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A mouse model of corneal endothelial decompensation using cryoinjury.

Han SB, Ang H, Balehosur D, Peh G, Chaurasia SS, Tan DT, Mehta JS - Mol. Vis. (2013)

Bottom Line: IOP remained within normal range in group A, but increased significantly with time in group B (p=0.011 at day 1, 0.038 at day 3, 0.026 at day 14, and 0.008 at day 21).Live/dead cell assay, hematoxylin and eosin staining, and scanning electron microscopy revealed successful ablation of corneal endothelial cells and absence of regeneration in both groups.One cycle of cryoinjury was safer than three, while both were equally effective in inducing bullous keratopathy.

View Article: PubMed Central - PubMed

Affiliation: Singapore National Eye Centre, Singapore.

ABSTRACT

Purpose: To develop a mouse model of bullous keratoplasty and evaluate the safety and efficacy of cryoinjury-induced corneal endothelial decompensation.

Methods: Transcorneal freezing was performed on the right eye of each mouse. One cycle of cryoinjury was performed in 18 eyes (group A), and three cycles were performed in 17 eyes (group B). Pachymetry and intraocular pressure (IOP) measurements were done preoperatively, as well as at 1, 3, 7, 14, and 21 days after cryoinjury. At each post-cryoinjury time point, three mice from each group were euthanized, and the corneas underwent histology and electron microscopy.

Results: In both groups, significant corneal edema was noted at post-cryoinjury day 1, which was maintained throughout the study period. IOP remained within normal range in group A, but increased significantly with time in group B (p=0.011 at day 1, 0.038 at day 3, 0.026 at day 14, and 0.008 at day 21). In group B, serious complications including hyphema (one case), severe iridocorneal adhesion (15 cases), and total cataract (three cases) were detected, while only mild iridocorneal adhesion (four cases) and cataract (three cases) were noted in group A. Live/dead cell assay, hematoxylin and eosin staining, and scanning electron microscopy revealed successful ablation of corneal endothelial cells and absence of regeneration in both groups. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay showed that apoptosis was mainly confined to the posterior stroma and endothelium in group A, while severe apoptosis was observed throughout all layers of the cornea in group B.

Conclusions: One cycle of cryoinjury was safer than three, while both were equally effective in inducing bullous keratopathy. This cryoinjury mouse model of bullous keratopathy was a consistently reproducible model that can be used for further studies on endothelial cell damage and rescue therapy.

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Representative photos showing complications following the cryoinjury. In group A, mild peripheral iridocorneal adhesion (left) and mild cataract (middle and right) were found. In group B, serious complications including severe anterior chamber inflammation and cataract (left), total iridocorneal adhesion (middle), and hyphema (right) were detected.
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f3: Representative photos showing complications following the cryoinjury. In group A, mild peripheral iridocorneal adhesion (left) and mild cataract (middle and right) were found. In group B, serious complications including severe anterior chamber inflammation and cataract (left), total iridocorneal adhesion (middle), and hyphema (right) were detected.

Mentions: In group A, mild peripheral iridocorneal adhesion occurred in four cases (from day 7 in two eyes and day 14 in two eyes). Mild cataract was noted in three cases (from day 7 in one eye and day 14 in two eyes). The eye that developed a cataract at day 7 resolved by day 14, but the remaining two cases were irreversible. In group B, severe AC inflammation was detected with AS-OCT in all mice at day 1, and hyphema was found in one case at day 7. Severe iridocorneal adhesion and resultant IOP increase were observed in 15 mice 3 days post-treatment. Development of irreversible cataract was found in all cases, of which three cases were total white cataract (Figure 3).


A mouse model of corneal endothelial decompensation using cryoinjury.

Han SB, Ang H, Balehosur D, Peh G, Chaurasia SS, Tan DT, Mehta JS - Mol. Vis. (2013)

Representative photos showing complications following the cryoinjury. In group A, mild peripheral iridocorneal adhesion (left) and mild cataract (middle and right) were found. In group B, serious complications including severe anterior chamber inflammation and cataract (left), total iridocorneal adhesion (middle), and hyphema (right) were detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675054&req=5

f3: Representative photos showing complications following the cryoinjury. In group A, mild peripheral iridocorneal adhesion (left) and mild cataract (middle and right) were found. In group B, serious complications including severe anterior chamber inflammation and cataract (left), total iridocorneal adhesion (middle), and hyphema (right) were detected.
Mentions: In group A, mild peripheral iridocorneal adhesion occurred in four cases (from day 7 in two eyes and day 14 in two eyes). Mild cataract was noted in three cases (from day 7 in one eye and day 14 in two eyes). The eye that developed a cataract at day 7 resolved by day 14, but the remaining two cases were irreversible. In group B, severe AC inflammation was detected with AS-OCT in all mice at day 1, and hyphema was found in one case at day 7. Severe iridocorneal adhesion and resultant IOP increase were observed in 15 mice 3 days post-treatment. Development of irreversible cataract was found in all cases, of which three cases were total white cataract (Figure 3).

Bottom Line: IOP remained within normal range in group A, but increased significantly with time in group B (p=0.011 at day 1, 0.038 at day 3, 0.026 at day 14, and 0.008 at day 21).Live/dead cell assay, hematoxylin and eosin staining, and scanning electron microscopy revealed successful ablation of corneal endothelial cells and absence of regeneration in both groups.One cycle of cryoinjury was safer than three, while both were equally effective in inducing bullous keratopathy.

View Article: PubMed Central - PubMed

Affiliation: Singapore National Eye Centre, Singapore.

ABSTRACT

Purpose: To develop a mouse model of bullous keratoplasty and evaluate the safety and efficacy of cryoinjury-induced corneal endothelial decompensation.

Methods: Transcorneal freezing was performed on the right eye of each mouse. One cycle of cryoinjury was performed in 18 eyes (group A), and three cycles were performed in 17 eyes (group B). Pachymetry and intraocular pressure (IOP) measurements were done preoperatively, as well as at 1, 3, 7, 14, and 21 days after cryoinjury. At each post-cryoinjury time point, three mice from each group were euthanized, and the corneas underwent histology and electron microscopy.

Results: In both groups, significant corneal edema was noted at post-cryoinjury day 1, which was maintained throughout the study period. IOP remained within normal range in group A, but increased significantly with time in group B (p=0.011 at day 1, 0.038 at day 3, 0.026 at day 14, and 0.008 at day 21). In group B, serious complications including hyphema (one case), severe iridocorneal adhesion (15 cases), and total cataract (three cases) were detected, while only mild iridocorneal adhesion (four cases) and cataract (three cases) were noted in group A. Live/dead cell assay, hematoxylin and eosin staining, and scanning electron microscopy revealed successful ablation of corneal endothelial cells and absence of regeneration in both groups. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay showed that apoptosis was mainly confined to the posterior stroma and endothelium in group A, while severe apoptosis was observed throughout all layers of the cornea in group B.

Conclusions: One cycle of cryoinjury was safer than three, while both were equally effective in inducing bullous keratopathy. This cryoinjury mouse model of bullous keratopathy was a consistently reproducible model that can be used for further studies on endothelial cell damage and rescue therapy.

Show MeSH
Related in: MedlinePlus