelial cells (ARPE-19) and rat neurosensory retinal cells (R28) were treated with four different concentrations of ICG in combination with light exposure. Cell viability, mitochondrial function, and DNA synthesis were measured. Results: All concentrations of ICG with 10 min of light exposure caused a significant decrease in mitochondrial dehydrogenase activity in R28 and ARPE-19 cells. ICG without light exposure did not decrease mitochondrial dehydrogenase activity. In both cell lines, [3H]thymidine incorporation was increased when treated with ICG with or without light. R28 cells did not show any significant decrease in cell viability. Conclusions: The duration of light was a significant factor in ICG toxicity. ICG needs to be used with caution as it decreases the mitochondrial dehydrogenase activity and increases the DNA synthesis in retinal cells, markers for cell toxicity and dysf...
TL;DR: LPR in the conjunctiva is dominantly mediated by cellular immune responses, whereas EPR inThe conjunctivas is putatively mediated by humoral immune responses.
Abstract: Purpose: Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. However, it remains unclear whether early-phase reactio...
TL;DR: A mathematical model is developed based on the experimental findings of Doane, according to which the muscle action during a blink drives the tear drainage, which agrees with various physiological experiments, at least qualitatively.
Abstract: Purpose: Tear drainage through the canaliculi has been extensively studied experimentally but there has been no attempt to develop a quantitative model for this process. In this paper, we develop a...
TL;DR: Fusarium and Aspergillus are the most frequent pathogenic organisms in causing fungal keratitis, whereas other species of fungi can also cause corneal infection.
Abstract: Purpose: To investigate the spectrum of fungal species causing keratitis and to test antifungal drug susceptibility to each isolate using Etest. Methods: Microbial cultures were performed for patients who were clinically diagnosed with fungal keratitis between September 2002 and July 2004. Modified slide culture was established to identify the fungal species of the isolates. Etest (AB BIODISK, Solna, Sweden) was applied to determine the antifungal agent susceptibility of each isolate to itraconazole, fluconazole, and amphotericin B in vitro, respectively. Results: Among 73 eyes of 73 patients with clinical diagnosis of fungal keratitis, 61 strains of fungi were isolated from 61 eyes. The rate of positive culture was 81.3% of all cases. The spectrum of fungal species involved: 58 (95.1%) isolates of filamentous fungi, including the two most common genera—Fusarium (n = 33, 54.1%) and Aspergillus (n = 9, 14.8%),—followed by 16 (26.2%) isolates of other genera of filamentous fungi such as Alternaria (n = 3, 4...
TL;DR: L-Alanine, the chosen model substrate, was actively transported by Na+-dependent, neutral amino acid exchanger ASCT1, which was identified and functionally characterized on rPCEC cells and rabbit cornea.
Abstract: Purpose: The aim of this study was to investigate the presence of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit primary corneal epithelial cell culture and rabbit cornea. Methods: Uptake studies were carried out on rabbit primary corneal epithelial culture (rPCEC) cells using 12-well plates. Transport studies were conducted with isolated rabbit corneas at 34°C. Uptake and transport of L-alanine was determined at various concentrations. Inhibition studies were conducted in presence of various L- and D-amino acids, metabolic inhibitors like ouabain and sodium azide, and in the absence of sodium to delineate the functional characteristics of L-alanine uptake and transport. Reverse transcription–polymerase chain reaction (RT-PCR) was performed on total RNA harvested from rabbit cornea and rPCEC cells for identification of ASCT1. Results: Uptake of L-Ala was found to be saturable with a Km of 0.71 mM and a Vmax value of 0.84 μ moles min−1 mg−1 protein. Uptake was independent of pH and energy...
TL;DR: This study provides data on the mean spherical equivalent, the degree of astigmatism, and incidence of anisometropia at different gestational ages for term babies and preterm babies with retinopathy of prematurity.
Abstract: Purpose: The refractive status of premature infants is not well studied. This study was done to find the norms of refractive error in newborns at different gestational ages. Methods: One thousand two hundred three (1203) eyes were examined for refractive error by streak retinoscopy within the first week of life between June 2001 and September 2002. Tropicamide eye drops (0.8%) with phenylephrine 0.5% were used to achieve cycloplegia and mydriasis. The refractive error was measured in the vertical and horizontal meridia in both eyes and was recorded to the nearest dioptre (D). The neonates were grouped in five gestational age groups ranging from 24 weeks to 43 weeks. Results: Extremely preterm babies were found to be myopic with a mean MSE (mean spherical equivalent) of −4.86 D. The MSE was found to progressively decrease (become less myopic) with increasing gestation and was +2.4 D at term. Astigmatism of more than 1 D spherical equivalent was seen in 67.8% of the eyes examined. Among newborns with > 1 D ...
TL;DR: In contrast to most differentiated epithelial cells, the differentiated RPE cells can be transfected at high and prolonged levels with selected lipoplexes.
Abstract: Purpose: The purpose of this study was to investigate the extent, duration, and direction of transgene expression after nonviral gene transfer to differentiated retinal pigment epithelial (RPE) cells. Methods: Polarized human RPE cells (ARPE-19) were transfected with nonviral vectors [DOTAP/DOPE with and without protamine sulfate (PS), DOTAP, PEI (polyethyleneimine), DHP-12] using secreted alkaline phosphatase (SEAP) as a reporter gene. Cellular uptake was studied by flow cytometry. Results: Up to 80-fold differences were observed in the peak reporter gene expression. The highest peak levels and the longest lifetime of SEAP expression (> 69 days) were obtained with DOTAP/DOPE/PS/pDNA complexes. With PEI, higher expression was seen to the apical side than to the basolateral side. Conclusions: In contrast to most differentiated epithelial cells, the differentiated RPE cells can be transfected at high and prolonged levels with selected lipoplexes.
TL;DR: Local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy because of the potential for local application of receptors with a wide range of ligands to prove more useful than those binding few or antagonistic ligands.
Abstract: Purpose: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy. Methods: C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy. Results: A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR). Conclusions: sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therap...
TL;DR: Human chymase causes the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of the migration of corneal epithelial cells.
Abstract: Purpose: We investigated the in vitro effects of human mast cell chymase on corneal epithelial cells. Methods: Human corneal epithelial cells were incubated with human chymase at activity levels that were likely to exist in the tears of patients with vernal keratoconjunctivitis. Results: Incubation of chymase resulted in a decrease of barrier function of corneal epithelium. Occludin protein was cleaved by chymase. In the wound assay, incubation with chymase resulted in an inhibition of cell migration. Conclusion: Human chymase causes the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of the migration of corneal epithelial cells.
TL;DR: Latanoprost has remarkable effects inhibiting cultured corneal stromal cells on 3H-thymidine,3h-leucine,3H-uridine,2H-proline uptakes and cellular migration, which indicates that latanop frost may induce the morphological and biochemical changes in cultured cornesal cells.
Abstract: Purpose: Latanoprost reduces intraocular pressure mainly by enhancing uveoscleral outflow that may be involved in the decreased of extracellular matrixes such as collagens. However, the effect of latanoprost on corneal stromal cells is not well understood. In the current study, we investigated the changes of cultured porcine corneal stromal cells upon exposure to latanoprost. Methods: Porcine corneal stromal cells were acquired from primary culture and maintained in fetal bovine serum–containing medium. Cells were estimated on 3H-thymidine,3H-leucine,3H-uridine,3H-proline uptakes and migration. Dead and living cells were estimated with MTT assay. The changes of type 1 collagen and fibronectin proteins were detected by means of immunofluorescent staining and Western blot assay. Intracellular free Ca2 + ([Ca2 +]i) mobility was studied by spectrofluorophotometer after loading with fura-2-AM. Results: Latanoprost has remarkable effects inhibiting cultured corneal stromal cells on 3H-thymidine,3H-leucine,3H-ur...
TL;DR: Diode laser TSCPC appears to be a safe and effective procedure for the treatment of uncontrolled glaucoma secondary to penetrating keratoplasty and visual acuity improved in two eyes and remained the same in the others.
Abstract: Purpose: To evaluate the effect and safety of diode laser transscleral cyclophotocoagulation (TSCPC) in eyes with refractory glaucoma after penetrating keratoplasty (PK). Methods: Diode laser TSCPC was performed on 32 eyes of 32 patients with secondary glaucoma after penetrating keratoplasty. The mean follow-up period was 11.4 ± 3.8 months (range, 6–20 months). The intraocular pressure (IOP), number of glaucoma medications, graft status, side effects, and complications of the procedure were all recorded during the follow-up period. The treatment was considered successful if after one cyclodiode treatment the IOP could be reduced to or below 22 mmHg with or without medication. The success rate of the diode laser treatment was analyzed by the Kaplan-Meier survival analysis method during the 6th and 12th months of the follow-up period and the end of the study. The decrease in drug requirement after laser treatment was analyzed by the Wilcoxon nonparametric test. Statistical significance was set at p < 0.05. ...