Trends in companion animal access to veterinary care in Canada, 2007 to 2020.

Objective: Assess trends in access to veterinary care for companion animals in Canada. Procedure: Analysis and integration of available data, 2007 to 2020. Results: Cumulative growth in the Canadian veterinary workforce was 38%, and 49% for companion animal veterinarians. Clients per companion animal veterinarian decreased 30% from 2008 to 2020. Absolute client numbers increased 1.3%, compared to pet population growth of 17%. Medicalized pets (those that had received veterinary care in the past year) increased 25%, from 9.02 million in 2007 to 11.24 million in 2020. Non-medicalized pets increased 1.8%, from 4.48 million to 4.56 million. In 2007, 33% of pets were non-medicalized, compared to 29% (15% of dogs and 42% of cats) in 2020. There was a cumulative increase of 31% for total non-medicalized dogs, and a change of -5.6% for cats. Gross and net revenues per client increased by 99 and 112%, respectively, compared to cumulative inflation of 21%. Conclusion and clinical relevance: The analysis identified a large cohort of pets that had not received veterinary care each year. The trends were fewer clients per veterinarian, each paying higher veterinary costs, and suggested a relative, rather than absolute, veterinary capacity shortage overall. Accessible care-provision models must be encouraged, regulated for, and allowed to flourish alongside traditional models.

Tendances en matière d'accès des animaux de compagnie aux soins vétérinaires au Canada, 2007 à 2020. Objectif: Évaluer les tendances en matière d'accès aux soins vétérinaires pour les animaux de compagnie au Canada. Procédure: Analyse et intégration des données disponibles, 2007 à 2020. Résultats: La croissance cumulative de la main-d'œuvre vétérinaire canadienne était de 38 %, et de 49 % pour les médecins vétérinaires d'animaux de compagnie. Le nombre de clients par vétérinaire pour animaux de compagnie a diminué de 30 % entre 2008 et 2020. Le nombre absolu de clients a augmenté de 1,3 %, comparé à une croissance de la population d'animaux de compagnie de 17 %. Les animaux de compagnie médicalisés (ceux qui ont reçu des soins vétérinaires au cours de l'année écoulée) ont augmenté de 25 %, passant de 9,02 millions en 2007 à 11,24 millions en 2020. Les animaux de compagnie non médicalisés ont augmenté de 1,8 %, passant de 4,48 millions à 4,56 millions. En 2007, 33 % des animaux de compagnie étaient non médicalisés, contre 29 % (15 % des chiens et 42 % des chats) en 2020. Il y a eu une augmentation cumulée de 31 % pour le total des chiens non médicalisés, et une variation de ­5,6 % pour les chats. Les revenus bruts et nets par client ont augmenté respectivement de 99 et 112 %, par rapport à une inflation cumulée de 21 %. Conclusion et pertinence clinique: L'analyse a identifié chaque année une large cohorte d'animaux de compagnie qui n'avaient pas reçu de soins vétérinaires. Les tendances étaient moins de clients par vétérinaire, chacun payant des frais vétérinaires plus élevés, et suggéraient une pénurie globale de capacité vétérinaire relative plutôt qu'absolue. Les modèles de prestation de soins accessibles doivent être encouragés, réglementés et autorisés à prospérer aux côtés des modèles traditionnels.(Traduit par Dr Serge Messier).

OPA1 deficiency associated with increased autophagy in retinal ganglion cells in a murine model of dominant optic atrophy.

PURPOSE: To examine retinal ganglion cell (RGC) and axonal abnormalities in an ENU-induced mutant mouse carrying a protein-truncating nonsense mutation in OPA1. Mutations in the OPA1 gene cause autosomal dominant optic atrophy (ADOA) in which loss of RGCs followed by myelin degeneration in the optic nerve leads to progressive decrease in visual acuity. METHODS: Ultrastructure of the optic nerve was examined in heterozygous mutants and wild-type littermate controls at 6, 9, and 24 months using electron microscopy. The RGC layer was examined at 6 and 24 months. RESULTS: There was an increase in the number of autophagosomes in the RGC layer in heterozygous mutants compared with wild type at 24 months. Signs of optic nerve degeneration were seen as early as 9 months in Opa1(+/-) mice, with more severe degeneration by 24 months. By 24 months, degeneration of axons was also seen in control mice. Numbers of opaque mitochondria in the Opa1(+/-) mice increased at 6 and 24 months, possibly representing an increase in the density of cristae to fulfill the energy requirements of the axon. In addition, mitochondria with vesiculation of the inner membranes, similar to the mutant mitochondria described in a mouse model of Charcot-Marie-Tooth type 2A, were observed. CONCLUSIONS: Mutations in OPA1 cause pathologic changes to optic nerve axons that are similar to, but occur earlier than, age-related degeneration. Increased autophagy is likely to result from an increase in abnormal mitochondria and could be one mechanism contributing to RGC loss and subsequent optic atrophy seen in ADOA.

Increase in mitochondrial density within axons and supporting cells in response to demyelination in the Plp1 mouse model.

We used the Plp1-overexpressing transgenic mouse model to investigate whether progressive demyelination of axons results in adaptive changes involving mitochondria within the axons. These models have myelinated axons from birth but gradually lose myelin and develop axonal loss associated with progressive neurological disability analogous to patients with secondary progressive mulltiple sclerosis (SPMS). At 1 and 2 months, electron microscopy demonstrated a significant increase in intraaxonal mitochondrial density in the homozygous line 72 Plp1-overexpressing mice compared with wild type (1.43 +/- 0.31 vs. 0.84 +/- 0.16 microm(-3), P = 0.031; 1.66 +/- 0.11 vs. 0.92 +/- 0.43 microm(-3), P = 0.02) and a significant increase at 1 and 4 months in the density of mitochondria in the surrounding cells in the same mice (1.86 +/- 0.31 vs. 0.81 +/- 0.30 microm(-3), P = 0.006; 2.77 +/- 0.44 vs. 1.37 +/- 0.42 microm(-3), P = 0.016). At both 1 and 4 months, COX histochemistry and time-lapse histochemistry demonstrated a significant increase in mitochondrial activity and rate of mitochondrial activity in the homozygous Plp1-overexpressing mouse optic nerve compared with the wild type (112.37 +/- 11.9 vs. 136.89 +/- 9.1 MeanD, P = 0.006; 128.02 +/- 3.0 vs. 188.77 +/- 9.7 MeanD P < 0.001; Rate -0.78 +/- 0.25 vs. -0.58 +/- 0.15 MeanD min(-1), P < 0.001; -1.48 +/- 0.15 vs. 0.51 +/- 0.17 MeanD min(-1), P < 0.001, respectively). We propose that adaptive changes involving mitochondria occur within CNS axons in Plp1-overexpressing mice, which may be detrimental to long-term viability. Analogous changes occurring in chronically demyelinated axons in MS lesions would be one mechanism increasing axonal vulnerability in SPMS.

A missense mutation in the murine Opa3 gene models human Costeff syndrome.

Opa3 mRNA is expressed in all tissues examined to date, but currently the function of the OPA3 protein is unknown. Intriguingly, various mutations in the OPA3 gene lead to two similar diseases in humans: autosomal dominant inherited optic atrophy and cataract (ADOAC) and a metabolic condition; type 3-methylglutaconic aciduria (MGA). Early onset bilateral optic atrophy is a common characteristic of both disorders; retinal ganglion cells are lost and visual acuity is impaired from an early age. In order to investigate the function of the OPA3 protein, we have generated a novel ENU-induced mutant mouse carrying a missense mutation in the OPA3 gene. The heterozygous mutation in exon 2, causes an amino acid change p.L122P (c.365T>C), which is predicted to alter tertiary protein structure. In the heterozygous state, the mice appear uncompromised however; in the homozygous state mice display some of the features of MGA. Visual function is severely reduced, consistent with significant loss of retinal ganglion cells and degeneration of axons in the optic nerve. In the homozygous optic nerve, there was evidence of increased mitochondrial activity, as demonstrated by the increased presence of mitochondrial marker Cytochrome C Oxidase (COX) histochemistry. Mice homozygous for the opa3(L122P) mutation also display a severe multi-systemic disease characterized by reduced lifespan (majority dying before 4 months), decreased weight, dilated cardiomyopathy, extrapyramidal dysfunction and gross neuro-muscular defects. All of these defects are synonymous with the phenotypic characteristics of Type III MGA found in humans. This model will be of major importance for future studies of the specific function of the OPA3 gene.

Increased axonal mitochondrial activity as an adaptation to myelin deficiency in the Shiverer mouse.

Axonal pathology in multiple sclerosis (MS) has been described for over a century, but new insights into axonal loss and disability have refocused interest in this area. There is evidence of oxidative damage to mitochondrial DNA in chronic MS plaques, suggesting that mitochondrial failure may play a role in MS pathology. We propose that in the chronic absence of myelin the maintenance of conduction relies partially on an increase in mitochondria to provide energy. This increased energy requirement also promotes reactive oxygen species (ROS), because most intraaxonal ROS are generated by mitochondria. If antioxidant defenses are overwhelmed by an excess of ROS, this may result in damage to the axon. Our aim was to investigate whether a chronic lack of myelin results in adaptive changes involving mitochondria within the axon. We investigated this in the shiverer mouse. This myelin basic protein gene mutant provides a model of how adult central nervous system (CNS) axons cope with the chronic absence of a compact myelin sheath. Cytochrome c histochemistry demonstrated a twofold increase in mitochondrial activity in white matter tracts of shiverer, and electron microscopy confirmed a significantly higher number of mitochondria within the dysmyelinated axons. Our data demonstrate that there are adaptive changes involving mitochondria occurring within CNS axons in shiverer mice in response to a lack of myelin. This work contributes to our understanding of the adaptive changes occurring in response to a lack of myelin in a noninflammatory environment similar to the situation seen in chronically demyelinated MS plaques.