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Development Of A Surgical Instrument Prototype To Perform A More Precise Capsulorhexis, Kirk Haugen 2016 Southern Adventist Univeristy

Development Of A Surgical Instrument Prototype To Perform A More Precise Capsulorhexis, Kirk Haugen

Journal of Interdisciplinary Undergraduate Research

Performing capsulorhexis is often considered the most difficult part of cataract surgery. Not only is it difficult, but performing it correctly is important for refractive outcomes.4 Inaccurate capsulorhexes are associated with complications including posterior capsular opacification, capsular fibrosis, and capsular phimosis.6 This study investigates the possibility of a proposed surgical instrument producing more precise capsulorhexes as determined by the circularity index. 60 capsulorhexes were performed on cigarette paper laid over clay - half using the continuous curvilinear capsulorhexis (CCC) method, and half using the proposed instrument. The precision of the capsulorhexis was then measured using the circularity index. The ...


Ophthalmic Drugs 2016, Lorne Yudcovitch 2016 Pacific University

Ophthalmic Drugs 2016, Lorne Yudcovitch

Faculty Scholarship (COO)

This chart serves as a basic reference guide showcasing the most common ophthalmic drugs, updated as of the beginning of 2016. Both topical ophthalmic and oral medications indicated for the eye are included, with Food and Drug Administration/American Academy of Ophthalmology cap color representation when indicated. Medications with generic versions are noted with an asterisk(*).


Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland 2016 University of Pennsylvania

Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland

Gustavo D. Aguirre, VMD, PhD

Fine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal or ...


Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human ...


Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre 2016 University of Pennsylvania

Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and ...


Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András Komáromy, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András Komáromy, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

A standard operating microscope was modified with a bandpass infrared filter in the light path and infrared image intensifiers for each of the 2 eyepieces. We evaluated this system for subretinal injections in normal control dogs and those with a mutation in the rhodopsin gene. Rhodopsin-mutant dogs are a model for human autosomal dominant retinitis pigmentosa, and their retinas degenerate faster when exposed to modest light levels as used in routine clinical examinations. We showed that the mutant retinas developed severe generalized degeneration when exposed to the standard operating microscope light but not the infrared light. The modified operating microscope ...


Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected ...


Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. AP-1 has been proposed as a key intermediate linking exposure to light and photoreceptor cell death in rodent light-damage models. Inhibition of AP-1 associated with steroid administration also prevents light damage. In this study the role of steroids in inhibiting AP-1 activation and/or in preventing photoreceptor degeneration was examined in the rhodopsin mutant dog model. METHODS. The dogs were dark adapted overnight, eyes dilated with mydriatics; the right eye was light occluded and the fundus of the left eye photographed (∼15–17 overlapping frames) with a fundus camera. For biochemical studies, the dogs remained in the dark for ...


Canine Rd3 Mutation Establishes Rod-Cone Dysplasia Type 2 (Rcd2) As Ortholog Of Human And Murine Rd3, Anna Kukekova, Orly Goldstein, Jennifer Johnson, Malcolm Richardson, Susan Pearce-Kelling, Anand Swaroop, James Friedman, Gustavo Aguirre, Gregory Acland 2016 University of Pennsylvania

Canine Rd3 Mutation Establishes Rod-Cone Dysplasia Type 2 (Rcd2) As Ortholog Of Human And Murine Rd3, Anna Kukekova, Orly Goldstein, Jennifer Johnson, Malcolm Richardson, Susan Pearce-Kelling, Anand Swaroop, James Friedman, Gustavo Aguirre, Gregory Acland

Gustavo D. Aguirre, VMD, PhD

Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend ...


Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-ichiro Komatsu, Gustavo Aguirre 2016 University of Pennsylvania

Blinded By The Light: Retinal Phototoxicity In The Context Of Safety Studies, Maria Cristina De Vera Mudry, Sven Kronenberg, Shun-Ichiro Komatsu, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

No abstract provided.


Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina Guziewicz, Barbara Zangerl, Sarah Lindauer, Robert Mullins, Lynne Sandmeyer, Bruce Grahn, Edwin Stone, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina Guziewicz, Barbara Zangerl, Sarah Lindauer, Robert Mullins, Lynne Sandmeyer, Bruce Grahn, Edwin Stone, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting ...


A Naturally Occurring Mutation Of The Opsin Gene (T4r) In Dogs Affects Glycosylation And Stability Of The G Protein-Coupled Receptor, Li Zhu, Geeng-Fu Jang, Beata Jastrzebska, Slawomir Filipek, Susan Pearce-Kelling, Gustavo Aguirre, Ronald Stenkamp, Gregory Acland, Krzysztof Palczewski 2016 University of Pennsylvania

A Naturally Occurring Mutation Of The Opsin Gene (T4r) In Dogs Affects Glycosylation And Stability Of The G Protein-Coupled Receptor, Li Zhu, Geeng-Fu Jang, Beata Jastrzebska, Slawomir Filipek, Susan Pearce-Kelling, Gustavo Aguirre, Ronald Stenkamp, Gregory Acland, Krzysztof Palczewski

Gustavo D. Aguirre, VMD, PhD

Rho (rhodopsin; opsin plus 11-cis-retinal) is a prototypical G protein-coupled receptor responsible for the capture of a photon in retinal photoreceptor cells. A large number of mutations in the opsin gene associated with autosomal dominant retinitis pigmentosa have been identified. The naturally occurring T4R opsin mutation in the English mastiff dog leads to a progressive retinal degeneration that closely resembles human retinitis pigmentosa caused by the T4K mutation in the opsin gene. Using genetic approaches and biochemical assays, we explored the properties of the T4R mutant protein. Employing immunoaffinity-purified Rho from affected RHOT4R/T4R dog retina, we found that the ...


Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. The T4R RHO mutant dog retina shows retinal degeneration with exposures to light comparable to those used in clinical eye examinations of patients. To define the molecular mechanisms of the degeneration, AP-1 DNA-binding activity, composition, posttranslational modification of the protein complex, and modulation of ERK/MAPK signaling pathways were examined in light-exposed mutant retinas.

METHODS. Dark-adapted retinas were exposed to short-duration light flashes from a retinal camera used clinically for retinal photography and were collected at different time points after exposure. Electrophoretic mobility shift assay (EMSA), supershift EMSA, Western blot analysis, and immunocytochemistry were used to examine AP-1 signaling ...


Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Age-Dependent Disease Expression Determines Remodeling Of The Retinal Mosaic In Carriers Of Rpgr Exon Orfn15 Mutations, William Beltran, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15. METHODS. Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events. RESULTS. A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these ...


Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre 2016 University of Pennsylvania

Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and ...


Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Steroids Do Not Prevent Photoreceptor Degeneration In The Light-Exposed T4r Rhodopsin Mutant Dog Retina Irrespective Of Ap-1 Inhibition, Danian Gu, William Beltran, Sue Pearce-Kelling, Zexiao Li, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. AP-1 has been proposed as a key intermediate linking exposure to light and photoreceptor cell death in rodent light-damage models. Inhibition of AP-1 associated with steroid administration also prevents light damage. In this study the role of steroids in inhibiting AP-1 activation and/or in preventing photoreceptor degeneration was examined in the rhodopsin mutant dog model. METHODS. The dogs were dark adapted overnight, eyes dilated with mydriatics; the right eye was light occluded and the fundus of the left eye photographed (∼15–17 overlapping frames) with a fundus camera. For biochemical studies, the dogs remained in the dark for ...


Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András Komáromy, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Operating In The Dark: A Night-Vision System For Surgery In Retinas Susceptible To Light Damage, András Komáromy, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

A standard operating microscope was modified with a bandpass infrared filter in the light path and infrared image intensifiers for each of the 2 eyepieces. We evaluated this system for subretinal injections in normal control dogs and those with a mutation in the rhodopsin gene. Rhodopsin-mutant dogs are a model for human autosomal dominant retinitis pigmentosa, and their retinas degenerate faster when exposed to modest light levels as used in routine clinical examinations. We showed that the mutant retinas developed severe generalized degeneration when exposed to the standard operating microscope light but not the infrared light. The modified operating microscope ...


Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected ...


Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland 2016 University of Pennsylvania

Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland

Gustavo D. Aguirre, VMD, PhD

Fine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal or ...


Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human ...


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