{"title":"Evolution of Cellular Inclusions in Bietti's Crystalline Dystrophy.","authors":"Emiko Furusato, J Douglas Cameron, Chi-Chao Chan","doi":"10.4137/OED.S2821","DOIUrl":"https://doi.org/10.4137/OED.S2821","url":null,"abstract":"<p><p>Bietti's crystalline dystrophy (BCD) consists of small, yellow-white, glistening intraretinal crystals in the posterior pole, tapetoretinal degeneration with atrophy of the retinal pigment epithelium (RPE) and \"sclerosis\" of the choroid; in addition, sparking yellow crystals in the superficial marginal cornea are also found in many patients. BCD is inherited as an autosomal-recessive trait (4q35-tel) and usually has its onset in the third decade of life. This review focuses on the ultrastructure of cellular crystals and lipid inclusions of BCD.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2010 2","pages":"9-15"},"PeriodicalIF":0.0,"publicationDate":"2010-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29704706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poorna Abeysiri, Nicholas R Johnston, Anthony C B Molteno
{"title":"The use of topical tacrolimus 0.1% skin ointment for anterior segment conditions: a case series.","authors":"Poorna Abeysiri, Nicholas R Johnston, Anthony C B Molteno","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tacrolimus (FK 506) is a macrolactam derivative with immunomodulatory and anti-inflammatory activity. Topical tacrolimus 0.03% has been used for inflammatory conditions of the anterior segment. This article adds to the literature on the off-license application of tacrolimus ointment, by describing the safe and effective use of the higher strength of 0.1% topical tacrolimus skin ointment in four patients. To our knowledge this is the first report of topical tacrolimus 0.1% ointment applied to the conjunctival sac for the treatment of atopic keratoconjunctivitis, vernal keratoconjunctivitis and the post-operative management of trabeculectomy and graft rejection in steroid responders. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2010-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spectral Domain OCT Documented Resolution of Pseudophakic Cystoid Macular Edema after Intravitreal Triamcinolone.","authors":"Ravi K Murthy, Kakarla V Chalam","doi":"10.4137/oed.s3671","DOIUrl":"10.4137/oed.s3671","url":null,"abstract":"<p><p>Cystoid macular edema (CME) is an important cause of visual loss after cataract surgery. Treatment is usually with topical anti-inflammatory agents, with anti-vascular endothelial growth factor agents and steroids used intravitreally in resistant cases. Even though time-domain Stratus OCT can quantify the macular thickness, it cannot prognosticate visual outcomes due to the poor resolution of images, especially the outer segment-inner segment junction. Spectral-domain OCT (SD-OCT) by its ability to acquire large number of images in a short span of time provides high resolution cross-sectional images of the retina, which not only highlights the underlying pathological changes, but in addition can prognosticate visual recovery. We describe pre and post SD-OCT features of a case of refractory CME who was treated with intravitreal triamcinolone actetonide. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2010-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W. Fan, X. Li, W. Wang, J. Mo, H. Kaplan, N. Cooper
{"title":"Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice","authors":"W. Fan, X. Li, W. Wang, J. Mo, H. Kaplan, N. Cooper","doi":"10.1177/117917211000200005","DOIUrl":"https://doi.org/10.1177/117917211000200005","url":null,"abstract":"Purpose The DBA/2J (D2) mouse carries mutations in two of its genes, Tyrp1 and Gpnmb. These alterations result in the development of an immune response in the iris, leading to iris atrophy and pigment dispersion. The development of elevated intraocular pressure (IOP) in this model of glaucoma is considered to be a significant factor leading to the death of retinal ganglion cells (RGCs). Changes in gene expression in the retina have already been correlated with the appearance of elevated IOP in the D2 mouse. The purpose of the present study was to determine if any changes in gene expression occur prior to the development of IOP. Methods The IOP was measured monthly using a rebound tonometer in D2 and age-matched C57/BL6 (B6) mice (normal controls). D2 animals with normal IOP at 2 and 4 M were used. In addition, mice at the age of 6–7 M were included to look for any trends in gene expression that might develop during the progression of the disease. Separate RNA samples were prepared from each of three individual retinas for each age, and gene expression profiles were determined with the aid of mouse oligonucleotide arrays (Agilent). A subset of genes was examined with the aid of real-time PCR. Immunocytochemistry was used to visualize changes in the retina for some of the gene-products. Results Four hundred and thirteen oligonucleotide probes were differentially expressed in the retinas of 4 M versus 2 M old D2 mice. The most significantly up-regulated genes (181) were associated with immune responses including interferon signaling, the complement system and the antigen presentation pathway, whereas the down-regulated genes (232) were linked to pathways related to cell death and known neurological diseases/disorders. These particular changes were not revealed in the age-matched B6 mice. By 6 M, when IOP started to increase in many of the D2 mice, more robust changes of these same genes were observed. Changes in the levels of selected genes, representative of different functions/pathways, were validated with RT-PCR, and changes in glial responses were visualized in the retina with immunocytochemistry. Conclusions The results showed that the expression of genes related to the immune response and acute stress were altered independently of the development of elevated IOP, and indicated early involvement of the immune system in the onset of the disease. The later development of elevated IOP, observed in this animal model, was coincident with continued changes in expression of genes observed at earlier time points. Further studies are warranted to identify the roles of specific genes identified here with respect to the death of the RGCs.","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 1","pages":"23 - 41"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/117917211000200005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65349927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid Transporters on the Cornea: Possible Antiviral Agents Against Ocular HSV-1 Infections","authors":"K. Suresh, Xiadong Zhu, Talluri S. Ravi, A. Mitra","doi":"10.1177/117917211000200002","DOIUrl":"https://doi.org/10.1177/117917211000200002","url":null,"abstract":"The aim of this study was to characterize the affinity and permeability patterns of the amino acid ester prodrugs of acyclovir (ACV), L-alanine-ACV (AACV), L-serine-ACV (SACV), L-serine-succinate-ACV (SSACV) and L-cysteine-ACV (CACV) on rabbit primary corneal epithelial cell culture (rPCEC) and on rabbit cornea. Amino acid prodrugs of acyclovir, AACV, SACV, SSACV and CACV were synthesized in our laboratory. Chemical hydrolysis in aqueous buffer, enzymatic hydrolysis in corneal homogenates and transport across freshly excised rabbit cornea of these prodrugs were studied. SSACV inhibited the uptake of [3H] L-alanine on rPCEC and across the intact rabbit cornea. Lineweaver-Burk plot transformation revealed competitive inhibition between L-alanine and SSACV. In corneal tissue homogenate, the half lives of SSACV, SACV and CACV (t1/2) were observed to be 3.5 ± 0.4, 9.2 ± 0.6 and 1.8 ± 0.1 hr respectively, whereas AACV was readily converted to the active parent drug acyclovir exhibiting complete degradation before 5 min. Interestingly translocation of SACV across cornea was inhibited in the presence of 5 mM arginine (~51%), a specific substrate for cationic transport system and in presence of BCH (~38%), a substrate specific for large neutral amino acid transport system (LAT) or cationic and neutral amino acid transport system (B0,+). SACV exhibited higher permeability across cornea along with excellent antiviral activity against herpes simplex virus (HSV-1) and varicella-zoster virus (VZV) in comparison to ACV. Recognition by multiple transporters, stability in corneal homogenate and changes in physico-chemical properties contributed to the increased permeability of SACV across cornea.","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 1","pages":"43 - 56"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/117917211000200002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65350342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of Cellular Inclusions in Bietti's Crystalline Dystrophy","authors":"E. Furusato, J. D. Cameron, C. Chan","doi":"10.1177/117917211000200003","DOIUrl":"https://doi.org/10.1177/117917211000200003","url":null,"abstract":"Bietti's crystalline dystrophy (BCD) consists of small, yellow-white, glistening intraretinal crystals in the posterior pole, tapetoretinal degeneration with atrophy of the retinal pigment epithelium (RPE) and “sclerosis” of the choroid; in addition, sparking yellow crystals in the superficial marginal cornea are also found in many patients. BCD is inherited as an autosomal-recessive trait (4q35-tel) and usually has its onset in the third decade of life. This review focuses on the ultrastructure of cellular crystals and lipid inclusions of BCD.","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/117917211000200003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65350354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jared E Knickelbein, Simon C Watkins, Paul G McMenamin, Robert L Hendricks
{"title":"Stratification of Antigen-presenting Cells within the Normal Cornea.","authors":"Jared E Knickelbein, Simon C Watkins, Paul G McMenamin, Robert L Hendricks","doi":"10.4137/oed.s2813","DOIUrl":"https://doi.org/10.4137/oed.s2813","url":null,"abstract":"<p><p>The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c(+) dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 µm in length and traverse up 20 µm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c(-) CD11b(+) putative macrophages that express low levels of MHC class II. Finally, MHC class II(-)pCD11c(-) CD11b(+) cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"1 ","pages":"45-54"},"PeriodicalIF":0.0,"publicationDate":"2009-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/oed.s2813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28956972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anterior Chamber-Associated Immune Deviation (ACAID): An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?","authors":"Robert E Cone, Roshan Pais","doi":"10.4137/oed.s2858","DOIUrl":"https://doi.org/10.4137/oed.s2858","url":null,"abstract":"<p><p>The \"immune privilege\" that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID)(a) is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80(+) monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"1 ","pages":"33-40"},"PeriodicalIF":0.0,"publicationDate":"2009-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/oed.s2858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retinal ganglion cell loss in diabetes associated with elevated homocysteine.","authors":"Kenneth S Shindler","doi":"10.4137/oed.s3417","DOIUrl":"https://doi.org/10.4137/oed.s3417","url":null,"abstract":"<p><p>A number of studies have suggested that homocysteine may be a contributing factor to development of retinopathy in diabetic patients based on observed correlations between elevated homocysteine levels and the presence of retinopathy. The significance of such a correlation remains to be determined, and potential mechanisms by which homocysteine might induce retinopathy have not been well characterized. Ganapathy and colleagues1 used mutant mice that have endogenously elevated homocysteine levels due to heterozygous deletion of the cystathionine-β-synthase gene to examine changes in retinal pathology following induction of diabetes. Their finding that elevated homocysteine levels hastens loss of cells in the retinal ganglion cell layer suggests that toxicity to ganglion cells may warrant further investigation as a potential mechanism of homocysteine enhanced susceptibility to diabetic retinopathy. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"1 ","pages":"41-3"},"PeriodicalIF":0.0,"publicationDate":"2009-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/oed.s3417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravi S Talluri, Ripal Gaudana, Sudharshan Hariharan, Ashim K Mitra
{"title":"Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing.","authors":"Ravi S Talluri, Ripal Gaudana, Sudharshan Hariharan, Ashim K Mitra","doi":"10.4137/oed.s2857","DOIUrl":"https://doi.org/10.4137/oed.s2857","url":null,"abstract":"<p><strong>Objective: </strong>To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration.</p><p><strong>Results: </strong>Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4-5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV.</p><p><strong>Conclusions: </strong>LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"1 ","pages":"21-31"},"PeriodicalIF":0.0,"publicationDate":"2009-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/oed.s2857","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}