scholarly journals Ocular-Component-Specific miRNA Expression in a Murine Model of Lens-Induced Myopia

2019 ◽  
Vol 20 (15) ◽  
pp. 3629 ◽  
Author(s):  
Tanaka ◽  
Kurihara ◽  
Hagiwara ◽  
Ikeda ◽  
Mori ◽  
...  

To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation.

2021 ◽  
Vol 21 (4) ◽  
pp. 205-209
Author(s):  
M.M. Bikbov ◽  
◽  
O.I. Orenburkina ◽  
A.E. Babushkin ◽  
A.A. Fakhretdinova ◽  
...  

Eye disorders have a special place in diabetes since visual impairment has a significant effect on the quality of life. Therefore, determining risk factors and prognostic criteria for disease course are essential for developing strategies for early prevention of diabetic retinopathy (DR). This paper addresses studies on various aspects of DR in patients with myopia. It was demonstrated that DR arises, develops, and progresses in different ways under various axial lengths (AL). Thus, many authors report that DR barely occurs in high myopia. Some of them account for this phenomenon for poor blood circulation in a long myopic eye. Others refer to a significantly lower vascular endothelial growth factor (VEGF) concentration in longer eyes or eyes with myopic refraction. The third authors argue a focal disintegration of retinal pigment epithelium to eliminate metabolic end products through the choroid and sclera. As a result, neither acidosis nor venous congestion develops, and endothelial barrier function remains unaffected Keywords: diabetic retinopathy, myopia, axial length, vascular endothelial growth factor, emmetropia, hyperopia, diabetes. For citation: Bikbov M.M., Orenburkina O.I., Babushkin A.E., Fakhretdinova A.A. Effects of refraction and axial length on the development and progression of diabetic retinopathy. Russian Journal of Clinical Ophthalmology. 2021;21(4):205–209 (in Russ.). DOI: 10.32364/2311-7729- 2021-21-4-205-209.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Un Chul Park ◽  
Dae Joong Ma ◽  
Woon Hyung Ghim ◽  
Hyeong Gon Yu

AbstractIn this cross-sectional study, we investigated whether a foveal curvature affects the development of two major myopic macular complications, myopic traction maculopathy (MTM) and myopic choroidal neovascularization (mCNV). In high myopic eyes (axial length ≥ 26.5 mm, refractive error ≤ −6 diopters) with posterior staphyloma, three different parameters of foveal curvature (staphyloma height, coefficient a, and curvature index) calculated based on the retinal pigment epithelium hyperreflective line in spectral domain optical coherence tomography image were compared among the MTM (72 eyes), mCNV (58 eyes), and control (69 eyes) group. The three curvature parameters showed a significant correlation with each other (all P’s < 0.001). The axial length, refractive error, and staphyloma types were comparable among the groups, but the means of all three curvature parameters were significantly greater in the MTM group compared to the mCNV and control groups (all P’s < 0.001). Furthermore, the curvature parameters had a significant correlation with myopic severity in the MTM group, but not in the other groups. These results suggest that a steeper change of foveal curvature plays a role in the development of MTM but not mCNV in high myopes.


Author(s):  
Chia-Hung Lin ◽  
Chih-Sheng Chen ◽  
Yao-Chien Wang ◽  
En-Shyh Lin ◽  
Ching-Yao Chang ◽  
...  

The increased global incidence of myopia requires the establishment of therapeutic approaches. Previous studies have suggested that inflammation plays an important role in the development and progression of myopia. We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJE and PVE lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. Expression levels of IL-6, IL-8, and TNF-&alpha; were upregulated in retinal pigment epithelium (RPE) cells treated with IL-6 and TNF-&alpha;. FJ extract (FJE) + PV extract (PVE) reduced IL-6, IL-8, and TNF-&alpha; expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-&kappa;B) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-&alpha; expression levels in RPE cells treated with IL-6 and TNF-&alpha;. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-&alpha;. They also inhibited myopia-related transforming growth factor-beta (TGF)-&beta;1, matrix metalloproteinase (MMP)-2, and NF-&kappa;B expression while increasing type Ⅰ collagen expression. Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009458
Author(s):  
Swanand Koli ◽  
Cassandre Labelle-Dumais ◽  
Yin Zhao ◽  
Seyyedhassan Paylakhi ◽  
K. Saidas Nair

Precise regulation of ocular size is a critical determinant of normal visual acuity. Although it is generally accepted that ocular growth relies on a cascade of signaling events transmitted from the retina to the sclera, the factors and mechanism(s) involved are poorly understood. Recent studies have highlighted the importance of the retinal secreted serine protease PRSS56 and transmembrane glycoprotein MFRP, a factor predominantly expressed in the retinal pigment epithelium (RPE), in ocular size determination. Mutations in PRSS56 and MFRP constitute a major cause of nanophthalmos, a condition characterized by severe reduction in ocular axial length/extreme hyperopia. Interestingly, common variants of these genes have been implicated in myopia, a condition associated with ocular elongation. Consistent with these findings, mice with loss of function mutation in PRSS56 or MFRP exhibit a reduction in ocular axial length. However, the molecular network and cellular processes involved in PRSS56- and MFRP-mediated ocular axial growth remain elusive. Here, we show that Adamts19 expression is significantly upregulated in the retina of mice lacking either Prss56 or Mfrp. Importantly, using genetic mouse models, we demonstrate that while ADAMTS19 is not required for ocular growth during normal development, its inactivation exacerbates ocular axial length reduction in Prss56 and Mfrp mutant mice. These results suggest that the upregulation of retinal Adamts19 is part of an adaptive molecular response to counteract impaired ocular growth. Using a complementary genetic approach, we show that loss of PRSS56 or MFRP function prevents excessive ocular axial growth in a mouse model of early-onset myopia caused by a null mutation in Irbp, thus, demonstrating that PRSS56 and MFRP are also required for pathological ocular elongation. Collectively, our findings provide new insights into the molecular network involved in ocular axial growth and support a role for molecular crosstalk between the retina and RPE involved in refractive development.


2014 ◽  
Vol 13s5 ◽  
pp. CIN.S14074 ◽  
Author(s):  
Heuy-Ching Wang ◽  
Whitney A. Greene ◽  
Ramesh R. Kaini ◽  
Jane Shen-Gunther ◽  
Hung-I H Chen ◽  
...  

The purpose of this study is to characterize the microRNA (miRNA) expression profiles of induced pluripotent stem (iPS) cells and retinal pigment epithelium (RPE) derived from induced pluripotent stem cells (iPS-RPE). MiRNAs have been demonstrated to play critical roles in both maintaining pluripotency and facilitating differentiation. Gene expression networks accountable for maintenance and induction of pluripotency are linked and share components with those networks implicated in oncogenesis. Therefore, we hypothesize that miRNA expression profiling will distinguish iPS cells from their iPS-RPE progeny. To identify and analyze differentially expressed miRNAs, RPE was derived from iPS using a spontaneous differentiation method. MiRNA microarray analysis identified 155 probes that were statistically differentially expressed between iPS and iPS-RPE cells. Up-regulated miRNAs including miR-181c and miR-129–5p may play a role in promoting differentiation, while down-regulated miRNAs such as miR-367, miR-18b, and miR-20b are implicated in cell proliferation. Subsequent miRNA-target and network analysis revealed that these miRNAs are involved in cellular development, cell cycle progression, cell death, and survival. A systematic interrogation of temporal and spatial expression of iPS-RPE miRNAs and their associated target mRNAs will provide new insights into the molecular mechanisms of carcinogenesis, eye differentiation and development.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasuki Ito ◽  
Mari Ito ◽  
Takeshi Iwase ◽  
Keiko Kataoka ◽  
Kazuhisa Yamada ◽  
...  

AbstractPachyvessels are pathologically dilated large choroidal vessels and are associated with the pathogenesis of several pachychoroid-related disorders, including central serous chorioretinopathy. We aimed to investigate the prevalence of and risk factors for pachyvessels in the Japanese population. We included 316 participants (aged ≥ 40 years) with normal right eyes. The presence of pachyvessels (vertical diameter > 300 µm, distance to the retinal pigment epithelium < 50 µm) was determined using 6 × 6 mm macular swept-source optical coherence tomography images, and associated risk factors were investigated. Subfoveal choroidal thickness was measured, and its associated risk factors investigated. The overall prevalence of pachychoroids was 9.5%. Regression analysis showed that a younger age, shorter axial length, male sex, and smoking were significantly associated with the presence of pachyvessels (p = 0.047; odds ratio [OR] 0.96 per year, p = 0.021; OR 0.61 per 1 mm, p = 0.012; OR 3.08 vs. female, and p = 0.011; OR 3.15 vs. non-smoker, respectively) and greater choroidal thickness (p < 0.001, p < 0.001, p < 0.003, and p < 0.017, respectively). The results were consistent with other research findings which showed that pachychoroid-related disorders such as central serous chorioretinopathy were associated with younger age, male sex, shorter axial length, and smoking. Smoking may be associated with choroidal circulatory disturbance in the Japanese population.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jacqueline Chua ◽  
Yih Chung Tham ◽  
Bingyao Tan ◽  
Kavya Devarajan ◽  
Florian Schwarzhans ◽  
...  

AbstractWe characterized the age-related changes of the intra-retinal layers measured with spectral-domain optical coherence tomography (SD-OCT; Cirrus high-definition OCT [Carl Zeiss Meditec]. The Singapore Epidemiology of Eye Diseases is a population-based, cross-sectional study of Chinese, Malays and Indians living in Singapore. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used for intra-retinal layer segmentation and mean thickness of 10 intra-retinal layers rescaled with magnification correction using axial length value. Linear regression models were performed to investigate the association of retinal layers with risk factors. After excluding participants with history of diabetes or ocular diseases, high-quality macular SD-OCT images were available for 2,047 participants (44–89 years old). Most of the retinal layers decreased with age except for foveal retinal nerve fiber layer (RNFL) and the inner/outer segments of photoreceptors where they increased with age. Men generally had thicker retinal layers than women. Chinese have the thickest RNFL and retinal pigment epithelium amongst the ethnic groups. Axial length and refractive error remained correlated with retinal layers in spite of magnification correction. Our data show pronounced age-related changes in retinal morphology. Age, gender, ethnicity and axial length need be considered when establishing OCT imaging biomarkers for ocular or systemic disease.


2018 ◽  
Vol 29 (3) ◽  
pp. 287-294
Author(s):  
Arnaud Messerlin ◽  
Mathieu Greth ◽  
Tristan Bourcier ◽  
Arnaud Sauer ◽  
Claude Speeg-Schatz ◽  
...  

Purpose: The objective of this study was to determine whether the dark adaptation time was longer in highly myopic patients than in emmetropic patients and whether there was a correlation between dark adaptation results and axial length. Patients and methods: We conducted a retrospective study that included highly myopic patients with −6.00 dioptres or more, matched to emmetropic control patients of the same age. All patients underwent an automated adaptometry protocol that calculates the rod intercept that reflects rod-mediated dark adaptation. Axial length was measured. Colour photographs were taken to look for retinal atrophic lesions. Results: A total of 25 highly myopic patients and 25 control patients were included. The mean rod intercept was 4.38 (±1.60) min in the myopic patients and 4.27 (±1.41) min in the control patients. This difference was not statistically significant ( p = 0.79). However, in myopic patients, the longer the axial length was, the longer the dark adaptation time was ( p = 0.0003). In addition, dark adaptation was significantly longer in myopic patients with retinal pigment epithelium atrophy than in patients without lesions ( p = 0.0398). Conclusion: In this study, dark adaptation time did not significantly differ between myopic patients and controls but was correlated with axial length in patients with severe myopia and was significantly longer in the presence of retinal pigment epithelium atrophic lesions.


2016 ◽  
Vol 95 (1) ◽  
pp. e22-e28 ◽  
Author(s):  
Jost B. Jonas ◽  
Kyoko Ohno-Matsui ◽  
Leonard Holbach ◽  
Songhomitra Panda-Jonas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shefali B. Jonas ◽  
Songhomitra Panda-Jonas ◽  
Jost B. Jonas ◽  
Rahul A. Jonas

AbstractTo assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24–89 years; axial length: 25.5 ± 3.1 mm; range: 20–37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0–31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch’s membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.


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