RESUMO
PURPOSE: To investigate the impact of exercise and mask-wearing on retinal microvasculature using optical coherence tomography angiography (OCTA). METHODS: A total of 30 healthy volunteers were enrolled and tasked with physical exercise to reach 75-80 % maximum heart rates. Swept-source OCTA was performed on the macular region and optic nerve head (ONH) in participants with no mask, surgical mask, or N95 mask at quiescent conditions (Step 1) and 0 min, 10 min, 20 min, and 30 min post-exercise (Steps 2-5, respectively). The functional vessel density (VD), including the superficial and deep plex (SP and DP) in the macular area and the superficial plex (SP), nerve fiber plex, and small vessels in the optic nerve head, were measured. RESULTS: Under quiescent conditions, the functional VD of SP and DP exhibited significant reduction with surgical and N95 masks in the foveal area (P < 0.05). In step 2 (immediately after training) with or without masks, functional VD of SP and nerve fiber both showed significant reduction in the inside disc and peripapillary area, small functional VD of nerve fiber in the ONH showed significant reduction in peripapillary area (P < 0.05). These changes had been recovered in Step 5 (30 min post-exercise) in all groups (no-mask, surgical mask and N95 mask groups) (P > 0.05). CONCLUSIONS: Mask-wearing and physical exercise reduce retinal functional VD in macular and ONH areas. The retinal vasoconstriction induced by exercise tends to recover after rest for approximately 30 min. Our research provides insights into mask-wearing and physical exercise's immediate retinal microvasculature effects, hinting at systemic microvascular changes.
Assuntos
Exercício Físico , Voluntários Saudáveis , Máscaras , Microcirculação , Microvasos , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Vasos Retinianos/diagnóstico por imagem , Masculino , Adulto , Feminino , Fatores de Tempo , Adulto Jovem , Microvasos/fisiologia , Microvasos/diagnóstico por imagem , Valor Preditivo dos Testes , Densidade Microvascular , Disco Óptico/irrigação sanguínea , Recuperação de Função FisiológicaRESUMO
Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.
Assuntos
Neovascularização de Coroide , Modelos Animais de Doenças , Macrófagos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Semaforinas , Transdução de Sinais , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP , Animais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Camundongos , Macrófagos/metabolismo , Quinases Associadas a rho/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Western Blotting , Masculino , AngiofluoresceinografiaRESUMO
Purpose: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease with largely unknown intraocular pathogenesis. Herein, we determined the presence of SARS-CoV-2-specific ribonucleic acid (RNA) and virus-associated antibodies in the vitreous humor of people who have recently recovered from SARS-CoV-2 infection. Design: This cross-sectional study included 33 patients (33 eyes) who have recently recovered from SARS-CoV-2 infection. Vitreous humor and blood serum samples were tested for the SARS-CoV-2 RNA and virus-associated antibodies. Results: Among 33 participants, blood serum and vitreous humor were all tested negative for SARS-CoV-2 RNA. SARS-CoV-2-specific IgM was detected in 87.88 % (29/33) patients in blood serum and 6.10 % (2/33) in vitreous humor; SARS-CoV-2-specific IgG was detected in 96.97 % (32/33) patient in blood serum and 81.82 % (27/33) in vitreous humor. Statistical significance was found for IgM expression between blood serum and vitreous humor (P < 0.01), while IgG was not (P = 0.11). The days after recovery were statistically longer both in IgM-positive blood serum samples group and IgG-positive vitreous humor samples group compared with negative samples of each group (P < 0.01). Additionally, no statistical difference could be detected in antibody expression in vitreous humor between different groups divided on the condition of the risk of blood-retina-barrier (BRB) failure (P = 0.49 for IgM; P = 0.37 for IgG). Conclusion: After recovering from COVID-19, no SARS-CoV-2 RNA was detected in vitreous humor, but anti-CoV-2 IgM was detected in 6.1 % and IgG in approximately 80 % of vitreous humor samples of participants. We also found that the positivety rate of SARS-CoV-2-specific antibodies in the blood serum and vitreous humor were both correlated with the days after recovery since the infection.
RESUMO
Purpose: The present study aimed to evaluate the effect of acrizanib, a small molecule inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), on physiological angiogenesis and pathological neovascularization in the eye and to explore the underlying molecular mechanisms. Methods: We investigated the potential role of acrizanib in physiological angiogenesis using C57BL/6J newborn mice, and pathological angiogenesis using the mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. Moreover, vascular endothelial growth factor (VEGF)-treated human umbilical vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying acrizanib's antiangiogenic effects. Results: The intravitreal injection of acrizanib did not show a considerable impact on physiological angiogenesis and retinal thickness, indicating a potentially favorable safety profile. In the mouse models of OIR and CNV, acrizanib showed promising results in reducing pathological neovascularization, inflammation, and vascular leakage, indicating its potential efficacy against pathological angiogenesis. Consistent with in vivo results, acrizanib blunted angiogenic events in VEGF-treated HUVECs such as proliferation, migration, and tube formation. Furthermore, acrizanib inhibited the multisite phosphorylation of VEGFR2 to varying degrees and the activation of its downstream signal pathways in VEGF-treated HUVECs. Conclusions: This study suggested the potential efficacy and safety of acrizanib in suppressing fundus neovascularization. Acrizanib functioned through inhibiting multiple phosphorylation sites of VEGFR2 in endothelial cells to different degrees. Translational Relevance: These results indicated that acrizanib might hold promise as a potential candidate for the treatment of ocular vascular diseases.