Scaling and maintenance of corneal thickness during aging

Inomata, Takenori; Mashaghi, Alireza; Hong, Jiaxu; Dana, Reza

doi:10.1371/journal.pone.0185694

Cited by 18 publications

(11 citation statements)

References 36 publications

(30 reference statements)

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“…While the anterior corneal epithelium thickened from 8 to 20 weeks in both strains, it was thinner in BXSB-Yaa than in BXSB at 28 weeks. Consistent with our results, the anterior corneal epithelium thickens with ageing in healthy mice, 33 and dry eye model mice have thinner corneal epithelium due to cell injuries than healthy controls. 10 A previous study showed that tear film instability could cause potential damage to the ocular surface.…”

Section: Discussionsupporting

confidence: 91%

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Hiraishi

Masum

Namba

et al. 2020

Exp Biol Med (Maywood)

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The tear film covers the cornea, and its abnormalities (including immunological) induce dry eye. Using autoimmune disease model mice, BXSB/MpJ- Yaa (BXSB-Yaa), histopathological changes in the eye and tear-secreting tissues were examined using histopathology, immunohistochemistry, and electron microscopy at 8, 20, and 28 weeks for early, middle, and late disease stages. Early and middle stage BXSB-Yaa showed increased serum autoantibody and spleen weight-to-body weight (S/B) ratio, respectively, and higher tear volume than controls, BXSB/MpJ (BXSB), at early stages, which decreased with ageing and negatively correlated with autoimmune disease indices. Smaller Meibomian gland acini, intraorbital lacrimal glands, and Harderian gland acinar cells were seen in late stage BXSB-Yaa than in BXSB; the latter two indices decreased with ageing and negatively correlated with the S/B ratio. Cell infiltration occurred in the middle stage BXSB-Yaa extraorbital lacrimal gland, and acinar cells were smaller than BXSB. The conjunctival goblet cells decreased from early to middle stages in both strains, but in BXSB-Yaa, they increased at late stages with a partial lack of microvilli on the cornea and were inversely altered with anterior epithelium thickness through ageing, suggesting that they compensated for anterior epithelium damage. In conclusion, the tear film was unstable due to an autoimmune disease condition in BXSB-Yaa. Impact statement Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren’s syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.

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Section: Discussionsupporting

confidence: 91%

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Hiraishi

Masum

Namba

et al. 2020

Exp Biol Med (Maywood)

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“…Especially in the case of DED, non-contact measurement methods are preferred because the patients with DED are more susceptible to corneal epithelial damage and infection [26]. Recently, several units of non-contact tonometry and pachymetry have been developed for clinical and small-animal imaging [27]. Pentacam (OCULUS, Optikgerate GmbH, Wetzlar, Germany), a rotating Scheimpflug camera, and anterior segment optical coherence tomography (ASOCT) determine the CCT, TCT, and the thinnest point of the cornea.…”

Section: Introductionmentioning

confidence: 99%

Comparison of corneal thickness in patients with dry eye disease using the Pentacam rotating Scheimpflug camera and anterior segment optical coherence tomography

et al. 2020

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The purpose of this study was to compare central corneal thickness, thinnest corneal thickness, and the thinnest point of the cornea between Pentacam and anterior segment optical coherence tomography (ASOCT) in patients with dry eye disease (DED). This cross-sectional study included 195 participants between November 2015-June 2017. DED was diagnosed using the Asia Dry Eye Society criteria and further divided into mild and severe DED based on kerato-conjunctival vital staining. Central corneal thickness, thinnest corneal thickness, and the thinnest point of the cornea measured by Pentacam and ASOCT were compared, and Pearson's correlation coefficients were estimated. The differences in central corneal thickness and the thinnest corneal thickness between Pentacam and ASOCT were analysed using Bland-Altman and multivariate regression analyses adjusted for age and sex. This study included 70 non-DED subjects and 52 patients with mild and 73 with severe DED. The Pentacam and ASOCT measurements of central corneal thickness and thinnest corneal thickness were strongly correlated, but the respective values were higher when measured with Pentacam. The Bland-Altman analysis revealed differences in central corneal thickness (non DED, 11.8; mild DED, 13.2; severe DED, 19.6) and in thinnest corneal thickness (non DED, 13.1; mild DED, 13.4; severe DED, 20.7). After adjusting for age and sex, the differences in central corneal thickness (β = 7.029 μm, 95%CI 2.528-11.530) and thinnest corneal thickness (β = 6.958 μm, 95%CI 0.037-13.879) were significantly increased in the severe-DED group. The distribution of the thinnest point of the cornea in the cornea's inferior temporal quadrant between Pentacam and ASOCT deviated in severe DED (Pentacam: 90.4% vs. ASOCT: 83.6%). Clinicians should consider that there were significant differences in corneal-morphology assessment between the measurements with Pentacam and ASOCT in severe DED.

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“…11,61,62 Thus, although endothelial cell density was not quantified in the current study, it is likely that the observed increase in stromal thickness could be explained by an age-related decline in endothelial cell density. Inomata et al 19 also reported an increase in the corneal thickness, but no change to epithelial thickness, of BALB/c mice at 14 months of age. This disparity may be accounted for by the genetic variation between different mouse strains and different ages.…”

Section: Discussionmentioning

confidence: 92%

“…However, there remains inconsistency with respect to the reported impact of aging on other ocular surface parameters, such as corneal thickness, where some studies have reported no age-related changes, 17,18 and others have shown an increased thickness compared with young mice. 19 In addition, the effects of aging on corneal immune responses, in particular the number, distribution, and morphology of resident epithelial dendritic cells (DCs), is unclear. The normal corneal epithelium has a resident population of DCs that have been well characterized in both humans and rodents.…”

mentioning

confidence: 99%

The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice

Silva

Hill

Downie

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Aging is a risk factor for dry eye disease. The aim of this study was to investigate if aging is associated with a range of signs of dry eye disease, including tear hyperosmolarity, reduced nerve density, and increased dendritic cell number, in mice. METHOD. Healthy C57BL/6 female mice, aged 2 months (young, n ¼ 10) and 22 months (aged, n ¼ 11) were used. Clinical assessments included corneal sensitivity (Cochet-Bonnet esthesiometry), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer), and corneal thickness (optical coherence tomography). The sum length of the corneal superficial terminals and sub-basal nerves, density of vertical nerve projections, and density and tree area of resident epithelial dendritic cells, were assessed using immunofluorescence and confocal microscopy. RESULTS. Aged mice had significantly higher tear secretion, lower corneal sensitivity, and a thicker corneal stroma but thinner epithelium. There was no significant intergroup difference for tear osmolarity. Aged mice showed a significantly lower sum length of nerves in the superficial terminals and sub-basal plexus, relative to young mice. Dendritic cell density and morphology were similar in both groups. CONCLUSIONS. In mice, aging is associated with higher tear secretion and corneal epithelial thinning, together with lower corneal nerve density and sensitivity. However, aging was not significantly associated with changes to tear osmolarity or dendritic cell density or size, despite a significant reduction in total nerve length. These findings demonstrate that aged mice exhibit some changes to ocular surface parameters that parallel the anomalies evident in dry eye disease.

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Scaling and maintenance of corneal thickness during aging

Cited by 18 publications

References 36 publications

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Comparison of corneal thickness in patients with dry eye disease using the Pentacam rotating Scheimpflug camera and anterior segment optical coherence tomography

The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice

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