Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Srinivasalu, Nethrajeith; McFadden, Sally A; Medcalf, Callan; Fuchs, Lena; Chung, Jessica; Philip, Gayle K.; Richardson, Andrea J.; Riaz, Moeen; Baird, Paul N.

doi:10.1167/iovs.16-21278

Cited by 33 publications

(13 citation statements)

References 42 publications

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“…The refractive state of 11week-old guinea pigs was stabilized in the mild hyperopic eye. The FDM model has been widely used in experimental research on myopia [25,26]. Studies have shown that guinea pigs have the characteristic of high sensitivity to FD and become ideal animal models of experimental myopia [27].…”

Section: Discussionmentioning

confidence: 99%

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Deng

Zhao

et al. 2020

BMC Ophthalmol

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Background: To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. Methods: Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results: After 8 weeks of stitching, the refractive errors of Group II changed from (+ 3.59 ± 0.33) D to (− 7.96 ± 0.55) D, and these values were significantly higher than those of Group I (+ 0.89 ± 0.32) D and Group III (− 0.55 ± 0.49) D (P < 0.05). The vitreous chamber depth (4.12 ± 0.13) mm and axial length (8.93 ± 0.22) mm of Group II were significantly longer than those of Group I [(3.71 ± 0.23) mm and (7.95 ± 0.37) mm, respectively] and Group III [(3.93 ± 0.04) mm and (8.01 ± 0.15) mm, respectively] (P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). Conclusions: These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.

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Section: Discussionmentioning

confidence: 99%

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Deng

Zhao

et al. 2020

BMC Ophthalmol

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“…Myopic scleral remodeling is a dynamic process that leads to reduced collagen content and thinner collagen fiber bundles, followed by scleral thinning and extension [6,7]. Although several molecules, such as transforming growth factor-beta (TGF-β) [8][9][10], dopamine [11,12], retinoic acid [13,14], and cAMP [15,16], are known to be involved in scleral changes in myopia, the mechanism underlying myopic scleral remodeling has not been fully elucidated. Clarifying these events is necessary to develop effective therapeutic interventions targeting scleral remodeling and limiting the development of myopia.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Regulates Scleral Remodeling in a Guinea Pig Model of Form-Deprivation Myopia

Zhu

Chen

Yuan

et al. 2020

Journal of Ophthalmology

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Purpose. This study aimed to investigate the role of endoplasmic reticulum (ER) stress in scleral remodeling in a guinea pig model of form-deprivation myopia (FDM). Methods. Guinea pigs were form deprived to induce myopia. ER ultrastructural changes in the sclera were examined by transmission electron microscopy (TEM). The protein levels of ER stress chaperones, including GRP78, CHOP, and calreticulin (CRT), were analyzed by western blotting at 24 hours, 1 week, and 4 weeks of FD. Scleral fibroblasts from guinea pigs were cultured and exposed to the ER stress inducer tunicamycin (TM) or the ER stress inhibitor 4-phenylbutyric acid (4-PBA). CRT was knocked down by lentivirus-mediated CRT shRNA transfection. The expression levels of GRP78, CHOP, TGF-β1, and COL1A1 were analyzed by qRT-PCR or western blotting. Results. The sclera of FDM eyes exhibited swollen and distended ER at 4 weeks, as well as significantly increased protein expression of GRP78 and CRT at 1 week and 4 weeks, compared to the sclera of the control eyes. In vitro, TM induced ER stress in scleral fibroblasts, which was suppressed by 4-PBA. The mRNA expression of TGF-β1 and COL1A1 was upregulated after TM stimulation for 24 hours, but downregulated for 48 hours. Additionally, change of TGF-β1 and COL1A1 transcription induced by TM was suppressed by CRT knockdown. Conclusions. ER stress was an important modulator which could influence the expression of the scleral collagen. CRT might be a new target for the intervention of the FDM scleral remodeling process.

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“…The refractive state of 11-week-old guinea pigs was stabilized in the mild hyperopic eye. The FDM model has been widely used in experimental research on myopia [25,26]. Studies have shown that guinea pigs have the characteristic of high sensitivity to FD and become ideal animal models of experimental myopia [27].…”

Section: Discussionmentioning

confidence: 99%

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Deng

Zhao

et al. 2020

Preprint

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Background: To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation.Methods: Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results: After eight weeks of stitching, the refractive errors of Group II changed from (+3.59±0.33) D to (-7.96±0.55) D, and these values were significantly higher than those of Group I (+0.89±0.32) D and Group III (-0.55±0.49) D (P < 0.05). The vitreous chamber depth (4.12±0.13) mm and axial length (8.93±0.22) mm of Group II were significantly longer than those of Group I [(3.71±0.23) mm and (7.95±0.37) mm, respectively] and Group III [(3.93±0.04) mm and (8.01±0.15) mm, respectively](P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). Conclusions:These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.

show abstract

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Cited by 33 publications

References 42 publications

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Endoplasmic Reticulum Stress Regulates Scleral Remodeling in a Guinea Pig Model of Form-Deprivation Myopia

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

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