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Open Access Basic Research Issue
4D label-free proteomic analysis of vitreous from patients with rhegmatogenous retinal detachment
International Journal of Ophthalmology 2023, 16(4): 523-531
Published: 18 April 2023
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AIM

To identify metabolites, proteins, and related pathways involved in the etiology of rhegmatogenous retinal detachment (RRD) for use as biomarkers in diagnosing and treating RRD.

METHODS

Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was performed using the four-dimensional label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, and protein interactions were analyzed.

RESULTS

Nine specimens were subjected to proteomic analysis. In total, 161 proteins were identified as differentially expressed proteins (DEPs), including 53 upregulated proteins and 108 downregulated proteins. GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms. Moreover, KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs. Finally, the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion, apoptosis, inflammation and immune responses, correct protein folding, and glycolysis.

CONCLUSION

Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD. This study reveals increased expression levels of proteins related to heat shock protein content, glycolysis, and inflammatory responses in RRD. Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.

Open Access Clinical Research Issue
Clinical and multimodal imaging features of acute macular neuroretinopathy lesions following recent SARS-CoV-2 infection
International Journal of Ophthalmology 2023, 16(5): 755-761
Published: 18 May 2023
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AIM

To describe the clinical characteristics of eyes using multimodal imaging features with acute macular neuroretinopathy (AMN) lesions following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

METHODS

Retrospective case series study. From December 18, 2022 to February 14, 2023, previously healthy cases within 1-week infection with SARS-CoV-2 and examined at Tianjin Eye Hospital to confirm the diagnosis of AMN were included in the study. Totally 5 males and 9 females [mean age: 29.93±10.32 (16-49)y] were presented for reduced vision, with or without blurred vision. All patients underwent best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundoscopy. Simultaneously, multimodal imagings fundus photography (45° or 200° field of view) was performed in 7 cases (14 eyes). Near infrared (NIR) fundus photography was performed in 9 cases (18 eyes), optical coherence tomography (OCT) in 5 cases (10 eyes), optical coherence tomography angiography (OCTA) in 9 cases (18 eyes), and fundus fluorescence angiography (FFA) in 3 cases (6 eyes). Visual field was performed in 1 case (2 eyes).

RESULTS

Multimodal imaging findings data from 14 patients with AMN were reviewed. All eyes demonstrated different extent hyperreflective lesions at the level of the inner nuclear layer and/or outer plexus layer on OCT or OCTA. Fundus photography (45° or 200° field of view) showed irregular hypo-reflective lesion around the fovea in 7 cases (14 eyes). OCTA demonstrated that the superficial retinal capillary plexus (SCP) vascular density, deep capillary plexus (DCP) vascular density and choriocapillaris (CC) vascular density was reduced in 9 case (18 eyes). Among the follow-up cases (2 cases), vascular density increased in 1 case with elevated BCVA; another case has vascular density decrease in one eye and basically unchanged in other eye. En face images of the ellipsoidal zone and interdigitation zone injury showed a low wedge-shaped reflection contour appearance. NIR image mainly show the absence of the outer retinal interdigitation zone in AMN. No abnormal fluorescence was observed in FFA. Corresponding partial defect of the visual field were visualized via perimeter in one case.

CONCLUSION

The morbidity of SARS-CoV-2 infection with AMN is increased. Ophthalmologists should be aware of the possible, albeit rare, AMN after SARS-CoV-2 infection and focus on multimodal imaging features. OCT, OCTA, and infrared fundus phase are proved to be valuable tools for detection of AMN in patients with SARS-CoV-2.

Open Access Clinical Research Issue
Detection of macular ganglion cell complex loss and correlation with choroidal thickness in chronic and recurrent central serous chorioretinopathy
International Journal of Ophthalmology 2023, 16(4): 579-588
Published: 18 April 2023
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AIM

To investigate the association of ganglion cell complex thickness (GCCt), global loss volume percentage (GLV%), and focal loss volume percentage (FLV%) with structural and functional findings among patients with chronic central serous chorioretinopathy (CCSC) and recurrent central serous chorioretinopathy (RCSC) by optical coherence tomography (OCT).

METHODS

Among 29 patients with monocular affected central serous chorioretinopathy (CSC), 15 had CCSC, and 14 had RCSC. The GCCt, FLV%, GLV%, and subfoveal choroidal thickness (SFCT) and sublesional choroidal thickness (SLCT) values were determined using OCT, and the association of these characteristics with neural structure parameters, choroidal morphology, features and functional alterations were estimated for the CCSC and RCSC patients.

RESULTS

In CCSC, the affected eyes had significantly lower GCCt values than the fellow eyes in the macular regions (all P<0.05), with the highest GCCt observed in the inferior area. A significant association was found between the GCCt in different regions and the change in best corrected visual acuity (BCVA; r=-0.696; -0.695; -0.694, P<0.05) in CCSC patients. A statistically significant moderate negative correlation indicated that long-term CCSC was associated with greater differences in the GCCt in different regions between affected and fellow eyes (r=-0.562; r=-0.556; r=0.525, P<0.05). Additionally, observation of thickened SFCT was associated with a worse FLV% (r=0.599; r=0.546, P<0.05) in both groups. Similarly, thickened SLCT was associated with FLV% in RCSC patients (r=0.544, P<0.05).

CONCLUSION

The distribution and GCCt are associated with the duration and visual outcomes of CCSC, whereas there is no correlation among RCSC patients. FLV% may be instrumental in differentiating the various outer choroidal vessels (pachyvessels) in long-term CSC. These results suggest that neural structure parameters may aid in estimating and predicting the recovery of altered morphology and function in CCSC and RCSC patients.

Open Access Basic Research Issue
Effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization in high myopia mice
International Journal of Ophthalmology 2023, 16(7): 1034-1040
Published: 18 July 2023
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AIM

To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization (CNV) in high myopia mice.

METHODS

The C57BL/6J mice were deprived of the right eye for 4wk, and the high myopia was diagnosed by optometry, the diopter was less than -6.00 D, and CNV was induced by 532 nm laser. The changes of dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), and vascular endothelial growth factor A (VEGFA) were detected by Western blot technology at 0.5, 1, 2h, and 7d after 0.01%, 0.05%, and 0.1% atropine eye drops, respectively, the area of CNV was measured.

RESULTS

Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group, and the higher the concentration, the more significant the inhibitory effect (P<0.05).

CONCLUSION

The 0.01%, 0.05%, 0.1% atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1, and the effect of 0.05% and 0.1% atropine eye drops is more significant.

Open Access Basic Research Issue
Human umbilical cord mesenchymal stem cells derived-exosomes on VEGF-A in hypoxic-induced mice retinal astrocytes and mice model of retinopathy of prematurity
International Journal of Ophthalmology 2024, 17(7): 1238-1247
Published: 18 July 2024
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AIM

To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP).

METHODS

Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information.

RESULTS

The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion.

CONCLUSION

In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

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