Age-related changes in morphology and secretory responses of male rat lacrimal gland

Draper, Clare E.; Adeghate, Ernest; Lawrence, Paul A.; Pallot, D. J.; Garner, A.; Singh, Jaipaul

doi:10.1016/s0165-1838(98)00026-5

Cited by 48 publications

(30 citation statements)

References 22 publications

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“…• C for 24 h. Ultrathin sections were made using a diamond knife (Agar Scientific, Stansted, UK) and treated with uranyl acetate and lead citrate as previously described (Draper et al 1998). The images were collected using a Phillips CM 2000 electron microscope.…”

Section: Electron Microscopymentioning

confidence: 99%

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Howarth¹,

Qureshi²,

Sobhy³

et al. 2011

Experimental Physiology

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Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease, the aim of the study was to investigate the effects of feeding type 2 diabetic Goto-Kakizaki (GK) rats either high-or low-fat diets on cardiomyocyte structure and function. The GK rats were fed either a high-fat diet (HFD) or a low-fat diet (LFD) from the age of 2 months for a period of 7 months. The GK-HFD rats gained more weight, ate less food and drank less water compared with GK-LFD rats. At 7 months, non-fasting blood glucose was higher in GK-LFD (334 ± 35 mg dl −1 ) compared with GK-HFD rats (235 ± 26 mg dl −1 ). Feeding GK rats with a HFD had no significant effect on glucose clearance following a glucose challenge. Time-to-peak (t peak ) shortening was reduced in myocytes from GK-HFD (131.8 ± 2.1 ms) compared with GK-LFD rats (144.5 ± 3.0 ms), and time-to-half (t 1 /2 ) relaxation of shortening was also reduced in myocytes from GK-HFD (71.7 ± 6.9 ms) compared with GK-LFD rats (86.1 ± 3.6 ms). The HFD had no significant effect on the amplitude of shortening. The HFD had no significant effect on t peak , t 1 /2 decay, amplitude of the Ca 2+ transient, myofilament sensitivity to Ca 2+ , sarcoplasmic reticulum Ca 2+ content, fractional release of Ca 2+ and the rate of Ca 2+ uptake. Structurally, ventricular myocytes from GK-HFD rats showed extensive mitochondrial lesions, including swelling, loss of cristae, and loss of inner and outer membranes, resulting in gross vacuolarization and deformation of ventricular mitochondria with a subsequent reduction in mitochondrial density. Expression of genes encoding various L-type Ca 2+ channel proteins (Cacnb2) and cardiac muscle proteins (Myl2 and Atp2a1) were downregulated in GK-HFD compared with GK-LFD rats. Structural lesions and changed expression of genes encoding various cardiac muscle proteins might partly underlie the altered time course of myocyte shortening and relaxation in myocytes from GK-HFD compared with GK-LFD rats. A variety of diastolic and systolic dysfunctions have been widely reported in type 2 diabetic patients, and the severity of abnormalities depends on the patients' age and the duration of diabetes. Haemodynamic abnormalities include reduced left ventricular ejection fraction, impaired myocardial velocity at early diastole, abnormal relaxation during the early filling phase, prolonged isovolumetric relaxation, lower peak systolic and early diastolic velocity, impaired diastolic relaxation and filling and reduced peak filling rate (von Bibra et al. 2005;Dounis et al. 2006;Markuszewski et al. 2006;Sharman et al. 2007). The GotoKakizaki (GK) rat is a genetic animal model of type 2 diabetes, which was created by selective breeding of an outbred colony of Wistar rats with selection for high

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Section: Electron Microscopymentioning

confidence: 99%

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Howarth¹,

Qureshi²,

Sobhy³

et al. 2011

Experimental Physiology

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“…Several reports have demonstrated structural and functional alterations in the lacrimal gland associated with aging in animals. [18][19][20][21] In humans, various increasing morphological changes have also been observed to more frequently occur as an individual ages. As an example, acinar atrophy and fibrosis initially occur in younger patients, with the incidence increasing over time.…”

Section: Changes In the Lacrimal Gland With Agingmentioning

confidence: 99%

Effect of Calorie Restriction on Change in Lacrimal Gland With Age

Kawashima

Tsubota²

2011

Cornea

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Rapid growth in the number of dry eye syndrome patients has been observed worldwide. Increased life span is considered to be at least part of the reason for this because there is a close association between aging and decreased secretory function in the lacrimal gland. Recent advances have led to a new way of thinking about intervention in the aging process. Calorie restriction (CR) is believed to retard functional decline in various organs with age. We hypothesized that CR could prevent age-related lacrimal dysfunction. In this paper, we begin by reviewing the epidemiology of dry eye syndrome and explaining how aging affects lacrimal gland function. We then introduce a possible therapeutic approach to this problem, intervention by means of CR. Finally, suggestions are made for further prospective research that would elucidate the molecular mechanisms by which CR maintains lacrimal gland function.

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“…Given the similar histologic appearance of parotid salivary and lacrimal gland, it is tempting to speculate on a possible association, although we have no evidence to substantiate this. So-called serous changes have been reported in the lacrimal glands of aged rats 6 but do not feature in the published accounts of spontaneous findings in Beagles.…”

Section: Discussionmentioning

confidence: 91%

Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs

et al. 2015

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AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data.Keywords aging, background lesions, beagle, dog, clinical pathology, incidental findings, histopathology, toxicology studies While Beagle dogs were originally developed for hunting, they have been extensively used as a species for the toxicity testing of agrochemicals and pharmaceuticals. 2,4,22 Olson 21 provided data that supported the use of nonrodents in safety testing by comparing human toxicities with those identified in animals. The results showed the true positive concordance rate of 71% for rodent and nonrodent species combined, with nonrodents alone being predictive for 63% of human toxicities.Chronic toxicity testing in dogs is normally confined to studies with a maximum duration of 1 year, with animals typically being 6 to 12 months old at study start. As a result, publications detailing the incidence of spontaneous pathology findings in Beagles are confined to animals no older than 2 years. 12,[16][17][18]28 While chronic lifetime studies in Beagle dogs have been undertaken at the Lovelace Respiratory Research Institute (LLRI), 19 published data from these studies does not include detailed observations of the spontaneous pathology noted in dogs aged between 2 and 5 years.AstraZeneca had a cohort of older beagle dogs available for use on routine toxicity studies, with the age of all animals exceeding the upper age limit of Beagles routinely used in toxicity testing (>24 months), raising concerns about a lack of suitable age-and strain-matched historical control data and potential impact on the interpretation of histopathology findings.AstraZeneca has a commitment to fully implement the principles of replacement, reduction, and refinement (3 Rs) for the use of animals in research; therefore, the aim of the study described here was to generate a complete ''guideline compliant'' set of hematology, clinical chemistry, and ...

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Age-related changes in morphology and secretory responses of male rat lacrimal gland

Cited by 48 publications

References 22 publications

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Effect of Calorie Restriction on Change in Lacrimal Gland With Age

Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs

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