Medicine and Health Sciences Commons^™

Consequences And Management Of Canine Brachycephaly In Veterinary Practice: Perspectives From Australian Veterinarians And Veterinary Specialists, Anne Fawcett, Vanessa Barrs, Magdoline Awad, Georgina Child, Laurencie Brunel, Erin Mooney, Fernando Martinez-Taboada, Beth Mcdonald, Paul Mcgreevy

Paul McGreevy, PhD

This article, written by veterinarians whose caseloads include brachycephalic dogs, argues that there is now widespread evidence documenting a link between extreme brachycephalic phenotypes and chronic disease, which compromises canine welfare. This paper is divided into nine sections exploring the breadth of the impact of brachycephaly on the incidence of disease, as indicated by pet insurance claims data from an Australian pet insurance provider, the stabilization of respiratory distress associated with brachycephalic obstructive airway syndrome (BOAS), challenges associated with sedation and the anaesthesia of patients with BOAS; effects of brachycephaly on the brain and associated neurological conditions, dermatological conditions associated …

Window Into Retinal Studies, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa.

Safety In Nonhuman Primates Of Ocular Aav2-Rpe65, A Candidate Treatment For Blindness In Leber Congenital Amaurosis, Samuel G. Jacobson, Sanford L. Boye, Tomas S. Aleman, Thomas J. Conlon, Caroline J. Zeiss, Alejandro J. Roman, Artur V. Cideciyan, Sharon B. Schwartz, András M. Komáromy, Michelle Doobrajh, Andy Y. Cheung, Alexandar Sumaroka, Susan E. Pearce-Kelling, Gustavo D. Aguirre, Shalesh Kaushal, Albert M. Maguire, Terence R. Flotte, William W. Hauswirth

Gustavo D. Aguirre, VMD, PhD

Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV- RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2. RPE65 in RPE65 -mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vector-related toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular …

Photoreceptor Cell Death, Proliferation And Formation Of Hybrid Rod/S-Cone Photoreceptors In The Degenerating Stk38l Mutant Retina, Ágnes I. Berta, Kathleen Boesze-Battaglia, Sem Genini, Orly Goldstein, Paul J. O'Brien, Ágoston Szél, Gregory M. Acland, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell …

Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair R. Philip, Sarah J. P Lindauer, Susan E. Pearce-Kelling, Roberts F. Mullins, Alexander S. Graphodatsky, Daniel Ripoll, Jeanette S. Felix, Edwin M. Stone, Gregory M. Acland, Gustavo D. 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 and …

Long-Term Restoration Of Rod And Cone Vision By Single Dose Raav-Mediated Gene Transfer To The Retina In A Canine Model Of Childhood Blindness, Gregory M. Acland, Gustavo D. Aguirre, Jean Bennett, Tomas S. Aleman, Artur V. Cideciyan, Jeannette Bennicelli, Nadine S. Dejneka, Susan E. Pearce-Kelling, Albert M. Maguire, Krzysztof Palczewski, William W. Hauswirth, Samuel G. Jacobson

Gustavo D. Aguirre, VMD, PhD

The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no …

Free-Roaming Dogs In Developing Countries: The Benefits Of Capture, Neuter, And Return Programs, Jennifer Jackman, Andrew N. Rowan

Jennifer Jackman, Ph.D.

This chapter provides an overview of animal welfare and public health problems associated with free-roaming dog populations and strategies to resolve these problems. Placing CNR programs in the context of earlier dog and rabies control methods, the chapter explores CNR’s potential to overcome some of the shortcomings of earlier approaches and to improve animal welfare, reduce dog population growth, and prevent the spread of rabies and other canine-transmitted diseases. Constraints and current debates on current implementation of CNR programs are also examined.

Metabolic Labeling Of Rod Outer Segment Phospholipids In Miniature Poodles With Progressive Rod-Cone Degeneration (Prcd), Mary Wetzel, Christian Fahlman, Paul O'Brien, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD