Choroidal Mast Cells in Retinal Pathology

Bousquet, Elodie; Zhao, Min; Thillaye-Goldenberg, B.; Lorena, Viera; Castañeda, Beatriz; Naud, Marie Christine; Bergin, Ciara; Besson-Lescure, Bernadette; Kozak, Y. de

doi:10.1016/j.ajpath.2015.04.002

Cited by 19 publications

(6 citation statements)

References 46 publications

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“…Whether or not H. pylori plays a role in CSR, the activation and degranulation of mast cells that are resident within the choriocapillaris may be a reasonable connection with other known associations of CSR such as stress or low-dose (not high-dose) steroid exposure and OSA, which can also modulate the immune system and trigger mast cell degranulation. This hypothesis that CSR may be driven and triggered by mast cell accumulation and degranulation, as well as local inflammation, would also be consistent with the purported role of mast cell accumulation and activation in floppy eyelid syndrome [163].…”

Section: Choroidal Layersupporting

confidence: 78%

The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment

Ahn

Gorin²

2021

Curr Sleep Medicine Rep

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Purpose of Review Obstructive sleep apnea (OSA) patients are at significantly increased risks for cardiovascular and cerebrovascular morbidities. Recently, there has been heightened interest in the association of OSA with numerous ocular diseases and possible improvement of these conditions with the initiation of OSA treatment. We reviewed the current evidence with an emphasis on the overlapping pathogeneses of both diseases. Recent Findings Currently available literature points to a substantial association of OSA with ocular diseases, ranging from those involving the eyelid to optic neuropathies and retinal vascular diseases. Since the retina is one of the highest oxygen-consuming tissues in the body, the intermittent hypoxia and hypercapnia ensuing in OSA can have deleterious effects on ocular function and health. Tissue hypoxia, autonomic dysfunction, microvascular dysfunction, and inflammation all play important roles in the pathogenesis of both OSA and ocular diseases. Whether OSA treatment is capable of reversing the course of associated ocular diseases remains to be determined. It is anticipated that future therapeutic approaches will target the common underlying pathophysiologic mechanisms and promote favorable effects on the treatment of known associated ocular diseases. Summary Emerging evidence supports the association of ocular diseases with untreated OSA. Future studies focusing on whether therapeutic approaches targeting the common pathophysiologic mechanisms will be beneficial for the course of both diseases are warranted.

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Section: Choroidal Layersupporting

confidence: 78%

The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment

Ahn

Gorin²

2021

Curr Sleep Medicine Rep

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“…[27] More recently, Bousquet and associates observed ocular inflammation and increased vascular dilation and permeability in choroidal vessels after inducing degranulation. [10] This is accomplished by the release of chemokines and cytokines that attract and activate macrophages and T-cells [23], which is well documented in cardiovascular disease, atherosclerosis, and aortic aneurysms. [5]…”

Section: Discussionmentioning

confidence: 99%

“…[8 9] Since MCs play a key role in inflammation in other tissues like skin and conjunctiva, MCs may play a role in choroidal inflammation as well. [10] MCs can interact with endothelial cells (ECs) and induce their proliferation through release of heparin, metalloproteinases, and VEGF. [11-13] MCs have the ability to induce angiogenesis and have been demonstrated to be present around Bruch's membrane during both the early and late stages of choroidal neovascularization (CNV) in AMD.…”

Section: Introductionmentioning

confidence: 99%

Increased choroidal mast cells and their degranulation in age-related macular degeneration

et al. 2016

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Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid.

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“…degranulation of choroidal mast cells in rodents resulted in RPE abnormalities and outer retinal barrier breakdown (13), however it is not yet known which of the many proteases, or other choroidal mast cell mediators, are involved (14).…”

Section: Introductionmentioning

confidence: 99%

Retinal Distribution and Extracellular Activity of Granzyme B: A Serine Protease That Degrades Retinal Pigment Epithelial Tight Junctions and Extracellular Matrix Proteins

et al. 2020

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Granzymes are a family of serine proteases first shown to be intracellular initiators of immune-mediated cell death in target pathogenic cells. In addition to its intracellular role, Granzyme B (GzmB) has important extracellular functions in immune regulation and extracellular matrix (ECM) degradation. Verified substrates of extracellular GzmB activity include tight junctional and ECM proteins. Interestingly, little is known about the activity of GzmB in the outer human retina, a tissue in which the degradation of the tight junctional contacts of retinal pigment epithelial (RPE) cells and within the external limiting membrane, as well as remodeling of the ECM in Bruch's membrane, cause the breakdown of the blood-retinal barrier and slowing of metabolite transport between neuroretina and choroidal blood supply. Such pathological changes in outer retina signal early events in the development of age-related macular degeneration (AMD), a multifactorial, chronic inflammatory eye disease. This study is the first to focus on the distribution of GzmB in the outer retina of the healthy and diseased post-mortem human eye. Our results revealed that GzmB is present in RPE and choroidal mast cells. More immunoreactive cells are present in older (>65 years) compared to younger (<55 years) donor eyes, and choroidal immunoreactive cells are more numerous in eyes with choroidal neovascularization (CNV), while RPE immunoreactive cells are more numerous in eyes with soft drusen, an early AMD event. In vitro studies demonstrated that RPE-derived tight junctional and ECM proteins are cleaved by exogenous GzmB stimulation. These results suggest that the increased presence of GzmB immunoreactive cells in outer retina of older (healthy) eyes as well as in diseased eyes with CNV (from AMD) and eyes with soft drusen exacerbate ECM remodeling in the Bruch's membrane and degradation of the blood-retinal barrier. Currently there are no treatments that prevent remodeling of the Bruch's membrane and/or the loss of function of the outer blood-retinal barrier, Matsubara et al. Granzyme B in Outer Retina known to promote early AMD changes, such as drusen deposition, RPE dysfunction and pro-inflammation. Specific inhibitors of GzmB, already in preclinical studies for non-ocular diseases, may provide new strategies to stop these early events associated with the development of AMD.

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Choroidal Mast Cells in Retinal Pathology

Cited by 19 publications

References 46 publications

The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment

The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment

Increased choroidal mast cells and their degranulation in age-related macular degeneration

Retinal Distribution and Extracellular Activity of Granzyme B: A Serine Protease That Degrades Retinal Pigment Epithelial Tight Junctions and Extracellular Matrix Proteins

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