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Article ; Online: Canine and Feline Models of Inherited Retinal Diseases.

Petersen-Jones, Simon M / Komáromy, András M

Cold Spring Harbor perspectives in medicine

2024 Volume 14, Issue 2

Abstract: Naturally occurring inherited retinal diseases (IRDs) in cats and dogs provide a rich source of potential models for human IRDs. In many cases, the phenotypes between the species with mutations of the homologous genes are very similar. Both cats and dogs ...

Abstract	Naturally occurring inherited retinal diseases (IRDs) in cats and dogs provide a rich source of potential models for human IRDs. In many cases, the phenotypes between the species with mutations of the homologous genes are very similar. Both cats and dogs have a high-acuity retinal region, the area centralis, an equivalent to the human macula, with tightly packed photoreceptors and higher cone density. This and the similarity in globe size to that of humans means these large animal models provide information not obtainable from rodent models. The established cat and dog models include those for Leber congenital amaurosis, retinitis pigmentosa (including recessive, dominant, and X-linked forms), achromatopsia, Best disease, congenital stationary night blindness and other synaptic dysfunctions,
MeSH term(s)	Animals ; Dogs ; Cats ; Humans ; Cat Diseases/genetics ; Dog Diseases/genetics ; Retinal Diseases ; Eye Diseases, Hereditary/genetics ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/therapy ; Proteins ; Mutation
Chemical Substances	Proteins
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a041286
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Article: Manifestations of systemic disease in the retina and fundus of cats and dogs.

Beckwith-Cohen, Billie / Petersen-Jones, Simon M

Frontiers in veterinary science

2024 Volume 11, Page(s) 1337062

Abstract: The fundus is unique in that it is the only part of the body that allows for a noninvasive and uninterrupted view of vasculature and nervous tissue. Utilization of this can be a powerful tool in uncovering salient incidental findings which point to ... ...

Abstract	The fundus is unique in that it is the only part of the body that allows for a noninvasive and uninterrupted view of vasculature and nervous tissue. Utilization of this can be a powerful tool in uncovering salient incidental findings which point to underlying systemic diseases, and for monitoring response to therapy. Retinal venules and arterioles allow the clinician to assess changes in vascular color, diameter, outline, and tortuosity. The retina and optic nerve may exhibit changes associated with increased or decreased thickness, inflammatory infiltrates, hemorrhages, and detachments. While some retinal manifestations of systemic disease may be nonspecific, others are pathognomonic, and may be the presenting sign for a systemic illness. The examination of the fundus is an essential part of the comprehensive physical examination. Systemic diseases which may present with retinal abnormalities include a variety of disease classifications, as represented by the DAMNIT-V acronym, for Degenerative/Developmental, Anomalous, Metabolic, Neoplastic, Nutritional, Inflammatory (Infectious/Immune-mediated/ischemic), Toxic, Traumatic and Vascular. This review details systemic illnesses or syndromes that have been reported to manifest in the fundus of companion animals and discusses key aspects in differentiating their underlying cause. Normal variations in retinal anatomy and morphology are also considered.
Language	English
Publishing date	2024-02-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2024.1337062
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Article ; Online: Techniques for subretinal injections in animals.

Boyd, Ryan F / Petersen-Jones, Simon M

Veterinary ophthalmology

2024

Abstract: Subretinal injections are not commonly performed during clinical treatment of animals but are frequently used in laboratory animal models to assess therapeutic efficacy and safety of gene and cell therapy products. Veterinary ophthalmologists are often ... ...

Abstract	Subretinal injections are not commonly performed during clinical treatment of animals but are frequently used in laboratory animal models to assess therapeutic efficacy and safety of gene and cell therapy products. Veterinary ophthalmologists are often employed to perform the injections in the laboratory animal setting, due to knowledge of comparative ocular anatomy between species and familiarity with operating on non-human eyes. Understanding the different approaches used for subretinal injection in each species and potential complications that may be encountered is vital to achieving successful and reproducible results. This manuscript provides a summary of different approaches to subretinal injections in the most common animal model species, along with information from published literature and experience of the authors to educate novice or experienced surgeons tasked with performing these injections for the first time.
Language	English
Publishing date	2024-05-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2011043-1
ISSN	1463-5224 ; 1463-5216
ISSN (online)	1463-5224
ISSN	1463-5216
DOI	10.1111/vop.13219
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Article ; Online: CNG channel-related retinitis pigmentosa.

Gerhardt, Maximilian J / Petersen-Jones, Simon M / Michalakis, Stylianos

Vision research

2023 Volume 208, Page(s) 108232

Abstract: The genes CNGA1 and CNGB1 encode the alpha and beta subunits of the rod CNG channel, a ligand-gated cation channel whose activity is controlled by cyclic guanosine monophosphate (cGMP). Autosomal inherited mutations in either of the genes lead to a ... ...

Abstract	The genes CNGA1 and CNGB1 encode the alpha and beta subunits of the rod CNG channel, a ligand-gated cation channel whose activity is controlled by cyclic guanosine monophosphate (cGMP). Autosomal inherited mutations in either of the genes lead to a progressive rod-cone retinopathy known as retinitis pigmentosa (RP). The rod CNG channel is expressed in the plasma membrane of the outer segment and functions as a molecular switch that converts light-mediated changes in cGMP into a voltage and Ca
MeSH term(s)	Humans ; Cyclic Nucleotide-Gated Cation Channels/genetics ; Cyclic Nucleotide-Gated Cation Channels/metabolism ; Retinitis Pigmentosa/genetics ; Photoreceptor Cells, Vertebrate
Chemical Substances	Cyclic Nucleotide-Gated Cation Channels ; CNGB1 protein, human
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	200427-6
ISSN	1878-5646 ; 0042-6989
ISSN (online)	1878-5646
ISSN	0042-6989
DOI	10.1016/j.visres.2023.108232
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Article ; Online: Consensus guidelines for nomenclature of companion animal inherited retinal disorders.

Mowat, Freya M / Iwabe, Simone / Aguirre, Gustavo D / Petersen-Jones, Simon M

Veterinary ophthalmology

2024

Abstract: Companion animals, namely dogs, cats, and horses, can be affected with many forms of hereditary retinal disease. The number of such diseases characterized in the last decade has increased substantially, and nomenclature is nonstandardized, heterogenous, ... ...

Abstract	Companion animals, namely dogs, cats, and horses, can be affected with many forms of hereditary retinal disease. The number of such diseases characterized in the last decade has increased substantially, and nomenclature is nonstandardized, heterogenous, and confusing. We provide in this viewpoint article consensus guidelines for naming of companion animal hereditary retinal diseases, either prospectively or retrospectively. These consensus guidelines have been developed with the purpose of standardizing nomenclature. We provide examples for the iterative nomenclature process and a comprehensive File S1 on proposed renaming of previously described diseases.
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2011043-1
ISSN	1463-5224 ; 1463-5216
ISSN (online)	1463-5224
ISSN	1463-5216
DOI	10.1111/vop.13185
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Article ; Online: Large Animal Models of Retinitis Pigmentosa in Therapy Development and Preclinical Testing.

Occelli, Laurence M / Petersen-Jones, Simon M

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2560, Page(s) 233–248

Abstract: Large animal models are valuable for developing and testing translational therapies for inherited retinal dystrophies such as retinitis pigmentosa (RP). Gene augmentation therapy has been developed utilizing such models. Adeno-associated viral (AAV) ... ...

Abstract	Large animal models are valuable for developing and testing translational therapies for inherited retinal dystrophies such as retinitis pigmentosa (RP). Gene augmentation therapy has been developed utilizing such models. Adeno-associated viral (AAV) vectors have been frequently utilized and delivered by intravitreal or subretinal injection. In vivo longitudinal assessments of therapeutic outcomes are essential. These include regular ophthalmic examinations as well as detailed fundus assessments including confocal scanning laser ophthalmoscopy (cSLO) and high-resolution cross-sectional imaging of the retina by spectral domain-optical coherence tomography (SD-OCT). Retinal function assessment includes vision testing and electroretinography (ERG).
MeSH term(s)	Animals ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/therapy ; Models, Animal
Language	English
Publishing date	2022-11-08
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2651-1_22
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Article ; Online: Characterization of scotopic and mesopic rod signaling pathways in dogs using the On-Off electroretinogram.

Pasmanter, Nate / Petersen-Jones, Simon M

BMC veterinary research

2022 Volume 18, Issue 1, Page(s) 422

Abstract: Background: The On-Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors ...

Abstract	Background: The On-Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors and postreceptoral cells, including ON and OFF bipolar cells. Interspecies differences have been shown, with predominantly positive Off-response in humans and other primates and a negative Off-response in rodents and dogs. However, the rod signaling pathways that contribute to these differential responses have not been characterized. In this study, we designed a long flash protocol in the dog that varied in background luminance and stimulus strength allowing for some rod components to be present to better characterize how rod pathways vary from scotopic to mesopic conditions. Results: With low background light the rod a-wave remains while the b-wave is significantly reduced resulting in a predominantly negative waveform in mesopic conditions. Through modeling and subtraction of the rod-driven response, we show that rod bipolar cells saturate with dimmer backgrounds than rod photoreceptors, resulting in rod hyperpolarization contributing to a large underlying negativity with mesopic backgrounds. Conclusions: Reduction in rod bipolar cell responses in mesopic conditions prior to suppression of rod photoreceptor responses may reflect the changes in signaling pathway of rod-driven responses needed to extend the range of lighting conditions over which the retina functions.
MeSH term(s)	Humans ; Dogs ; Animals ; Signal Transduction ; Retina
Language	English
Publishing date	2022-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2191675-5
ISSN	1746-6148 ; 1746-6148
ISSN (online)	1746-6148
ISSN	1746-6148
DOI	10.1186/s12917-022-03505-z
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Article ; Online: Characterization of scotopic and mesopic rod signaling pathways in dogs using the On–Off electroretinogram

Pasmanter, Nate / Petersen-Jones, Simon M.

BMC Vet Res. 2022 Dec., v. 18, no. 1 p.422-422

2022

Abstract: BACKGROUND: The On–Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors ... ...

Abstract	BACKGROUND: The On–Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors and postreceptoral cells, including ON and OFF bipolar cells. Interspecies differences have been shown, with predominantly positive Off-response in humans and other primates and a negative Off-response in rodents and dogs. However, the rod signaling pathways that contribute to these differential responses have not been characterized. In this study, we designed a long flash protocol in the dog that varied in background luminance and stimulus strength allowing for some rod components to be present to better characterize how rod pathways vary from scotopic to mesopic conditions. RESULTS: With low background light the rod a-wave remains while the b-wave is significantly reduced resulting in a predominantly negative waveform in mesopic conditions. Through modeling and subtraction of the rod-driven response, we show that rod bipolar cells saturate with dimmer backgrounds than rod photoreceptors, resulting in rod hyperpolarization contributing to a large underlying negativity with mesopic backgrounds. CONCLUSIONS: Reduction in rod bipolar cell responses in mesopic conditions prior to suppression of rod photoreceptor responses may reflect the changes in signaling pathway of rod-driven responses needed to extend the range of lighting conditions over which the retina functions.
Keywords	dark adaptation ; dogs ; electroretinography ; photoreceptors ; retina
Language	English
Dates of publication	2022-12
Size	p. 422.
Publishing place	BioMed Central
Document type	Article ; Online
ZDB-ID	2191675-5
ISSN	1746-6148
ISSN	1746-6148
DOI	10.1186/s12917-022-03505-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Alternative splicing in CEP290 mutant cats results in a milder phenotype than LCACEP290 patients

Minella, Andrea L. / Narfström Wiechel, Kristina / Petersen‐Jones, Simon M.

Veterinary Ophthalmology. 2023 Jan., v. 26, no. 1 p.4-11

2023

Abstract: PURPOSE: The rdAc cat has an intronic mutation in the centrosomal 290 kDa (CEP290) gene resulting in a frameshift and a premature stop codon (c.6960 + 9 T > G, p.Ile2321AlafsTer3) predicted to truncate the protein by 157 amino acids. CEP290 mutations in ... ...

Abstract	PURPOSE: The rdAc cat has an intronic mutation in the centrosomal 290 kDa (CEP290) gene resulting in a frameshift and a premature stop codon (c.6960 + 9 T > G, p.Ile2321AlafsTer3) predicted to truncate the protein by 157 amino acids. CEP290 mutations in human patients cause a range or phenotypes including syndromic conditions and severe childhood loss of vision while the rdAc cat has a milder phenotype. We sought to further characterize the effect of rdAc mutation on CEP290 expression. METHODS: TaqMan quantitative real‐time polymerase chain reaction assays were used to compare wildtype and truncated transcript levels. Relative protein abundance was analyzed by Western blot. Immunohistochemistry (IHC) was performed to detect CEP290 protein. RESULTS: CEP290 mutant cats show low‐level (17.4% of wildtype cats) use of the wildtype splice site and usage of the mutant splice site. Western analysis shows retina from cats homozygous for the mutation has CEP290 protein that likely comprises a combination of both wildtype and truncated protein. IHC detects CEP290 in affected and control retina labeling the region of the interconnecting cilium. CONCLUSIONS: The comparably milder phenotype of CEP290 mutant cats is likely due to the retained production of some full‐length CEP290 protein with possible functional contributions from presence of truncated protein.
Keywords	Western blotting ; childhood ; homozygosity ; humans ; immunohistochemistry ; mutants ; mutation ; ophthalmology ; phenotype ; quantitative polymerase chain reaction ; retina ; stop codon ; vision
Language	English
Dates of publication	2023-01
Size	p. 4-11.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2011043-1
ISSN	1463-5224 ; 1463-5216
ISSN (online)	1463-5224
ISSN	1463-5216
DOI	10.1111/vop.13052
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Article ; Online: Alternative splicing in CEP290 mutant cats results in a milder phenotype than LCA

Minella, Andrea L / Narfström Wiechel, Kristina / Petersen-Jones, Simon M

Veterinary ophthalmology

2022 Volume 26, Issue 1, Page(s) 4–11

Abstract: Purpose: The rdAc cat has an intronic mutation in the centrosomal 290 kDa (CEP290) gene resulting in a frameshift and a premature stop codon (c.6960 + 9 T > G, p.Ile2321AlafsTer3) predicted to truncate the protein by 157 amino acids. CEP290 mutations in ...

Abstract	Purpose: The rdAc cat has an intronic mutation in the centrosomal 290 kDa (CEP290) gene resulting in a frameshift and a premature stop codon (c.6960 + 9 T > G, p.Ile2321AlafsTer3) predicted to truncate the protein by 157 amino acids. CEP290 mutations in human patients cause a range or phenotypes including syndromic conditions and severe childhood loss of vision while the rdAc cat has a milder phenotype. We sought to further characterize the effect of rdAc mutation on CEP290 expression. Methods: TaqMan quantitative real-time polymerase chain reaction assays were used to compare wildtype and truncated transcript levels. Relative protein abundance was analyzed by Western blot. Immunohistochemistry (IHC) was performed to detect CEP290 protein. Results: CEP290 mutant cats show low-level (17.4% of wildtype cats) use of the wildtype splice site and usage of the mutant splice site. Western analysis shows retina from cats homozygous for the mutation has CEP290 protein that likely comprises a combination of both wildtype and truncated protein. IHC detects CEP290 in affected and control retina labeling the region of the interconnecting cilium. Conclusions: The comparably milder phenotype of CEP290 mutant cats is likely due to the retained production of some full-length CEP290 protein with possible functional contributions from presence of truncated protein.
MeSH term(s)	Humans ; Animals ; Alternative Splicing ; Neoplasm Proteins ; Antigens, Neoplasm/genetics ; Cytoskeletal Proteins/genetics ; Mutation ; Phenotype ; Cell Cycle Proteins/genetics
Chemical Substances	Neoplasm Proteins ; Antigens, Neoplasm ; Cytoskeletal Proteins ; Cep290 protein, human ; Cell Cycle Proteins
Language	English
Publishing date	2022-12-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2011043-1
ISSN	1463-5224 ; 1463-5216
ISSN (online)	1463-5224
ISSN	1463-5216
DOI	10.1111/vop.13052
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