Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body.

BACKGROUND: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive. RESULTS: In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes. CONCLUSION: Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.

Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as Alzheimer's disease (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways. Here, we specifically highlight ABC transporters involved in the maintenance of brain homeostasis and their implications in its metabolic regulation. We also show new aspects related to ABC transporter function found in less recognized diseases, such as Huntington's disease (HD) and experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis (MS). Understanding both their impact on the physiological regulation of the CNS and their roles in brain diseases holds promise for uncovering new therapeutic options. Further investigations and preclinical studies are warranted to elucidate the complex interplay between glial ABC transporters and physiological brain functions, potentially leading to effective therapeutic interventions also for rare CNS disorders.

Racing performance of Thoroughbred racehorses with suspensory ligament branch desmitis treated with mesenchymal stem cells (2010-2019).

BACKGROUND: Suspensory ligament branch desmitis (SLBD) is a common injury in Thoroughbred racehorses. Orthobiologic treatment of these injuries is a relatively new approach, and there is limited information available on post injury racing performance in racehorses treated with mesenchymal stem cells (MSCs). OBJECTIVES: To assess racing performance post injury in Thoroughbred racehorses with SLBD treated with MSCs. STUDY DESIGN: Retrospective case series. METHODS: Medical records of racehorses with SLBD treated with MSCs from 2010 to 2019 were reviewed. All horses were treated with allogeneic stem cells injected locally at the time of diagnosis and subsequently received 3-4 treatments with autologous bone-marrow derived MSCs. Ultrasonographic and radiographic images were evaluated to determine the degree of suspensory branch injury and sesamoiditis of the associated proximal sesamoid bone. Race performance was assessed by career length, class of races, number of starts and earnings post injury. Race performance of horses that raced pre and post injury were compared. RESULTS: Of 69 treated horses, 71% (49/69) [95% CI: 59%-81%] raced post injury. Horses that had raced pre injury were more likely to race post injury (90% [18/20]) than horses that did not race pre injury (63% [31/49]; p = 0.03). Females were less likely to race post injury than males (52% [11/21] vs. 79% [38/49], respectively; p = 0.02). In the 18 horses that raced pre and post injury, the number of races, earnings and earnings per start were not significantly different pre and post injury. The average career length of all horses that raced post injury was 29.5 months. MAIN LIMITATIONS: Retrospective study design and lack of controls. CONCLUSIONS: Treatment with MSCs resulted in a majority of Thoroughbred racehorses with SLBD racing post treatment. Racing pre injury and being male was positively associated with racing post injury.