Pub Date : 2011-07-25Print Date: 2011-01-01DOI: 10.4137/OED.S7300
Cameron Campbell Johnson
Purpose: To report a case of corneal melting in a patient with fornix foreshortening being treated with reformulated generic diclofenac.
Methods: Case report.
Results: An asymptomatic 76-year old man presented with central corneal melting while being treated with reformulated generic diclofenac. This formulation did not contain the vitamin E derivative, tocophersolan, which has been felt to contribute to corneal melting associated with generic diclofenac in the past. Other factors for corneal melting included multiple medication use and altered forniceal architecture, but did not include previous corneal or cataract surgery. Following discontinuation of the topical medications and temporary tarsorrhapy, the defect reepithelialized.
Conclusion: In patients with a compromised ocular surface, reformulated generic diclofenac has the potential to cause corneal melting without prior cataract or refractive surgery. Use should not be indiscriminate or without close supervision.
{"title":"Central corneal melting associated with reformulated generic diclofenac in a patient with inferior fornix foreshortening.","authors":"Cameron Campbell Johnson","doi":"10.4137/OED.S7300","DOIUrl":"https://doi.org/10.4137/OED.S7300","url":null,"abstract":"<p><strong>Purpose: </strong>To report a case of corneal melting in a patient with fornix foreshortening being treated with reformulated generic diclofenac.</p><p><strong>Methods: </strong>Case report.</p><p><strong>Results: </strong>An asymptomatic 76-year old man presented with central corneal melting while being treated with reformulated generic diclofenac. This formulation did not contain the vitamin E derivative, tocophersolan, which has been felt to contribute to corneal melting associated with generic diclofenac in the past. Other factors for corneal melting included multiple medication use and altered forniceal architecture, but did not include previous corneal or cataract surgery. Following discontinuation of the topical medications and temporary tarsorrhapy, the defect reepithelialized.</p><p><strong>Conclusion: </strong>In patients with a compromised ocular surface, reformulated generic diclofenac has the potential to cause corneal melting without prior cataract or refractive surgery. Use should not be indiscriminate or without close supervision.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"3 ","pages":"21-4"},"PeriodicalIF":0.0,"publicationDate":"2011-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S7300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585760","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}
Pub Date : 2011-03-20Print Date: 2011-01-01DOI: 10.4137/OED.S4102
S Khimdas, K L Visscher, C M L Hutnik
Objective: To outline the pharmacodynamics, efficacy and safety of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis.
Quality of evidence: MEDLINE database was searched to review recent pharmacodynamic and clinical studies evaluating besifloxacin and comparing besifloxacin to other topical antibiotics for ophthalmic use. Findings were limited to full-text articles from clinical journals in the English language.
Main message: Bacterial resistance is a common source for treatment failure in bacterial conjunctivis. Besifloxacin, a novel fourth generation synthetic fluoroquinolone is likely to show lower resistance rates due to its mechanism of action and its short-term use for ocular infections only (decreased systemic exposure). Besifloxacin displays improved pharmacodynamic properties compared to other commonly used fluoroquinolones and has shown to be efficacious and safe in clinical studies.
Conclusion: Besifloxacin ophthalmic suspension 0.6% provides safe and efficacious treatment for bacterial conjunctivitis. The factors leading to bacterial resistance are diminished, which allows besifloxacin to be a favorable treatment option.
{"title":"Besifloxacin ophthalmic suspension: emerging evidence of its therapeutic value in bacterial conjunctivitis.","authors":"S Khimdas, K L Visscher, C M L Hutnik","doi":"10.4137/OED.S4102","DOIUrl":"https://doi.org/10.4137/OED.S4102","url":null,"abstract":"<p><strong>Objective: </strong>To outline the pharmacodynamics, efficacy and safety of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis.</p><p><strong>Quality of evidence: </strong>MEDLINE database was searched to review recent pharmacodynamic and clinical studies evaluating besifloxacin and comparing besifloxacin to other topical antibiotics for ophthalmic use. Findings were limited to full-text articles from clinical journals in the English language.</p><p><strong>Main message: </strong>Bacterial resistance is a common source for treatment failure in bacterial conjunctivis. Besifloxacin, a novel fourth generation synthetic fluoroquinolone is likely to show lower resistance rates due to its mechanism of action and its short-term use for ocular infections only (decreased systemic exposure). Besifloxacin displays improved pharmacodynamic properties compared to other commonly used fluoroquinolones and has shown to be efficacious and safe in clinical studies.</p><p><strong>Conclusion: </strong>Besifloxacin ophthalmic suspension 0.6% provides safe and efficacious treatment for bacterial conjunctivitis. The factors leading to bacterial resistance are diminished, which allows besifloxacin to be a favorable treatment option.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"3 ","pages":"7-12"},"PeriodicalIF":0.0,"publicationDate":"2011-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S4102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585758","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}
Pub Date : 2011-03-16Print Date: 2011-01-01DOI: 10.4137/OED.S5985
Khalid Al Arfaj, Vandana Jain, Mohamed Hantera, Mohamed Wagih El-Deeb, Adel Al Rushod, Akshay G Nair, Roberto Pineda
Purpose: COMPARE THE EFFECTIVENESS OF PHOTOTHERAPEUTIC KERATECTOMY (PTK) IN TREATMENT CORNEAL DYSTROPHIES VERSUS SUPERFICIAL CORNEAL SCARS: visual outcomes, recurrence rate and safety profile.
Methods: PTK was performed in 51 eyes of 51 patients. Data regarding the indications for PTK, ablation depth, symptomatic relief, pre-and postoperative best spectacle-corrected visual acuity (BSCVA), spherical equivalent changes, recurrence and complications were analyzed. The indications for PTK in our study were classified into two categories - group A: patients with corneal dystrophies (n = 23) and the other group B (n = 28) with other indications.
Results: The average age of the patients was 47 years (±16.4). The mean follow up period was 15.16 months (±10.01 months). Post operatively, there were no significant complications. While the overall BSCVA in the patients improved from 20/41 (0.484) to 20/32 (0.645), group A showed improvement from 20/35 (0.561) to 20/29 (0.687), as compared to group B in which BSCVA improved from 20/47 (0.421) to 20/33 (0.611). The most common indication in group A was granular corneal dystrophy (n = 10) and the most common indication in group B was post traumatic/infectious corneal scar or opacity (n = 10). Eighty-six percent (n = 44) of all patients had alleviation of symptoms. Recurrence of symptoms was seen in 3 eyes of recurrent corneal erosions which required retreatment.
Conclusion: PTK is a safe and effective procedure. The outcome of this study suggests that PTK improves BSCVA. PTK appears to improve ocular surface health. Furthermore, PTK can be recommended to most patients with corneal dystrophies as a treatment modality prior to other more invasive procedure (viz. penetrating keratoplasty).
{"title":"Phototherapeutic keratectomy outcomes in superficial corneal opacities.","authors":"Khalid Al Arfaj, Vandana Jain, Mohamed Hantera, Mohamed Wagih El-Deeb, Adel Al Rushod, Akshay G Nair, Roberto Pineda","doi":"10.4137/OED.S5985","DOIUrl":"https://doi.org/10.4137/OED.S5985","url":null,"abstract":"<p><strong>Purpose: </strong>COMPARE THE EFFECTIVENESS OF PHOTOTHERAPEUTIC KERATECTOMY (PTK) IN TREATMENT CORNEAL DYSTROPHIES VERSUS SUPERFICIAL CORNEAL SCARS: visual outcomes, recurrence rate and safety profile.</p><p><strong>Methods: </strong>PTK was performed in 51 eyes of 51 patients. Data regarding the indications for PTK, ablation depth, symptomatic relief, pre-and postoperative best spectacle-corrected visual acuity (BSCVA), spherical equivalent changes, recurrence and complications were analyzed. The indications for PTK in our study were classified into two categories - group A: patients with corneal dystrophies (n = 23) and the other group B (n = 28) with other indications.</p><p><strong>Results: </strong>The average age of the patients was 47 years (±16.4). The mean follow up period was 15.16 months (±10.01 months). Post operatively, there were no significant complications. While the overall BSCVA in the patients improved from 20/41 (0.484) to 20/32 (0.645), group A showed improvement from 20/35 (0.561) to 20/29 (0.687), as compared to group B in which BSCVA improved from 20/47 (0.421) to 20/33 (0.611). The most common indication in group A was granular corneal dystrophy (n = 10) and the most common indication in group B was post traumatic/infectious corneal scar or opacity (n = 10). Eighty-six percent (n = 44) of all patients had alleviation of symptoms. Recurrence of symptoms was seen in 3 eyes of recurrent corneal erosions which required retreatment.</p><p><strong>Conclusion: </strong>PTK is a safe and effective procedure. The outcome of this study suggests that PTK improves BSCVA. PTK appears to improve ocular surface health. Furthermore, PTK can be recommended to most patients with corneal dystrophies as a treatment modality prior to other more invasive procedure (viz. penetrating keratoplasty).</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"3 ","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2011-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S5985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585757","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}
Pub Date : 2011-01-12Print Date: 2011-01-01DOI: 10.4137/OED.S4253
Clyde Schultz
Tafluprost is an FP receptor antagonist that has been shown in clinical studies in Europe and Japan to be extremely useful in treating elevated intraocular pressure and glaucoma. The drug is well tolerated and appears to be at least equal in effectiveness and perhaps superior to other protanoids for routine use comparison to be superior to other treatments for the elevated IOP as the side effects and other related symptomology appear to be less, while maintaining a level of pressure control for prolonged periods.
{"title":"Tafluprost for the reduction of interocular pressure in open angle glaucoma and ocular hypertension.","authors":"Clyde Schultz","doi":"10.4137/OED.S4253","DOIUrl":"https://doi.org/10.4137/OED.S4253","url":null,"abstract":"<p><p>Tafluprost is an FP receptor antagonist that has been shown in clinical studies in Europe and Japan to be extremely useful in treating elevated intraocular pressure and glaucoma. The drug is well tolerated and appears to be at least equal in effectiveness and perhaps superior to other protanoids for routine use comparison to be superior to other treatments for the elevated IOP as the side effects and other related symptomology appear to be less, while maintaining a level of pressure control for prolonged periods. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"3 ","pages":"13-9"},"PeriodicalIF":0.0,"publicationDate":"2011-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S4253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585759","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}
Pub Date : 2010-12-19Print Date: 2010-01-01DOI: 10.4137/OED.S4878
Adinoyi O Garba, Shaker A Mousa
Age- related Macular Degeneration (AMD) is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or "wet", AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD) and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF) is a key component in the pathogenesis of choroidal neo-vascularization (CNV), which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis), which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen), bevacizumab (Avastin; off-label use), and several other experimental agents. The advent of small interfering RNA (siRNA) has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD.
{"title":"Bevasiranib for the treatment of wet, age-related macular degeneration.","authors":"Adinoyi O Garba, Shaker A Mousa","doi":"10.4137/OED.S4878","DOIUrl":"https://doi.org/10.4137/OED.S4878","url":null,"abstract":"<p><p>Age- related Macular Degeneration (AMD) is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or \"wet\", AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD) and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF) is a key component in the pathogenesis of choroidal neo-vascularization (CNV), which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis), which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen), bevacizumab (Avastin; off-label use), and several other experimental agents. The advent of small interfering RNA (siRNA) has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"75-83"},"PeriodicalIF":0.0,"publicationDate":"2010-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S4878","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585756","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}
Pub Date : 2010-11-30Print Date: 2010-01-01DOI: 10.4137/OED.S5612
M Gupta, G Lascaratos, A Syrogiannis, L Esakowitz
Sarcoidosis is a multisystem granulomatous disease that may affect various organs. Nevertheless, involvement of the trigeminal nerve is exceedingly uncommon. This report presents a rare case of isolated bilateral trigeminal neuropathy presenting with neurotrophic corneal ulcers. The patient was treated with topical chloramphenicol and lubricants, as well as botulinum toxin injection to the upper eyelid to induce ptosis. Our case illustrates the importance of recognizing that bilateral corneal ulceration might be a manifestation of sarcoidosis. Physicians should be aware of this rare association, when treating sarcoidosis patients with eye related symptoms.
{"title":"Isolated bilateral trigeminal neuropathy in sarcoidosis presenting with neurotrophic corneal ulcers.","authors":"M Gupta, G Lascaratos, A Syrogiannis, L Esakowitz","doi":"10.4137/OED.S5612","DOIUrl":"https://doi.org/10.4137/OED.S5612","url":null,"abstract":"<p><p>Sarcoidosis is a multisystem granulomatous disease that may affect various organs. Nevertheless, involvement of the trigeminal nerve is exceedingly uncommon. This report presents a rare case of isolated bilateral trigeminal neuropathy presenting with neurotrophic corneal ulcers. The patient was treated with topical chloramphenicol and lubricants, as well as botulinum toxin injection to the upper eyelid to induce ptosis. Our case illustrates the importance of recognizing that bilateral corneal ulceration might be a manifestation of sarcoidosis. Physicians should be aware of this rare association, when treating sarcoidosis patients with eye related symptoms. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"69-73"},"PeriodicalIF":0.0,"publicationDate":"2010-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S5612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585755","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}
Pub Date : 2010-11-11Print Date: 2010-01-01DOI: 10.4137/OED.S6113
Robert E Cone, Subhasis Chattopadhyay, Roshan Pais, Sourojit Bhowmick, Roshanak Sharafieh, Yen Lemire, James O'Rourke
To determine the origin of peripheral blood mononulclear cells (PBMC) that activate regulatory T cells in anterior chamber-associated immune deviation (ACAID), fluorescein-labeled PBMC were intravenously injected into mice before the mice received an intracameral injection of antigen. Six-24 hr after intracameral injection, fluorescein-labeled PBMC increased in the iris. Twenty-four-48 hr labeled cells decreased in the iris and increased in the thymus and spleen. The entry of the labeled PBMC into the anterior chamber and subsequent production of PBMC that transfer ACAID required the expression of CCR2 by the PBMC and the production of the chemokine CCL2 by the recipient of the PBMC. The results suggest that the intracameral injection of antigen induces i) the infiltration of F4/80(+) PBMC into the AC, ii) where these PBMC are converted to a regulatory phenotype, and iii) recirculate to activate T cells that suppress cell-mediated immunity.
{"title":"The Induction of Circulating, ACAID-Inducing Monocytes Requires CCR2/CCL2-Dependent Migration of Circulating F4/80(+) Cells into the Anterior Chamber.","authors":"Robert E Cone, Subhasis Chattopadhyay, Roshan Pais, Sourojit Bhowmick, Roshanak Sharafieh, Yen Lemire, James O'Rourke","doi":"10.4137/OED.S6113","DOIUrl":"https://doi.org/10.4137/OED.S6113","url":null,"abstract":"<p><p>To determine the origin of peripheral blood mononulclear cells (PBMC) that activate regulatory T cells in anterior chamber-associated immune deviation (ACAID), fluorescein-labeled PBMC were intravenously injected into mice before the mice received an intracameral injection of antigen. Six-24 hr after intracameral injection, fluorescein-labeled PBMC increased in the iris. Twenty-four-48 hr labeled cells decreased in the iris and increased in the thymus and spleen. The entry of the labeled PBMC into the anterior chamber and subsequent production of PBMC that transfer ACAID required the expression of CCR2 by the PBMC and the production of the chemokine CCL2 by the recipient of the PBMC. The results suggest that the intracameral injection of antigen induces i) the infiltration of F4/80(+) PBMC into the AC, ii) where these PBMC are converted to a regulatory phenotype, and iii) recirculate to activate T cells that suppress cell-mediated immunity. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"57-68"},"PeriodicalIF":0.0,"publicationDate":"2010-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/OED.S6113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585754","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}
Katragadda Suresh, Zhu Xiadong, Talluri S Ravi, Ashim K Mitra
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 [(3)H] 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 (B(0,+)). 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.
{"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":"Katragadda Suresh, Zhu Xiadong, Talluri S Ravi, Ashim K Mitra","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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 [(3)H] 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 (B(0,+)). 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. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"43-56"},"PeriodicalIF":0.0,"publicationDate":"2010-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585874","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 S Mo, H Kaplan, N G F Cooper
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.
{"title":"Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice.","authors":"W Fan, X Li, W Wang, J S Mo, H Kaplan, N G F Cooper","doi":"10.4137/oed.s2854","DOIUrl":"https://doi.org/10.4137/oed.s2854","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"1 ","pages":"23-41"},"PeriodicalIF":0.0,"publicationDate":"2010-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28888543","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}
Pub Date : 2010-03-10Print Date: 2010-01-01DOI: 10.4137/oed.s3612
Latif Abdul, Razique Abdul, R R Sukul, Siddiqui Nazish
The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.
{"title":"Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.","authors":"Latif Abdul, Razique Abdul, R R Sukul, Siddiqui Nazish","doi":"10.4137/oed.s3612","DOIUrl":"https://doi.org/10.4137/oed.s3612","url":null,"abstract":"<p><p>The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities. </p>","PeriodicalId":74362,"journal":{"name":"Ophthalmology and eye diseases","volume":"2 ","pages":"17-22"},"PeriodicalIF":0.0,"publicationDate":"2010-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/oed.s3612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31585873","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}