L’ophtalmologie vétérinaire : passé, présent et futur

This presentation on comparative and veterinary ophthalmology is divided into three sections: (1) ophthalmology in its infancy up until 1900, and founding period from 1901 to 1960; (2) ophthalmology as we know it today evolved from 1961 to 1980, and became a premier specialty in veterinary medicine (1981- now); and (3) the future in ophthalmology. Technology has had a profound effect on the development of ophthalmology with the discovery of the microscope and later on of the ophthalmoscope. Most of the early developments in veterinary ophthalmology occurred in Europe where schools of veterinary medicine had been established for decades. America was slow to recognize the specialty of veterinary ophthalmology, due to a lack of resources, time, and faculty devoted to clinics in the veterinary schools, and to additional constraints in small animal medicine and surgery. Veterinary ophthalmic pathology developed simultaneously and played a key role in clinical advances, resulting in the publication of significant textbooks on veterinary ophthalmology. Between 1960 and now, the majority of veterinary ophthalmologists have continued to contribute actively to this discipline. Significant advances during this period include: (1) the creation of veterinary ophthalmology societies or associations; 2) the creation of certifying veterinary ophthalmology boards (colleges); 3) the introduction of veterinary ophthalmology programs in academia; 4) the creation of clinical residencies for board certification; 5) the rapid emergence of private referral practices in ophthalmology; and 6) the advancement of veterinary ophthalmology research worldwide. With half a century of experience and significant progress, veterinary ophthalmology is facing a bright future with opportunities, along with potential difficulties. Our academic programs seem to have stalled in size while the number of private veterinary ophthalmology practices has exploded. Our capacities in clinical diagnosis and management of animal patients were greatly helped by the introduction of non-invasive imaging of the outer and deeper eye, as well as by the continuous development of new drugs. Human and veterinary ophthalmology are expected to benefit from further advances in both medical and surgical treatments. However, we need more research in breed-specific eye diseases, especially in dogs which appear second to man in the number of inherited eye diseases.Cet article sur l'ophtalmologie comparative et vétérinaire est divisé en trois périodes. (1) Avant 1900, avec les prémices de l'ophtalmologie, et de 1901 à 1960 quand ont été développées les bases fondatrices; (2) l'ophtalmologie a acquis sa forme actuelle de 1961 à 1980 et est devenue une spécialité phare en médecine vétérinaire dès 1981 ; et (3) l'avenir de l'ophtalmologie. Les progrès en médecine humaine et vétérinaire dépendent au moins en partie de l'évolution de la société et de l'économie, associée aux progrès technologiques. Les progrès technologiques ont contribué de façon importante au développement de l'ophtalmologie, avec l'invention du microscope et ensuite de l'ophtalmoscope (Hermann von Helmholtz, 1850). Les premières avancées en ophtalmologie vétérinaire ont eu lieu en Europe où les écoles de médecine vétérinaire existaient déjà depuis des décennies. En France, Eugène Nicolas, vétérinaire de l'armée, a ecrit trois livres sur l'ophtalmologie vétérinaire et comparative en 1898, 1914 et 1928. En Allemagne, l'ophtalmologie vétérinaire a pris son essor entre 1875 et 1910, à partir des écoles vétérinaires de Berlin, Stuttgart, Munich, et Vienne. Rudolf Berlin (1833-1897), ophtalmologue humain, a co-édité avec Oscar Eversbush (Munich) la première revue sur l'ophtalmologie vétérinaire (Zeitschrift für vergleichende Augenheilkunde) publiée de 1882 à 1893. Après avoir terminé ses études de médecine, Josef Bayer (1847-1925) est devenu vétérinaire en 1874 et ensuite professeur à la Faculté Vétérinaire de Vienne. Bayer est surtout connu pour son ouvrage pionnier et exhaustif sur l'ophtalmologie vétérinaire, Augenheilkunde, publié en 1900, et réédité en 1906, 1910, et 1914. Aux Pays-Bas, Jakob est surtout connu pour ses deux livres, Tierärztliche Augenheilkunde (1920) et Pathologische Anatomie des Auges der Tiere (1927). Henry Gray (1865-1939), un des premiers praticiens de petits animaux à Londres (1887), a traduit en anglais la deuxième édition du livre de Nicolas Ophtalmologie Vétérinaire et Comparée, le premier ouvrage sur l'ophtalmologie du début du XXesiècle ! Les États-Unis ont tardé à reconnaître l'ophtalmologie en tant que spécialité vétérinaire, à cause d'un manque de ressources, de temps et d'enseignants alloués aux cliniques dans les écoles vétérinaires, et des contraintes supplémentaires existant en médecine et en chirurgie des petits animaux. W. N. Sharp, médecin au Indiana Veterinary College et Indianapolis City Hospital, a écrit un petit livre intitulé Ophthalmology for Veterinarians. L'anatomie pathologique en ophtalmologie vétérinaire s'est développée en même temps et a fourni des bases essentielles au développement de l'ophtalmologie vétérinaire clinique. Parmi les ouvrages significatifs, on note Pathologische Anatomie des Auges der Tier (Jakob 1927), et Lehrbuch der Pathologischen Anatomie der Haustiere (Kitt 1901, deuxième édition). De 1960 à nos jours, la majorité des ophtalmologues vétérinaires ont continué de contribuer activement à cette discipline. Des progrès significatifs ont été accomplis durant cette période, tels que 1) la création de sociétés ou associations d'ophtalmologie vétérinaire ; 2) la création de certificats de spécialité en ophtalmologie vétérinaire; 3) l'instauration de programmes d'ophtalmologie vétérinaire dans les études; 4) la création de postes d'interne des cliniques pour l'obtention d'un diplôme en ophtalmologie

Influence of age on ocular biomechanical properties in a canine glaucoma model with ADAMTS10 mutation

<div><p>Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with <i>ADAMTS10</i> mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from <i>ADAMTS10-</i>mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs.</p></div

Photoperiodic regime influences onset of lens opacities in a non-human primate

Background Opacities of the lens are typical age-related phenomena which have a high influence on photoreception and consequently circadian rhythm. In mouse lemurs, a small bodied non-human primate, a high incidence (more than 50% when >seven years) of cataracts has been previously described during aging. Previous studies showed that photoperiodically induced accelerated annual rhythms alter some of mouse lemurs’ life history traits. Whether a modification of photoperiod also affects the onset of age dependent lens opacities has not been investigated so far. The aim of this study was therefore to characterise the type of opacity and the mouse lemurs’ age at its onset in two colonies with different photoperiodic regimen. Methods Two of the largest mouse lemur colonies in Europe were investigated: Colony 1 having a natural annual photoperiodic regime and Colony 2 with an induced accelerated annual cycle. A slit-lamp was used to determine opacities in the lens. Furthermore, a subset of all animals which showed no opacities in the lens nucleus in the first examination but developed first changes in the following examination were further examined to estimate the age at onset of opacities. In total, 387 animals were examined and 57 represented the subset for age at onset estimation. Results The first and most commonly observable opacity in the lens was nuclear sclerosis. Mouse lemurs from Colony 1 showed a delayed onset of nuclear sclerosis compared to mouse lemurs from Colony 2 (4.35 ± 1.50 years vs. 2.75 ± 0.99 years). For colony 1, the chronological age was equivalent to the number of seasonal cycles experienced by the mouse lemurs. For colony 2, in which seasonal cycles were accelerated by a factor of 1.5, mouse lemurs had experienced 4.13 ± 1.50 seasonal cycles in 2.75 ± 0.99 chronological years. Discussion Our study showed clear differences in age at the onset of nuclear sclerosis formation between lemurs kept under different photoperiodic regimes. Instead of measuring the chronological age, the number of seasonal cycles (N = four) experienced by a mouse lemur can be used to estimate the risk of beginning nuclear sclerosis formation. Ophthalmological examinations should be taken into account when animals older than 5–6 seasonal cycles are used for experiments in which unrestricted visual ability has to be ensured. This study is the first to assess and demonstrate the influence of annual photoperiod regime on the incidence of lens opacities in a non-human primate

Mapping of the Disease Locus and Identification of ADAMTS10 As a Candidate Gene in a Canine Model of Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies

Isolation and characterization of the crystallins of the normal and cataractous canine lens.

The lens crystallins were analyzed in normal dogs and Miniature Schnauzer dogs with congenital cataract formation. There was an increase in the relative proportions of α and β L -crystallin and a decrease in βH and γ -crystallin with increasing age in the noncataractous lens. These trends were advanced in the age-matched cataractous lenses. “Advanced aging” trends were also noted in various polypeptide components of β-crystallin. Specifically, the appearance of a 29K band as well as a reversal of the 26K to 27.6K ratio occurred at an earlier age in the cataractous lens than in the clear lens. Three subunits of approximately 19K, 20K, and 21.5K were present on SDS-PAGE for α-crystallin from the cataractous lens as opposed to only two of 19K and 21.5K from the clear lens. However, if the protein was not heated following resolubilization in buffer containing 2% SDS and 5% 2-mercaptoethanol, only two subunits of 20K and 21.5K were evident in both clear and cataractous lenses. The electrophoretic behavior observed for both α and γ-crystallins did not appear to be age related

Isolation and characterization of the crystallins of the normal and cataractous canine lens.

The lens crystallins were analyzed in normal dogs and Miniature Schnauzer dogs with congenital cataract formation. There was an increase in the relative proportions of α and β L -crystallin and a decrease in βH and γ -crystallin with increasing age in the noncataractous lens. These trends were advanced in the age-matched cataractous lenses. “Advanced aging” trends were also noted in various polypeptide components of β-crystallin. Specifically, the appearance of a 29K band as well as a reversal of the 26K to 27.6K ratio occurred at an earlier age in the cataractous lens than in the clear lens. Three subunits of approximately 19K, 20K, and 21.5K were present on SDS-PAGE for α-crystallin from the cataractous lens as opposed to only two of 19K and 21.5K from the clear lens. However, if the protein was not heated following resolubilization in buffer containing 2% SDS and 5% 2-mercaptoethanol, only two subunits of 20K and 21.5K were evident in both clear and cataractous lenses. The electrophoretic behavior observed for both α and γ-crystallins did not appear to be age related

Reduced, oxidized, and protein-bound glutathione concentrations in normal and cataractous lenses in the dog.

Amounts of reduced, oxidized, and protein-bound glutathione (GSH) were measured in normal and cataractous lenses of pups and adult dogs. Lenses from pups included normal lenses from clinically normal pups, clear lenses from Beagle pups bred for glaucoma, and congenital cataractous lenses from Miniature Schnauzer pups. Lenses from adults included normal lenses from normal mixed-breed dogs, congenital cataractous lenses from Miniature Schnauzers, and complete mature cataractous lenses from clinical patients of different breeds. Glutathione in the normal lenses from pups and adult dogs is predominantly reduced GSH; oxidized GSH is about 2.1% to 2.6% of the reduced GSH values. The reduced GSH values are lower in normal pups [7.08 mumoles/g (wet wt) of lens] than in adults [7.83 mumoles/g (wet wt) of lens]; reduced GSH values decrease further in cataract formation. The decrease in oxidized GSH values parallel those of reduced GSH, except in the advanced cataracts of clinical patients in which oxidized GSH [0.045 mumoles/g (wet wt) of lens] was 9% of the GSH values. The GSH bound to soluble and insoluble lens proteins of congenital cataractous Miniature Schnauzer pups was significantly (P less than 0.01 and P less than 0.02, respectively) lower per gram of protein than that in pups with normal lenses. However, the soluble and insoluble protein-bound GSH of congenital cataractous lenses of adult Miniature Schnauzers and lenses in clinical patients with mature cataracts [based on mumole of GSH/g (wet wt) of lens] were not significantly different (P greater than 0.05) from that in adult dogs with normal lenses

Reduced, oxidized, and protein-bound glutathione concentrations in normal and cataractous lenses in the dog.

Amounts of reduced, oxidized, and protein-bound glutathione (GSH) were measured in normal and cataractous lenses of pups and adult dogs. Lenses from pups included normal lenses from clinically normal pups, clear lenses from Beagle pups bred for glaucoma, and congenital cataractous lenses from Miniature Schnauzer pups. Lenses from adults included normal lenses from normal mixed-breed dogs, congenital cataractous lenses from Miniature Schnauzers, and complete mature cataractous lenses from clinical patients of different breeds. Glutathione in the normal lenses from pups and adult dogs is predominantly reduced GSH; oxidized GSH is about 2.1% to 2.6% of the reduced GSH values. The reduced GSH values are lower in normal pups [7.08 mumoles/g (wet wt) of lens] than in adults [7.83 mumoles/g (wet wt) of lens]; reduced GSH values decrease further in cataract formation. The decrease in oxidized GSH values parallel those of reduced GSH, except in the advanced cataracts of clinical patients in which oxidized GSH [0.045 mumoles/g (wet wt) of lens] was 9% of the GSH values. The GSH bound to soluble and insoluble lens proteins of congenital cataractous Miniature Schnauzer pups was significantly (P less than 0.01 and P less than 0.02, respectively) lower per gram of protein than that in pups with normal lenses. However, the soluble and insoluble protein-bound GSH of congenital cataractous lenses of adult Miniature Schnauzers and lenses in clinical patients with mature cataracts [based on mumole of GSH/g (wet wt) of lens] were not significantly different (P greater than 0.05) from that in adult dogs with normal lenses