Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia–Reperfusion in the Eyes of Sprague Dawley Rats

Takács, Barbara; Szilágyi, Anna; Priksz, Dániel; Bombicz, Mariann; Szabó, Adrienn Mónika; Pelles-Taskó, Beáta; Rusznyák, Ágnes; Haimhoffer, Ádám; Gesztelyi, Rudolf; Szilvássy, Zoltán; Juhász, Béla; Varga, Balázs

doi:10.3390/biomedicines12030637

Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats

Szilágyi,

Takács,

Szekeres

et al. 2024

GeroScience

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Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens—voluntary (recreational-type) and forced (high-intensity)—on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations.

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Silicone Wire Embolization-induced Acute Retinal Artery Ischemia and Reperfusion Model in Mouse: Gene Expression Provides Insight into Pathological Processes

Wang,

Li,

Feng

et al. 2024

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Acute retinal ischemia and ischemia-reperfusion injury are primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model simulating the retinal ischemic process has hampered progress in developing neuroprotective agents for RAO. A unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model was developed by employing silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine ischemia duration. Immunofluorescence staining, optical coherence tomography, and hematoxylin and eosin staining were utilized to assess changes in major classes of neural cells and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply seen in RAO. 60-minute ischemia was confirmed to lead the major retinal neural cells loss and visual function impairment. Notable thinning of the inner layer of the retina, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during non-reperfusion and reperfusion periods. The resident microglia within the retina and peripheral leukocytes which access to the retina were pronounced increased on reperfusion periods. Comparison of differentially expressed genes between the UPOAO and high intraocular pressure models identified specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for the screening of pathogenic genes, promoting further therapeutic research in RAO.

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Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

Wang,

Li,

Feng

et al. 2024

eLife

0

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Acute retinal ischemia and ischemia-reperfusion injury are primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model simulating the retinal ischemic process has hampered progress in developing neuroprotective agents for RAO. A unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model was developed by employing silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine ischemia duration. Immunofluorescence staining, optical coherence tomography, and hematoxylin and eosin staining were utilized to assess changes in major classes of neural cells and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply seen in RAO. 60-minute ischemia was confirmed to lead the major retinal neural cells loss and visual function impairment. Notable thinning of the inner layer of the retina, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during non-reperfusion and reperfusion periods. The resident microglia within the retina and peripheral leukocytes which access to the retina were pronounced increased on reperfusion periods. Comparison of differentially expressed genes between the UPOAO and high intraocular pressure models identified specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for the screening of pathogenic genes, promoting further therapeutic research in RAO.

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Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia–Reperfusion in the Eyes of Sprague Dawley Rats

Cited by 6 publications

References 53 publications

Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats

Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats

Silicone Wire Embolization-induced Acute Retinal Artery Ischemia and Reperfusion Model in Mouse: Gene Expression Provides Insight into Pathological Processes

Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

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