Search Results (8)

A spectrum of neuro-ocular changes has been observed in astronauts during and after prolonged exposure to microgravity on long-duration spaceflights. These changes, collectively referred to as “spaceflight associated neuro-ocular syndrome” (SANS), pose a significant challenge for space agencies as they prepare for future human missions, including a return to the Moon and manned missions to Mars. Optic disc edema, a hallmark feature of SANS, occurs in approximately 70% of astronauts on extended missions. Recent evidence suggests a potential link between poor sleep and the development of optic disc edema in individuals exposed to a spaceflight analog environment, providing critical insights into its underlying pathophysiology. Here, we propose a novel hypothesis: sleep deprivation may increase the risk of microgravity-induced optic disc edema by altering translaminar pressure dynamics and disrupting ocular glymphatic outflow. This perspective offers a new framework for understanding SANS and highlights potential targets to mitigate its risks in the context of human space exploration. Full article

In patients with Alzheimer’s disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice. We examined the expression of Mfsd2a and Aqp4 in the retinas of 4-month-old 5xFAD female mice supplemented with high-dose FO for three weeks. There was a significant increase in Mfsd2a expression in 5xFAD retinas supplemented with FO compared to control 5xFAD mice. Additionally, the increase in Aqp4 expression observed in 4-month-old 5xFAD retinas, indicative of an impaired glymphatic system, was significantly decreased. Simultaneously, Aβ accumulation in 5xFAD retinal blood vessels was reduced following FO supplementation. These findings suggest that high-dose FO supplementation could serve as an adjunct in developing new treatments aimed at improving the regulation of transcytosis or the function of the glymphatic system in the AD retina. Full article

The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic. Full article

Background: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space. Here, we tested whether vitreous haze (VH) can provide novel insights into the relationship between neurodegeneration and the ocular glymphatic system in MS. Methods: This cross-sectional study comprised 315 persons with MS and 87 healthy controls (HCs). VH was quantified from optical coherence tomography (OCT) volume scans. Neurodegeneration was determined on three-dimensional T1 (3DT1) MRI, lesion detection on fluid-attenuated inversion (FLAIR), and layer thickness on OCT. Generalized estimating equations, corrected for age, were used to analyze associations between VH and metrics for neurodegeneration, demographics, and clinical scales. Group differences were determined between mild, moderate, and severe disability. Results: On the group level, VH scores were comparable between MS and control (p = 0.629). In MS, VH scores declined with disease duration (β = −0.009, p = 0.004) and age (β = −0.007, p = 0.001). There was no relation between VH scores and higher age in HCs. In MS patients, VH was related to normalized gray (NGMV, β = 0.001, p = 0.011) and white matter volume (NWMV, β = 0.001, p = 0.003), macular ganglion cell–inner plexiform layer thickness (mGCIPL, β = 0.006, p < 0.001), and peripapillary retinal nerve fiber layer thickness (pRNFL, β = 0.004, p = 0.008). VH was significantly lower in severe compared to mild disability (mean difference −28.86%, p = 0.058). Conclusions: There is a correlation between VH on OCT and disease duration, more severe disability and lower brain volumes in MS. Biologically, these relationships suggest accelerated glymphatic clearance with disease-related atrophy. Full article

Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system. Full article

Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases. Full article

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation. Full article

Lymphatic vessels exert major effects on the maintenance of interstitial fluid homeostasis, immune cell trafficking, lipid absorption, tumor progression and metastasis. Recently, novel functional roles for the lymphatic vasculature have emerged, which can be associated with pathological situations. Among them, lymphatics have been proposed to participate in eye aqueous humor drainage, with potential consequences on intraocular pressure, a main risk factor for progression of glaucoma disease. In this review, after the description of eye fluid dynamics, we provide an update on the data concerning the distribution of ocular lymphatics. Particular attention is given to the results of investigations allowing the three dimensional visualization of the ocular surface vasculature, and to the molecular mechanisms that have been characterized to regulate ocular lymphatic vessel development. The studies concerning the potential role of lymphatics in aqueous humor outflow are reported and discussed. We also considered the novel studies mentioning the existence of an ocular glymphatic system which may have, in connection with lymphatics, important repercussions in retinal clearance and in diseases affecting the eye posterior segment. Some remaining unsolved questions and new directions to explore are proposed to improve the knowledge about both lymphatic and glymphatic system interactions with eye fluid homeostasis. Full article